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Sexual dysfunction

2021-07-14T17:00:55Z

ShakibaHassanzadeh:

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}} {{SHA}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

=== Prevalence ===
The US National Health and Social Life Survey (NHSLS) showed that the prevalence of sexual problems among the individuals in the US include:<ref name="pmid10022110">{{cite journal| author=Laumann EO, Paik A, Rosen RC| title=Sexual dysfunction in the United States: prevalence and predictors. | journal=JAMA | year= 1999 | volume= 281 | issue= 6 | pages= 537-44 | pmid=10022110 | doi=10.1001/jama.281.6.537 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022110 }} </ref>

==== Women ====

* The [[prevalence]] of sexual complaints is approximately 43% and the most common problems include:
** [[Desire]] (33%)
** [[Orgasm]] (24%)
** [[Lubrication]] (19%)

==== Men ====

* The [[prevalence]] of sexual complaints is approximately 31% and the most common problems include:
** [[Premature ejaculation]] (21%)
** [[Erectile dysfunction]] (5%)
** Low [[desire]] (5%)

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

*[[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>
*According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]]. Most disorders are diagnosed with persisted symptoms for at least 6 months on least 75% of sexual occassions.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

User:ShakibaHassanzadeh

2021-07-14T16:39:43Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

==Pages Authored/Co-authored==
'''Primary Care Project:'''

[[Sexual dysfunction]]

[[Opioid withdrawal|Opioid Withdrawal]]

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]

User:ShakibaHassanzadeh

2021-07-14T16:39:17Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

==Pages Authored/Co-authored==
'''Primary Care Project:'''
[[Sexual dysfunction]]

[[Opioid withdrawal|Opioid Withdrawal]]

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]

User:ShakibaHassanzadeh

2021-01-19T16:16:10Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

==Pages Authored/Co-authored==
'''Primary Care Project:'''

[[Opioid withdrawal|Opioid Withdrawal]]

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]

User:ShakibaHassanzadeh

2021-01-19T16:15:23Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

==Pages Authored/Co-authored==
'''Primary Care Project:'''

[./Https://www.wikidoc.org/index.php/Opioid%20withdrawal Opioid Withdrawal]

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]

User:ShakibaHassanzadeh

2021-01-19T16:13:58Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

== Pages Authored/Co-authored ==
'''Primary Care Project:'''

[[Opioid Withdrawal]]

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]

Sexual dysfunction

2021-01-06T11:52:00Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

=== Prevalence ===
The US National Health and Social Life Survey (NHSLS) showed that the prevalence of sexual problems among the individuals in the US include:<ref name="pmid10022110">{{cite journal| author=Laumann EO, Paik A, Rosen RC| title=Sexual dysfunction in the United States: prevalence and predictors. | journal=JAMA | year= 1999 | volume= 281 | issue= 6 | pages= 537-44 | pmid=10022110 | doi=10.1001/jama.281.6.537 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022110 }} </ref>

==== Women ====

* The [[prevalence]] of sexual complaints is approximately 43% and the most common problems include:
** [[Desire]] (33%)
** [[Orgasm]] (24%)
** [[Lubrication]] (19%)

==== Men ====

* The [[prevalence]] of sexual complaints is approximately 31% and the most common problems include:
** [[Premature ejaculation]] (21%)
** [[Erectile dysfunction]] (5%)
** Low [[desire]] (5%)

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

*[[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>
*According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]]. Most disorders are diagnosed with persisted symptoms for at least 6 months on least 75% of sexual occassions.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:50:42Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

=== Prevalence ===
The US National Health and Social Life Survey (NHSLS) showed that the prevalence of sexual problems among the individuals in the US include:<ref name="pmid10022110">{{cite journal| author=Laumann EO, Paik A, Rosen RC| title=Sexual dysfunction in the United States: prevalence and predictors. | journal=JAMA | year= 1999 | volume= 281 | issue= 6 | pages= 537-44 | pmid=10022110 | doi=10.1001/jama.281.6.537 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10022110 }} </ref>

==== Women ====

* The [[prevalence]] of sexual complaints are approximately 43% and the most common problems include:
** [[Desire]] (33%)
** [[Orgasm]] (24%)
** [[Lubrication]] (19%)

==== Men ====

* The [[prevalence]] of sexual complaints are approximately 31% and the most common problems include:
** [[Premature ejaculation]] (21%)
** [[Erectile dysfunction]] (5%)
** Low [[desire]] (5%)

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

*[[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>
*According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]]. Most disorders are diagnosed with persisted symptoms for at least 6 months on least 75% of sexual occassions.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:47:04Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

=== Prevalence ===
The US National Health and Social Life Survey (NHSLS) showed that the prevalence of sexual problems among the individuals in the US include:

==== Women ====

* The [[prevalence]] of sexual complaints are approximately 43% and the most common problems include:
** [[Desire]] (33%)
** [[Orgasm]] (24%)
** [[Lubrication]] (19%)

==== Men ====

* The [[prevalence]] of sexual complaints are approximately 31% and the most common problems include:
** [[Premature ejaculation]] (21%)
** [[Erectile dysfunction]] (5%)
** Low [[desire]] (5%)

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

*[[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>
*According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]]. Most disorders are diagnosed with persisted symptoms for at least 6 months on least 75% of sexual occassions.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:28:58Z

ShakibaHassanzadeh: /* Diagnostic Study of Choice */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

* [[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p. ">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>
* According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]]. Most disorders are diagnosed with persisted symptoms for at least 6 months on least 75% of sexual occassions.<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p. ">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:25:03Z

ShakibaHassanzadeh: /* Diagnostic Study of Choice */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*[[Delayed ejaculation]]
*Erectile disorder
*Female [[Orgasmic dysfunction|orgasmic]] disorder
*Female sexual interest/[[arousal]] disorder
*[[Genito-pelvic pain]]/[[penetration disorder]]
*Male [[hypoactive sexual desire disorder]]
*[[Premature ejaculation|Premature (early) ejaculation]]
*[[Substance]]/[[medication]] induced sexual dysfunction
*Other specified sexual dysfunction
*Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

* [[Diagnostic and statistical manual of mental disorders|DSM-5]] is used to diagnose different types of sexual dysfunction.
* According to [[Diagnostic and statistical manual of mental disorders|DSM-5]], sexual dysfunction is a group of [[disorders]] that cause clinical impairment in the ability to respond sexually or experience [[sexual pleasure]].

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:13:37Z

ShakibaHassanzadeh: /* Classification */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p. ">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

* [[Delayed ejaculation]]
* Erectile disorder
* Female [[Orgasmic dysfunction|orgasmic]] disorder
* Female sexual interest/[[arousal]] disorder
* [[Genito-pelvic pain]]/[[penetration disorder]]
* Male [[hypoactive sexual desire disorder]]
* [[Premature ejaculation|Premature (early) ejaculation]]
* [[Substance]]/[[medication]] induced sexual dysfunction
* Other specified sexual dysfunction
* Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:12:40Z

ShakibaHassanzadeh: /* Classification */

__NOTOC__

{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==

*Another medical condition

:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]

*lnterpersonal factors

:*Severe relationship distress

*Nonsexual mental disorders
*Other sexual dysfunctions

:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]

*Substance/medication use<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==

*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

*[[Hypoactive sexual disorder]] (see also [[asexuality]])
*[[Bestiality]]
*[[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
*[[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
*[[Erectile dysfunction|Male erectile disorder]]
*Female orgasmic disorder (see [[Anorgasmia]])
*Male orgasmic disorder (see [[Anorgasmia]])
*[[Premature ejaculation]]
*[[Dyspareunia]]
*[[Vaginismus]]
*[[Secondary sexual dysfunction]]
*[[Paraphilia]]s
*[[Gender identity disorder]]
*[[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====

*Sexual dissatisfaction (non-specific)
*Lack of sexual desire
*[[Anorgasmia]]
*[[Erectile dysfunction|Impotence]]
*[[Sexually transmitted disease]]s
*Delay or absence of [[ejaculation]], despite adequate stimulation
*Inability to control timing of ejaculation
*Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
*Inadequate vaginal lubrication preceding and during intercourse
*Burning pain on the [[vulva]] or in the vagina with contact to those areas
*Unhappiness or confusion related to [[sexual orientation]]
*[[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
*[[Persistent sexual arousal syndrome]]
*[[Post SSRI Sexual Dysfunction]]
*[[Sexual addiction]]
*[[Hypersexuality]]
*[[Female genital cutting]] has occurred more in the USA than previously thought
*[[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====

*[[Infertility]]
*[[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

 

==Overview==

==Historical Perspective==

==Classification==
According to the [[Diagnostic and Statistical Manual of Mental Disorders]] 5 (DSM-5), the list of sexual dysfunctions include:{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

* [[Delayed ejaculation]]
* Erectile disorder
* Female [[Orgasmic dysfunction|orgasmic]] disorder
* Female sexual interest/[[arousal]] disorder
* [[Genito-pelvic pain]]/[[penetration disorder]]
* Male [[hypoactive sexual desire disorder]]
* [[Premature ejaculation|Premature (early) ejaculation]]
* [[Substance]]/[[medication]] induced sexual dysfunction
* Other specified sexual dysfunction
* Unspecified sexual dysfunction.

==Pathophysiology==

==Causes==

==Differentiating Sexual Dysfunction from other Diseases==

==Epidemiology and Demographics==

==Risk Factors==
According to a consensus statement from the 4th International Consultation on Sexual Medicine in 2015, the risk factors of sexual dysfunction include:<ref name="pmid26953830">{{cite journal| author=McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD | display-authors=etal| title=Risk Factors for Sexual Dysfunction Among Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. | journal=J Sex Med | year= 2016 | volume= 13 | issue= 2 | pages= 153-67 | pmid=26953830 | doi=10.1016/j.jsxm.2015.12.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26953830 }} </ref>

====Risk Factors for Women====

*[[Biological]] factors:
**Poor [[health]]
**Lower levels of physical activities
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Hypertension]]
**[[Antihypertensive drugs]]
**[[Chronic diseases]]:
***[[Hyperthyroidism]], [[hypothyroidism]], and [[thyroid disease]]
***[[Fibromyalgia]]
***[[Arthritis]]
***[[Multiple sclerosis]]
***[[Systemic sclerosis]]
***[[Spinal cord injury]]
***[[Metabolic syndrome]]
***Untreated [[obstructive sleep apnea]]
**Stress [[urinary incontinence]]
**[[Urinary tract]] symptoms
**[[Hysterectomy]]
**Female genital mutilation or cutting
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Mood Disorder|Mood]] or [[anxiety disorders]]
**[[Antidepressants]]
**[[Schizophrenia]]
**[[Antipsychotic drugs]]
*Sociocultural factors:
**History of [[sexual abuse]]
**Emotional and [[physical abuse]] during childhood
**Sexual dysfunctions in the male partner
**Low education
**[[Stress]] at work or unemployment
**[[Substance abuse]] ([[alcohol]], [[tobacco]], and [[opioids]])

====Risk Factors For Men====

*[[Biology|Biological]] factors:
**Poor [[health]]
**Age
**[[Diabetes mellitus|Diabetes Mellitus (DM)]]
**[[Obesity]], [[metabolic syndrome]], and [[Erectile dysfunction|erectile dysfunction (ED)]]
**[[Cardiovascular disease]] and [[hypertension]]
**[[Smoking]] or other [[tobacco]] use
**[[Hormone|Hormonal]] or [[endocrine]] factors
**[[Urinary tract]] diseases and lower [[urinary tract]] symptoms
**Other [[chronic diseases]]:
***[[Polyneuropathy]]
***[[Parkinson disease]]
***[[Multiple sclerosis]]
***[[Anxiety]] and [[depression]]
***[[Spinal cord injury]]
***[[Sleep apnea]]
***[[Chronic obstructive pulmonary disease|Chronic obstructive pulmonary disease (COPD)]]
***[[Scleroderma]]
***[[Hypertension]]
**[[Surgery]] and [[trauma]]:
***[[Spinal cord injury]]
***[[Radical prostatectomy]] for [[prostate cancer]]
*[[Psychology|Psychological]] and [[psychiatric]] factors:
**[[Medication|Medications]] and [[recreational drugs]]:
***[[Cardiovascular]], [[hormonal]], [[anticholinergic]], [[cytotoxic]], and [[Psychotropic drugs|psychotropic]] drugs
***[[Alcohol]], [[marijuana]], and [[narcotics]]
**[[Anxiety]] and [[depression]]
*Sociocultural factors:
**Early childhood experiences
**Lack of physical activity
**Not being married
**[[Sexual]] problems in the partner
**Unemployment
**Lower level of education

==Screening==

==Natural History, Complications, and Prognosis==

==Diagnosis==

===Diagnostic Study of Choice===

===History and Symptoms===

===Physical Examination===

===Physical Examination===

===Electrocardiogram===

===X-ray===

===Echocardiography or Ultrasound===

===CT scan===

===MRI===

===Other Imaging Findings===

===Other Diagnostic Studies===

==Treatment==

===Medical Therapy===

===Surgery===

===Primary Prevention===

===Secondary Prevention===

==See also==

*[[Sexual function]] for information about assessing sexual dysfunction
*[[Sexual arousal disorder]]
*[[Female sexual arousal disorder]]
*[[Post SSRI Sexual Dysfunction]]
*[[Agony aunt]]
*[[Anorgasmia]]
*[[Premature ejaculation]]
*[[Dapoxetine]]
*[[Sexless marriage]]

==References==
{{reflist|2}}

==Further reading==

*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==

*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Sexual dysfunction

2021-01-06T11:12:23Z

ShakibaHassanzadeh:

Sexual dysfunction

2021-01-05T15:46:06Z

ShakibaHassanzadeh: /* Risk Factors */

Sexual dysfunction

2021-01-05T15:42:53Z

ShakibaHassanzadeh:

Sexual dysfunction

2021-01-05T14:48:02Z

ShakibaHassanzadeh:

Sexual dysfunction

2021-01-05T14:47:08Z

ShakibaHassanzadeh:

__NOTOC__
{{DiseaseDisorder infobox |
Name = Sexual dysfunction |
ICD10 = F52 |
ICD9 = {{ICD9|302.7}} |
}}
{{SI}}
{{CMG}}; {{AE}} {{KS}}

==Overview==

'''Sexual dysfunction''' or '''sexual malfunction''' (see also [[sexual function]]) is difficulty during any stage of the [[sexual act]] (which includes [[Interpersonal attraction|desire]], [[sexual arousal|arousal]], [[orgasm]], and resolution) that prevents the individual or couple from enjoying sexual activity.

==Onset==
Emotional factors affecting sex include both interpersonal problems (such as marital/relationship problems, or lack of trust and open communication between partners) and psychological problems within the individual ([[clinical depression|depression]], sexual fears or guilt, past sexual trauma, sexual disorders,<ref name="Michetti_et_al_2006">{{cite journal | last = Michetti | first = Paolo Maria | coauthors = Roberta Rossi, Daniele Bonanno, Andrea Tiesi and Chiara Simonelli | year = 2006 | title = Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED) | journal = International Journal of Impotence Research | volume = 18 | issue = 2 | pages = 170–174 | id = {{PMID|16151475}} | url = http://www.nature.com/ijir/journal/v18/n2/full/3901386a.html | accessdate = 2007-02-02}}</ref> and so on).

Physical factors include drugs (alcohol, [[nicotine]], [[narcotic]]s, stimulants, antihypertensives, [[antihistamine]]s, and some psychotherapeutic drugs); injuries to the back, problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries); or disease ([[diabetic neuropathy]], [[multiple sclerosis]], [[tumor]]s, and, rarely, tertiary [[syphilis]]); failure of various organ systems (such as the heart and lungs); [[endocrine]] disorders ([[thyroid]], [[pituitary]], or [[adrenal gland]] problems); hormonal deficiencies (low [[testosterone]], [[estrogen]], or [[androgen]]s); and some [[birth defect]]s.

==Classification==

Sexual dysfunction disorders are generally classified into four categories: sexual desire disorders, sexual arousal disorders, orgasm disorders, and sexual pain disorders.

#Sexual desire disorders or decreased libido can be caused by a decrease in normal estrogen (in women) or testosterone (in both men and women) production. Other causes may be aging, fatigue, pregnancy, medications (such as the [[selective serotonin reuptake inhibitor|SSRIs]]) or psychiatric conditions, such as depression and anxiety. Loss of [[libido]] from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This is known as [[PSSD]].
#Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal. For both men and women, these conditions can manifest as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity. There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. As the success of [[sildenafil]] (Viagra) attests, most erectile disorders in men are primarily physical, not psychological conditions.
#Orgasm disorders are a persistent delay or absence of orgasm following a normal sexual excitement phase. The disorder can occur in both women and men. Again, the [[SSRI]] antidepressants are frequent culprits -- these can delay the achievement of orgasm or eliminate it entirely.
#Sexual pain disorders affect women almost exclusively and are known as [[dyspareunia]] (painful intercourse) and [[vaginismus]] (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse). Dyspareunia may be caused by insufficient lubrication ([[vaginal dryness]]) in women.

Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by [[menopause]], [[pregnancy]], or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called [[vulvodynia]] or [[vulvar vestibulitis]]. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Sexual dysfunctions are more common in the early adult years, with the majority of people seeking care for such conditions during their late twenties through thirties. The incidence increases again in the geriatric population, typically with gradual onset of symptoms that are associated most commonly with medical causes of sexual dysfunction.

Sexual dysfunction is more common in people who abuse alcohol and drugs. It is also more likely in people suffering from diabetes and degenerative neurological disorders. Ongoing psychological problems, difficulty maintaining relationships or chronic disharmony with the current sexual partner can also interfere with [[sexual function]].

==Differential Diagnosis of Male Hypoactive Sexual Desire Disorder==
*Another medical condition
:*Central nervous system disease
:*[[Diabetes mellitus]]
:*[[Hypogonadism]]
:*[[Thyroid disease|Thyroid dysfunction]]
*lnterpersonal factors
:*Severe relationship distress
*Nonsexual mental disorders
*Other sexual dysfunctions
:*[[Premature ejaculation|Early ejaculation]]
:*[[Erectile dysfunction|Erectile difficulties]]
*Substance/medication use<ref name=DSMV>{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors of Male Hypoactive Sexual Desire Disorder==
*Age
*Attitudes
*[[Alcohol]]
*[[Anxiety]]
*Emotional connection
*[[Hypogonadism]]
*[[Hyperprolactinemia]]
*Interpersonal problems
*Lack of adequate sex education
*Mood
*Man's feelings about himself
*Partner's sexual desire
*Social and cultural contextual factors
*Trauma from early life experiences<ref name=DSMV>{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Diagnosis==
===Symptoms===
====Psychological sexual disorders====
The fourth edition of the [[Diagnostic and Statistical Manual of Mental Disorders]] lists the following psychological sexual disorders:

* [[Hypoactive sexual disorder]] (see also [[asexuality]])
* [[Bestiality]]
* [[Sexual aversion disorder]] (avoidance of or lack of desire for sexual intercourse)
* [[Female sexual arousal disorder]] (failure of normal lubricating arousal response)
* [[Erectile dysfunction|Male erectile disorder]]
* Female orgasmic disorder (see [[Anorgasmia]])
* Male orgasmic disorder (see [[Anorgasmia]])
* [[Premature ejaculation]]
* [[Dyspareunia]]
* [[Vaginismus]]
* [[Secondary sexual dysfunction]]
* [[Paraphilia]]s
* [[Gender identity disorder]]
* [[PTSD]] due to genital mutilation or childhood sexual abuse

====Other sexual problems====
* Sexual dissatisfaction (non-specific)
* Lack of sexual desire
* [[Anorgasmia]]
* [[Erectile dysfunction|Impotence]]
* [[Sexually transmitted disease]]s
* Delay or absence of [[ejaculation]], despite adequate stimulation
* Inability to control timing of ejaculation
* Inability to relax [[vagina]]l muscles enough to allow [[intercourse]]
* Inadequate vaginal lubrication preceding and during intercourse
* Burning pain on the [[vulva]] or in the vagina with contact to those areas
* Unhappiness or confusion related to [[sexual orientation]]
* [[Transsexual]] and [[transgender]] people may have sexual problems (before or after [[sex reassignment surgery|surgery]]), though actually being transgendered or transsexual is not a sexual problem in itself.
* [[Persistent sexual arousal syndrome]]
* [[Post SSRI Sexual Dysfunction]]
* [[Sexual addiction]]
* [[Hypersexuality]]
* [[Female genital cutting]] has occurred more in the USA than previously thought
* [[Male circumcision]] alters the natural sexual function for both partners

====Other related problems====
* [[Infertility]]
* [[Paraphilia]]

==Diagnostic Criteria==
===DSM-V Diagnostic Criteria for Male Hypoactive Sexual Desire Disorder <ref name=DSMV>{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>===
{{cquote|

*A. Persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity. The judgment of deficiency is made by the clinician, taking into account factors that affect sexual functioning, such as age and general and socio cultural contexts of the individual’s life.

'''''AND'''''

*B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months.

'''''AND'''''
*C. The symptoms in Criterion A cause clinically significant distress in the individual.

'''''AND'''''

*D. The sexual dysfunction is not better explained by a nonsexual mental disorder or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
 
Specify whether:

*Lifelong: The disturbance has been present since the Individual became sexually active.

*Acquired; The disturbance began after a period of relatively normal sexual function.

Specify whether:

*Generaiized: Not limited to certain types of stimulation, situations, or partners.

*Situational: Only occurs with certain types of stimulation, situations, or partners.

Specify current severity:

*Mild: Evidence of mild distress over the symptoms in Criterion A.

*Moderate: Evidence of moderate distress over the symptoms In Criterion A.

*Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
}}

==Clinical studies==
Since people tend not to talk to one another about their sexual problems, many people imagine that they are "abnormal", or that their sexual problems are unique or [[shame]]ful. Images of sexuality presented by [[society]] and the [[mass media|media]] often present people with unrealistic ideals of sexual behavior, whether of the ideals of [[chastity]] and sexual fidelity presented by [[religion]], or the ideal of sexual inexhaustibility and [[promiscuity|promiscuous]] availability presented by [[pornography]]. Neither image appears to be representative of human behavior in real life: this has been summed up in the phrase ''"everyone lies about sex"''.

The earliest attempts at treating sexual dysfunctions, especially [[erectile dysfunction]], date back to [[Islamic medicine|Muslim physicians and pharmacists]] in the [[Islamic Golden Age|medieval Islamic world]]. They were the first to prescribe [[medication]] for the treatment of this problem, and they developed several methods of [[therapy]] for this issue, including a single-drug therapy method where a [[drug]] was prescribed and a "combination method of either a drug or [[food]]." Most of these drugs were oral medication, though a few patients were also treated through [[topical]] and [[Transurethral resection of the prostate|transurethral]] means. Sexual dysfunctions were being treated with clinically [[Drug test|tested drugs]] in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including [[Muhammad ibn Zakarīya Rāzi]], [[Thabit bin Qurra]], [[Ibn Al-Jazzar]], [[Avicenna]] (''[[The Canon of Medicine]]''), [[Averroes]], [[Ibn al-Baitar]], and [[Ibn al-Nafis]] (''The Comprehensive Book on Medicine'').<ref>A. Al Dayela and N. al-Zuhair (2006), "Single drug therapy in the treatment of male sexual/erectile dysfunction in Islamic medicine", ''Urology'' '''68''' (1), p. 253-254.</ref>

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when [[William Masters and Virginia Johnson|Masters and Johnson's]] ''[[Human Sexual Inadequacy]]'' was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier ''[[Human Sexual Response]]'' (1966).

Prior to Masters and Johnson the clinical approach to sexual problems was largely derived from the thinking of [[Freud]]. It was held with [[psychopathology]] and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise and the diagnostic approach was from the psychopathological. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into [[frigidity]] or [[Erectile dysfunction|impotence]], terms which too soon acquired negative connotations in popular culture.

The achievement of ''Human Sexual Inadequacy'' was to move thinking from psychopathology to ''learning'', only if a problem did not respond to educative treatment would psychopathological problems be considered. Also treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties and vice versa.

The basic Masters and Johnson treatment program was an intensive two week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experience by the majority of people, dysfunctions bounded male primary or secondary [[Erectile dysfunction|impotence]], [[premature ejaculation]], [[ejaculatory incompetence]]; female primary [[orgasmic dysfunction]] and situational orgasmic dysfunction; pain during intercourse ([[dyspareunia]]) and [[vaginismus]]. According to Masters and Johnson [[sexual arousal]] and [[orgasm|climax]] are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly over-run by ethusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

==Overview==

==Historical Perspective==
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].

==Classification==
There is no established system for the classification of [disease name].

OR

[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].

OR

[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].

OR

Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

If the staging system involves specific and characteristic findings and features:
According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

The staging of [malignancy name] is based on the [staging system].

OR

There is no established system for the staging of [malignancy name].

==Pathophysiology==
The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

==Causes==
Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].

==Differentiating ((Page name)) from other Diseases==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.

OR

In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

OR

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.

Patients of all age groups may develop [disease name].

OR

The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.

OR

[Disease name] commonly affects individuals younger than/older than [number of years] years of age.

OR

[Chronic disease name] is usually first diagnosed among [age group].

OR

[Acute disease name] commonly affects [age group].

There is no racial predilection to [disease name].

OR

[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

[Disease name] affects men and women equally.

OR

[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

The majority of [disease name] cases are reported in [geographical region].

OR

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

==Risk Factors==
There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

==Diagnosis==
===Diagnostic Study of Choice===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

===Electrocardiogram===
There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

===X-ray===
There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

===CT scan===
There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

===MRI===
There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

===Other Imaging Findings===
There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

==Treatment==
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR

The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

===Surgery===
Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

===Primary Prevention===
There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

==See also==
* [[Sexual function]] for information about assessing sexual dysfunction
* [[Sexual arousal disorder]]
* [[Female sexual arousal disorder]]
* [[Post SSRI Sexual Dysfunction]]
* [[Agony aunt]]
* [[Anorgasmia]]
* [[Premature ejaculation]]
* [[Dapoxetine]]
* [[Sexless marriage]]

==References==
{{reflist|2}}

== Further reading ==
*Kaplan, Helen Singer, ''The New Sex Therapy: Active Treatment Of Sexual Dysfunctions'', New York, Brunner/Mazel, 1974. ISBN 0876300832

==External links==
*[http://www.nlm.nih.gov/medlineplus/ency/article/001951.htm NIH site on sexual problems]
*[https://web4health.info/eu/kom/sex-menu.htm 100 FAQs about sexual dysfunction]
*[http://www.vaginismus-awareness-network.co.uk/index.html Vaginimus Awareness Network: A non-profit site offering facts and advice to women with vaginismus, their partners and gynaecologists]
*[http://recover.forumup.org Sexual Dysfunction Research Community ]
*[http://www.healthystrokes.com Traumatic Masturbatory Syndrome and other masturbation issues]
*[http://www.sexhealthmatters.org/index.html Sexual Medicine Society of North America's website: SexHealthMatters.org]
*[http://www.psas.nl Persistent Sexual Arousal Syndrome - Language: Dutch and English]
*[http://www.premature-ejaculation-selfhelp.com Premature Ejaculation] Self Help Treatment
*[http://www.sexuality-encyclopedia.com/dr-ruth/index.php?title=Sexual_Dysfunction%2C_Male Dr. Ruth Westheimer on male sexual dysfunction]

{{Mental and behavioural disorders}}

[[Category:Sexual health]]
[[Category:Sexual arousal]]
[[Category:Orgasm]]

[[bs:Poremećaji seksualnog nagona]]
[[ca:Disfunció sexual]]
[[de:Sexuelle Dysfunktion]]
[[es:Disfunción sexual]]
[[is:Kynlífsraskanir]]
[[pl:Dysfunkcja seksualna]]
[[zh:性冷感]]

{{jb1}}
{{WH}}
{{WS}}

Opioid withdrawal

2020-12-21T16:53:03Z

ShakibaHassanzadeh: /* DSM-V Diagnostic Criteria for Opioid Withdrawal{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }} */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use or may be precipitated by the administration of an [[opioid antagonist]] in an individual with prolonged [[opioid]] use or by the administration of an [[opioid]] [[partial agonist]] in an individual that is currently using a full [[opioid]] [[agonist]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal [[symptoms]] may occur with:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*Discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use.
*Precipitation by administrating of an [[opioid antagonist]] (such as [[naloxone]] or [[naltrexone]]) to an individual with prolonged [[opioid]] use.
*Precipitation by administrating of an [[opioid]] [[partial agonist]] (such as [[buprenorphine]]) to an individual that is currently using a full [[opioid]] [[agonist]].

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) [[opioid]] use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an [[opioid antagonist]] after a period of [[opioid]] use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. [[Dysphoric]] mood
:*2. [[Nausea]] or [[vomiting]]
:*3. [[Muscle aches]]
:*4. [[Lacrimation]] or [[rhinorrhea]]
:*5. [[Pupillary dilation]], [[piloerection]], or [[sweating]]
:*6. [[Diarrhea]]
:*7. [[Yawning]]
:*8. [[Fever]]
:*9.[[Insomnia]]

'''''AND'''''

*C. The [[signs]] or [[symptoms]] in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The [[signs]] or [[symptoms]] are not attributable to another medical condition and are not better explained by another [[mental disorder]], including [[intoxication]] or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:50:15Z

ShakibaHassanzadeh: /* Overview */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use or may be precipitated by the administration of an [[opioid antagonist]] in an individual with prolonged [[opioid]] use or by the administration of an [[opioid]] [[partial agonist]] in an individual that is currently using a full [[opioid]] [[agonist]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal [[symptoms]] may occur with:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p.">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

*Discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use.
*Precipitation by administrating of an [[opioid antagonist]] (such as [[naloxone]] or [[naltrexone]]) to an individual with prolonged [[opioid]] use.
*Precipitation by administrating of an [[opioid]] [[partial agonist]] (such as [[buprenorphine]]) to an individual that is currently using a full [[opioid]] [[agonist]].

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:45:20Z

ShakibaHassanzadeh: /* Causes */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the cessation of [[Opioid|opioids]] or the administration of an [[opioid antagonist]] following a heavy or prolonged use of [[Opioid|opioids]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal [[symptoms]] may occur with:<ref name="Diagnostic and statistical manual of mental disorders : DSM-5 2013 p. ">{{cite book | title=Diagnostic and statistical manual of mental disorders : DSM-5 | publisher=American Psychiatric Association,American Psychiatric Association | publication-place=Arlington, VA Washington, D.C | year=2013 | isbn=0-89042-555-8 | oclc=830807378 | page=}}</ref>

* Discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use.
* Precipitation by administrating of an [[opioid antagonist]] (such as [[naloxone]] or [[naltrexone]]) to an individual wiht prolonged [[opioid]] use.
* Precipitation by administrating of an [[opioid]] [[partial agonist]] (such as [[buprenorphine]]) to an individual that is currently using a full [[opioid]] [[agonist]].

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:40:51Z

ShakibaHassanzadeh: /* Causes */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the cessation of [[Opioid|opioids]] or the administration of an [[opioid antagonist]] following a heavy or prolonged use of [[Opioid|opioids]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==

*[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*Abrupt discontinuation or reduction of [[opioid]] use in [[opioid]] dependent users may lead to severe withdrawal symptoms.<ref name="pmid31215431">{{cite journal| author=Nuamah JK, Sasangohar F, Erraguntla M, Mehta RK| title=The past, present and future of opioid withdrawal assessment: a scoping review of scales and technologies. | journal=BMC Med Inform Decis Mak | year= 2019 | volume= 19 | issue= 1 | pages= 113 | pmid=31215431 | doi=10.1186/s12911-019-0834-8 | pmc=6580513 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31215431 }} </ref>

* Discontinuation or reduction of [[opioid]] use in individuals with heavy and prolonged [[opioid]] use.
* May be precipitated by the administration of an [[opioid antagonist]] (such as [[naloxone]] or [[naltrexone]]) to an individual wiht prolonged [[opioid]] use.
* May be precipitated by the administration of an [[opioid]] [[partial agonist]] (such as [[buprenorphine]]) to an individual that is currently using a full [[opioid]] [[agonist]].

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:28:31Z

ShakibaHassanzadeh: /* Causes */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the cessation of [[Opioid|opioids]] or the administration of an [[opioid antagonist]] following a heavy or prolonged use of [[Opioid|opioids]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
* [[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
* Abrupt discontinuation or reduction of [[opioid]] use in [[opioid]] dependent users may lead to severe withdrawal symptoms.<ref name="pmid31215431">{{cite journal| author=Nuamah JK, Sasangohar F, Erraguntla M, Mehta RK| title=The past, present and future of opioid withdrawal assessment: a scoping review of scales and technologies. | journal=BMC Med Inform Decis Mak | year= 2019 | volume= 19 | issue= 1 | pages= 113 | pmid=31215431 | doi=10.1186/s12911-019-0834-8 | pmc=6580513 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31215431 }} </ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:21:30Z

ShakibaHassanzadeh:

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{SHA}}, {{KS}}

==Overview==
[[Opioid]] withdrawal occurs due to the cessation of [[Opioid|opioids]] or the administration of an [[opioid antagonist]] following a heavy or prolonged use of [[Opioid|opioids]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:21:05Z

ShakibaHassanzadeh: /* Overview */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
[[Opioid]] withdrawal occurs due to the cessation of [[Opioid|opioids]] or the administration of an [[opioid antagonist]] following a heavy or prolonged use of [[Opioid|opioids]]. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], [[anxiety]], [[irritability]], [[leg cramps]], [[abdominal cramps]], [[Vomiting|nausea, vomiting]], [[diarrhea]], [[insomnia]], [[pain]], [[tremor]], [[rhinorrhea]], [[sweating]], and cravings for the [[medication|drug]] itself. Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days, however, many patients require appropriate [[treatment]]. The DSM-V Diagnostic Criteria is used for the [[diagnosis]] of [[opioid]] withdrawal. The [[Medication|medications]] for treatment include [[Methadone]], [[clonidine]], [[Buprenorphine]], and adjunctive [[drugs]].

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==

*The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
*In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
*About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive [[drugs]] for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

*[[Lofexidine]]
**Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
**[[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T16:10:21Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
* The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>
* In the USA, the amount of [[opioids]] prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.<ref name="pmid24310049">{{cite journal| author=Sites BD, Beach ML, Davis MA| title=Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users. | journal=Reg Anesth Pain Med | year= 2014 | volume= 39 | issue= 1 | pages= 6-12 | pmid=24310049 | doi=10.1097/AAP.0000000000000022 | pmc=3955827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24310049 }} </ref>
* About 4% of adults in the USA regularly use [[opioids]] for [[pain]].<ref name="pmid27028915">{{cite journal| author=Volkow ND, McLellan AT| title=Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies. | journal=N Engl J Med | year= 2016 | volume= 374 | issue= 13 | pages= 1253-63 | pmid=27028915 | doi=10.1056/NEJMra1507771 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27028915 }} </ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

* [[Lofexidine]]
** Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
** [[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:58:33Z

ShakibaHassanzadeh: /* Medical Therapy */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

* [[Lofexidine]]
** Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
** [[Lofexidine]] is an α-[[adrenergic agonist]]<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:58:12Z

ShakibaHassanzadeh: /* Treatment */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

*Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
*Opiate Craving Scale (OCS)
*Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

* [[Lofexidine]]
** Has been approved in the United Kingdom for treatment of [[opioid]] withdrawal since 1992
** [[Lofexidine]] is an α-[[adrenergic agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:51:58Z

ShakibaHassanzadeh: /* Other Diagnostic Studies */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:<ref name="pmid30724094">{{cite journal| author=Doughty B, Morgenson D, Brooks T| title=Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. | journal=Ann Pharmacother | year= 2019 | volume= 53 | issue= 7 | pages= 746-753 | pmid=30724094 | doi=10.1177/1060028019828954 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30724094 }} </ref>

* Short Opioid Withdrawal Scale (SOWS)<ref name="pmid2248123">{{cite journal| author=Gossop M| title=The development of a Short Opiate Withdrawal Scale (SOWS). | journal=Addict Behav | year= 1990 | volume= 15 | issue= 5 | pages= 487-90 | pmid=2248123 | doi=10.1016/0306-4603(90)90036-w | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2248123 }} </ref><ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
* Objective Opiate Withdrawal Scale (OOWS)<ref name="pmid3687892">{{cite journal| author=Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD| title=Two new rating scales for opiate withdrawal. | journal=Am J Drug Alcohol Abuse | year= 1987 | volume= 13 | issue= 3 | pages= 293-308 | pmid=3687892 | doi=10.3109/00952998709001515 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3687892 }} </ref>
* Opiate Craving Scale (OCS)
* Opiate Withdrawal Scale (OWS)

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:48:23Z

ShakibaHassanzadeh: /* Other Diagnostic Studies */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

*Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
*However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
*Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
**Emergence of [[pain]]
**Exacerbation of a preexisting [[pain]]
**Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
Several scales are used in [[opioid]] withdrawal syndrome including:

* Short Opioid Withdrawal Scale (SOWS),4,5
* Objective Opiate Withdrawal Scale (OOWS),5
* Opiate Craving Scale (OCS),6
* Opiate Withdrawal Scale (OWS).7

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*[[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
*[[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
*Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
*Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:30:09Z

ShakibaHassanzadeh: /* Natural History, Complications and Prognosis */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

* Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days.
* However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use.<ref name="pmid24500948">{{cite journal| author=Mattick RP, Breen C, Kimber J, Davoli M| title=Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. | journal=Cochrane Database Syst Rev | year= 2014 | volume= | issue= 2 | pages= CD002207 | pmid=24500948 | doi=10.1002/14651858.CD002207.pub4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24500948 }} </ref><ref name="pmid29396985">{{cite journal| author=Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE | display-authors=etal| title=Extended-release injectable naltrexone for opioid use disorder: a systematic review. | journal=Addiction | year= 2018 | volume= 113 | issue= 7 | pages= 1188-1209 | pmid=29396985 | doi=10.1111/add.14180 | pmc=5993595 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29396985 }} </ref>
* Potential [[complications]] of discontinuing [[opioid]] use may include:<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
** Emergence of [[pain]]
** Exacerbation of a preexisting [[pain]]
** Requirement of higher doses of [[opioid]] to manage [[pain]]

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
here are no other [[diagnostic]] studies associated with [[opioid]] withdrawal.

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

* Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
* [[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
* [[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
* Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
* Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:20:43Z

ShakibaHassanzadeh: /* Prevention */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

* Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days. However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use. 15,16
*

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
here are no other [[diagnostic]] studies associated with [[opioid]] withdrawal.

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

* Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
* [[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
* [[Opioid]] tapering (gradual reduction in [[opioid]] dose)<ref name="pmid29125396">{{cite journal| author=Burma NE, Kwok CH, Trang T| title=Therapies and mechanisms of opioid withdrawal. | journal=Pain Manag | year= 2017 | volume= 7 | issue= 6 | pages= 455-459 | pmid=29125396 | doi=10.2217/pmt-2017-0028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29125396 }} </ref>
* Early [[diagnosis]] and [[treatment]] of [[opioid]] use dependence.
* Long-term treatment of [[opioid]] use dependence.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T15:17:12Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
***[[Opioid]] craving, compulsive use, and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
**Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
***[[Physical dependence]] symptoms

===Locus coeruleus (LC)===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

*Has [[Norepinephrine|norepinephrine (NE)]] neurons
*Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
*Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

*[[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
**Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Natural History, Complications and Prognosis==

* Depending on the [[opioid]]'s [[half-life]], the [[Symptom|symptoms]] of [[opioid]] withdrawal usually resolve within 5 to 14 days. However, many patients require appropriate [[treatment]] since the [[Symptom|symptoms]] and distress is severe in the first days after the cessation of [[opioid]] use. 15,16
*

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
here are no other [[diagnostic]] studies associated with [[opioid]] withdrawal.

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Prevention===

* Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
* [[Opioid]] replacement therapy (replace short-acting [[Opioid|opioids]] with long-acting [[Opioid|opioids]]).
* [[Opioid]] tapering (gradual reduction in [[opioid]] dose)
*

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T14:50:59Z

ShakibaHassanzadeh: /* Pathophysiology */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different [[organs]] and these may be the underlying [[pathophysiology]] of [[opioid]] withdrawal symptoms, such as:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

* [[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
** Mu opioid receptors:
*** [[Diarrhea]], [[nausea and vomiting]]
* [[Brain]]:
** [[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
*** [[Opioid]] craving, compulsive use, and [[depression]]
** Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
*** [[Insomnia]]
** Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]):
*** [[Physical dependence]] symptoms </blockquote>

=== Locus coeruleus (LC) ===
[[Locus ceruleus|Locus ceruleus(LC)]]:<ref name="pmid22762025">{{cite journal| author=Mazei-Robison MS, Nestler EJ| title=Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons. | journal=Cold Spring Harb Perspect Med | year= 2012 | volume= 2 | issue= 7 | pages= a012070 | pmid=22762025 | doi=10.1101/cshperspect.a012070 | pmc=3385942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22762025 }} </ref>

* Has [[Norepinephrine|norepinephrine (NE)]] neurons
* Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
* Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

* [[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
* Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:
** Inhibition of the [[enzymes]] in the [[cAMP]] pathway
** Decreased firing rate of [[Locus ceruleus|LC]] neurons
** Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

* [[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
** Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons:<ref name="pmid18567959">{{cite journal| author=Kosten TR, George TP| title=The neurobiology of opioid dependence: implications for treatment. | journal=Sci Pract Perspect | year= 2002 | volume= 1 | issue= 1 | pages= 13-20 | pmid=18567959 | doi=10.1151/spp021113 | pmc=2851054 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18567959 }} </ref><ref name="pmid20837544">{{cite journal| author=Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC | display-authors=etal| title=Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons. | journal=Proc Natl Acad Sci U S A | year= 2010 | volume= 107 | issue= 39 | pages= 17011-6 | pmid=20837544 | doi=10.1073/pnas.1010077107 | pmc=2947876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20837544 }} </ref>

* Hyperactivation of [[Locus ceruleus|LC]]
* Increased production of [[cAMP]]
* Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Screening==

==Natural History, Complications and Prognosis==
Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days. The user, upon returning to the environment where they usually used opiates, can experience environmentally implied physical withdrawal symptoms well-after regaining physical homeostasis - or the termination of the physical withdrawal phase by synthesis of endogenous opioids (endorphins) and upregulation of [[opioid receptors]] to the effects of normal levels of endogenous opioids. These implied symptoms are often just as distressing and painful as the initial withdrawal phase.

Detoxification is best conducted in an in patient facility that provides a controlled environment. Patients who are isolated and exposed solely to care givers and other patients in this environment have a better rate of staying clean then those who detox out-patient.

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
here are no other [[diagnostic]] studies associated with [[opioid]] withdrawal.

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Primary Prevention===
===Primary Prevention===

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-21T14:43:22Z

ShakibaHassanzadeh: /* `Pathophysiology */

__NOTOC__
{| class="infobox" style="float:right;"
|-
|[[File:Siren.gif|30px|link=Opioid withdrawal resident survival guide]]|| || 
|[[Opioid withdrawal resident survival guide|'''Resident''' '''Survival''' '''Guide''']]
|}
{{Opioid}}
{{CMG}}; {{AE}} {{KS}}, {{SHA}}

==Overview==
Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of [[withdrawal]] from opiates include, but are not limited to, [[clinical depression|depression]], aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the [[medication|drug]] itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

==Historical Perspective==

*[[Opium]] and its derivatives have been used as medical therapies since 5,000 years ago.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the United States, in the early 20th century, [[opiates]] were [[over-the-counter]] drugs and were commonly used in [[medical therapy]] of various disorders.<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>
*In the early 1900s, the federal restrictions on [[opioid]] access caused suffering and death since there were no effective [[treatments]] for the [[opioid]] withdrawal symptoms that happened with sudden discontinuation of [[opioids]].<ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

==Classification==
The onset and duration of [[opioid]] withdrawal depends on the half-life of the consumed [[opioid]]:<ref name="pmid32563380">{{cite journal| author=Srivastava AB, Mariani JJ, Levin FR| title=New directions in the treatment of opioid withdrawal. | journal=Lancet | year= 2020 | volume= 395 | issue= 10241 | pages= 1938-1948 | pmid=32563380 | doi=10.1016/S0140-6736(20)30852-7 | pmc=7385662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32563380 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref><ref name="pmid12724485">{{cite journal| author=Kosten TR, O'Connor PG| title=Management of drug and alcohol withdrawal. | journal=N Engl J Med | year= 2003 | volume= 348 | issue= 18 | pages= 1786-95 | pmid=12724485 | doi=10.1056/NEJMra020617 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12724485 }} </ref><ref name="pmid18286804">{{cite journal| author=Kleber HD| title=Pharmacologic treatments for opioid dependence: detoxification and maintenance options. | journal=Dialogues Clin Neurosci | year= 2007 | volume= 9 | issue= 4 | pages= 455-70 | pmid=18286804 | doi= | pmc=3202507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18286804 }} </ref><ref name="pmid20407977">{{cite journal| author=Kreek MJ, Borg L, Ducat E, Ray B| title=Pharmacotherapy in the treatment of addiction: methadone. | journal=J Addict Dis | year= 2010 | volume= 29 | issue= 2 | pages= 200-16 | pmid=20407977 | doi=10.1080/10550881003684798 | pmc=2885886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20407977 }} </ref>
{| class="wikitable"
|+
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Half-lives of Opioids}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Onset of Withdrawal Symtoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|'''Short half-lives'''
*eg, [[heroin]] at 3–5 h
|Within 12 h of last use
|eg, [[heroin]] withdrawal lasts 4–5 days
|-
|'''Long half-lives'''
*eg, [[methadone]] at up to 96 h
|1–3 days after last use
|
*[[Methadone]] withdrawal lasts 7–14 days
*Some last for several weeks
|}

==Pathophysiology==
Chronic [[opioid]] use leads to changes in different organs and these may be the underlying pathophysiology of [[opioid]] withdrawal symptoms, such as: (((21 va asl.)))

* [[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
** Mu opioid receptors:
*** [[Diarrhea]], [[nausea and vomiting]]
* [[Brain]]:
** [[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
** <blockquote>Opioid craving, compulsive use, and [[depression]] Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]): [[Insomnia]] Different [[brain]] pathways (the [[Locus ceruleus|locus coeruleus (LC)]] in the [[Brain stem|brainstem]] and its projections including those to the [[reticular activating system]]): [[Physical dependence]] symptoms </blockquote>

=== Locus coeruleus (LC) ===

L[[Locus ceruleus|ocus coeruleus (LC)]]: (((((21))))

* Has [[Norepinephrine|norepinephrine (NE)]] neurons
* Input to several areas of the brain ([[prefrontal cortex]], [[hippocampus]], and [[amygdala]])
* Regulates [[attention]], vigilance, and [[autonomic nervous system]]

'''Acute opioid effects:'''

* [[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
* Due to binding of an [[opioid]] to m-opioid [[receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] which causes:

** Inhibition of the [[enzymes]] in the [[cAMP]] pathway
** Decreased firing rate of [[Locus ceruleus|LC]] neurons
** Decreased [[Norepinephrine|NE]] release

'''Chronic opioid use:'''

[[Opioid tolerance]] occurs with the adaption of [[Locus ceruleus|LC]] neurons to [[opioid]] inhibition by increasing [[enzyme]] activity which leads to:

* [[Upregulation]] of the [[cAMP]] pathway and production of normal [[cAMP]] levels:
** Return to normal levels of [[Locus ceruleus|LC]] firing rate and [[Norepinephrine|NE]] release

'''Abrupt discontinuation of opioids after opioid tolerance:'''

Sudden discontinuation of [[Opioid|opioids]] in chronic [[opioid]] users that have [[opioid tolerance]] causes the following until re-adaptation to the absence of [[Opioid|opioids]] occurs in [[Locus ceruleus|LC]] neurons: 9,22

* Hyperactivation of [[Locus ceruleus|LC]]
* Increased production of [[cAMP]]
* Excessive release of [[Norepinephrine|NE]]

[[Noradrenergic]] hyperactivity is the main cause of acute [[opioid]] withdrawal symptoms.

==Causes==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]].<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Differentiating opioid withdrawal from other diseases and conditions==
[[Opioid]] withdrawal must be differentiated from:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Benzodiazepines|Sedative-hypnotic withdrawal]]
*[[Hallucinogen]] intoxication
*[[Stimulant]] intoxication
*[[Opioid]]-induced [[Clinical depression|depressive disorder]]

{| class="wikitable"
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Disease}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Prominent clinical features}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Investigations}}
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:

*[[Palpitations]]
*[[Insomnia]]
*[[Anxiety]]
*[[Weight loss]]
*Heat intolerance
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
|
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Essential hypertension}}
|Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below:

*[[Headache]]
*[[Blurry vision]]
*[[Dyspnea]]
*[[Epistaxis]]
*[[Tinnitus]]
*[[Fatigue]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Electrolyte|Serum electrolytes]], especially [[potassium]]
*[[Calcium|Serum calcium]]
*[[Lipid profile]]: [[Total cholesterol]], [[LDL]], [[HDL]], [[triglycerides]]
*[[Creatinine]] or estimated [[GFR]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of [[generalized anxiety disorder]]:

#The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#The anxiety or the physical manifestations must affect the social and the daily life of the patient
#Exclusion of another medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
|<nowiki>-</nowiki>
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
|The [[perimenopausal]] symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of [[estrogens]], [[progestin]], and [[testosterone]]. Some of these symptoms such as [[formication]] etc may be associated with the hormone [[withdrawal]] process.

*Vasomotor instability in the form of [[hot flush]]es, including [[sleep hyperhidrosis|night sweats]] and [[Sleep disorder|sleep disturbances]]
*Urogenital atrophy causing [[Itch|itching]], dryness, [[bleeding]], watery discharge, [[Polyuria|urinary frequency]], [[urinary urgency]] and [[urinary incontinence]]
*Skeletal symptoms in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia|artharlgia]], [[myalgia|myalgia]] and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*Sexual disorders: [[Libido|decreased libido]], [[Vaginal lubrication|vaginal dryness]], problems reaching orgasm and [[dyspareunia]]
|
*[[Human chorionic gonadotropin|B-HCG]] should always be done first to rule out [[pregnancy]] especially in women under the age of 45 years
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Opioid withdrawal disorder}}
|According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:

#Cessation of (or reduction in) [[Opioid use disorders|opioid use]] that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an [[opioid antagonist]] after a period of [[Opioid use disorders|opioid use]].
#Development of three or more of the following criteria minutes to days after cessation of drug use: [[Dysphoria|dysphoric mood]], [[nausea]] or [[vomiting]], [[muscle aches]], [[Lacrimation]] or [[rhinorrhea]], [[pupillary dilation]], [[piloerection]], or [[sweating]], [[diarrhea]], [[yawning]], [[fever]], and [[insomnia]].
#The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
#The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
|
*Urine drug screen to rule out any other associated drug abuse
*Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
|The hallmark symptoms of a [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, symptoms usually subside in less than one hour and they may include:

*[[Palpitations]] especially in epinephrine producing tumors.
*[[Anxiety]] often resembling that of a [[panic attack]]
*[[Sweating]]
*[[Headaches]] occur in 90 % of patients.
*Paroxysmal attacks of [[hypertension]] but some patients have normal blood pressure.
*It may be asymptomatic and discovered by incidence screening especially [[MEN, type 2|MEN]] patients.

''Please note that not all patients with pheochromocytoma experience all classical symptoms''.
|Diagnostic lab findings associated with pheochromocytoma include:

*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated urinary [[vanillyl mandelic acid]]
|}

==Epidemiology and Demographics==
===Prevalence===
The [[prevalence]] of [[opioid]] withdrawal is 6,000 per 100,000 (60%) of the population that have used [[heroin]] one or more time in the prior 12 months.<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

==Risk Factors==
[[Opioid]] withdrawal may be caused by discontinuation of repeated use of an [[opioid]] in any setting such as:<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>

*[[Medical therapy]] of [[pain]]
*[[Opioid]] agonist therapy for [[opioid use disorder]]
*[[Recreational]] use
*Self-treating the symptoms of [[mental disorders]]

==Screening==

==Natural History, Complications and Prognosis==
Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days. The user, upon returning to the environment where they usually used opiates, can experience environmentally implied physical withdrawal symptoms well-after regaining physical homeostasis - or the termination of the physical withdrawal phase by synthesis of endogenous opioids (endorphins) and upregulation of [[opioid receptors]] to the effects of normal levels of endogenous opioids. These implied symptoms are often just as distressing and painful as the initial withdrawal phase.

Detoxification is best conducted in an in patient facility that provides a controlled environment. Patients who are isolated and exposed solely to care givers and other patients in this environment have a better rate of staying clean then those who detox out-patient.

==Diagnosis==
===Diagnostic Criteria===
====DSM-V Diagnostic Criteria for Opioid Withdrawal<ref name="DSMV">{{cite book | title = Diagnostic and statistical manual of mental disorders : DSM-5 | publisher = American Psychiatric Association | location = Washington, D.C | year = 2013 | isbn = 0890425558 }}</ref>====
{{cquote|
*A. Presence of either of the following;
:*1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer).
:*2. Administration of an opioid antagonist after a period of opioid use.

'''''AND'''''

*B. Three (or more) of the following developing within minutes to several days after Criterion A:
:*1. Dysphoric mood.
:*2. Nausea or vomiting.
:*3. Muscle aches.
:*4. [[Lacrimation]] or [[rhinorrhea]].
:*5. Pupillary dilation, piloerection, or sweating.
:*6. [[Diarrhea]].
:*7. [[Yawning]].
:*8. Fever.
:*9.[[Insomnia]].

'''''AND'''''

*C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

'''''AND'''''

*D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.
}}

===History and Symptoms===
The most common [[symptoms]] of [[opioid]] withdrawal include :<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref>

*[[Anxiety]]
*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Insomnia]]
*[[Hot flashes]]
*[[Chills]]
*[[Sweating]]
*[[Pupillary dilatation]]
*[[Heart]] pounding
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*Gooseflesh
*[[Nausea, vomiting]]
*[[Abdominal]] cramps
*[[Diarrhea]]
*[[Aches]], pain
*Muscle [[spasms]], twitching
*[[Tremor]]

===Physical Examination===
Common [[physical examination]] findings of [[opioid]] withdrawal include:<ref name="pmid12924748">{{cite journal| author=Wesson DR, Ling W| title=The Clinical Opiate Withdrawal Scale (COWS). | journal=J Psychoactive Drugs | year= 2003 | volume= 35 | issue= 2 | pages= 253-9 | pmid=12924748 | doi=10.1080/02791072.2003.10400007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12924748 }} </ref><ref name="pmid27124502">{{cite journal| author=Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T| title=Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification. | journal=Addict Behav | year= 2016 | volume= 60 | issue= | pages= 109-16 | pmid=27124502 | doi=10.1016/j.addbeh.2016.03.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27124502 }} </ref><ref name="pmid30701615">{{cite journal| author=Kosten TR, Baxter LE| title=Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. | journal=Am J Addict | year= 2019 | volume= 28 | issue= 2 | pages= 55-62 | pmid=30701615 | doi=10.1111/ajad.12862 | pmc=6590307 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30701615 }} </ref>

*[[Anxiety]]
*[[Restlessness]]
*[[Irritability]]
*[[Hypertension]]
*[[Tachycardia]]
*[[Mydriasis]]
*[[Piloerection]] (such as goose bumps)
*[[Lacrimation]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Diarrhea]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*[[Tremor]]

===Laboratory Findings===
Patients with [[opioid]] use disorder (particularly [[intravenous]] [[heroin]] dependence) may be tested for [[complications]]:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Laboratory]] tests
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]

===X-ray===
There are no [[X-rays|x-ray]] findings associated with [[opioid]] withdrawal.

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with [[opioid]] withdrawal.

===CT Scan===
There are no [[Computed tomography|CT scan]] findings associated with [[opioid]] withdrawal.

===MRI===
There are no [[Magnetic resonance imaging|MRI]] findings associated with [[opioid]] withdrawal.

===Other Imaging Findings===
There are no other [[imaging]] findings associated with [[opioid]] withdrawal.

===Other Diagnostic Studies===
here are no other [[diagnostic]] studies associated with [[opioid]] withdrawal.

==Treatment==
===Medical Therapy===
[[Medication|Medications]] used in [[opioid]] withdrawal include:<ref name="pmid22514851">{{cite journal| author=Center for Substance Abuse Treatment| title=Detoxification and Substance Abuse Treatment | journal=SAMHSA/CSAT Treatment Improvement Protocols | year= 2006 | volume= | issue= | pages= | pmid=22514851 | doi= | pmc= | url= }} </ref>

*[[Methadone]]
**[[Methadone]] is a [[long-acting agonist]] at the [[μ-opioid receptor]]
**[[Dose]]:
***The initial [[dose]] is determined by estimating the amount of [[opioid]] use and the patient's response.
***[[Methadone]] may be administered once daily, and tapered over 3 to 5 days (in 5 to 10mg daily reductions)
**[[Methadone]] is the most commonly used [[medication]], but patients require adjunctive [[drugs]] for [[Nausea and vomiting|nausea, vomiting]], [[diarrhea]], and stomach [[Cramp|cramps]]
*[[Clonidine]]
**[[Clonidine]] is an α-[[adrenergic agonist]]
**Administered 0.1mg [[Orally ingested|orally]]
**A [[dose]] of 0.2mg might be used initially in patients:
***With severe signs of [[opioid]] withdrawal
***Weighing more than 200 pounds
**Treatment with [[clonidine]] requires adjunctive medicines for [[insomnia]], [[myalgia]], [[bone pain]], and [[headache]].
*[[Buprenorphine]]
**[[Buprenorphine]] is a partial μ-[[opioid agonist]]

===Surgery===
[[Surgery|Surgical]] intervention is not recommended for the management of [[opioid]] withdrawal.

===Primary Prevention===
===Primary Prevention===

==References==
{{Reflist|2}}

{{Mental and behavioural disorders}}
[[Category:Abuse]]
[[Category:Substance abuse]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
{{WikiDoc Sources}}

Opioid withdrawal

2020-12-16T13:07:55Z

ShakibaHassanzadeh:

Opioid withdrawal

2020-12-16T13:06:56Z

ShakibaHassanzadeh: /* Surgery */

Opioid withdrawal

2020-12-16T12:52:00Z

ShakibaHassanzadeh: /* Surgery */

Opioid withdrawal

2020-12-16T12:46:15Z

ShakibaHassanzadeh: /* Medical Therapy */

Opioid withdrawal

2020-12-16T12:43:27Z

ShakibaHassanzadeh: /* Treatment */

Opioid withdrawal

2020-12-16T12:43:05Z

ShakibaHassanzadeh: /* Medical Therapy */

Opioid withdrawal

2020-12-16T12:05:00Z

ShakibaHassanzadeh: /* Classification */

Opioid withdrawal

2020-12-16T12:00:26Z

ShakibaHassanzadeh: /* Classification */

Opioid withdrawal

2020-11-25T13:34:59Z

ShakibaHassanzadeh:

Opioid withdrawal

2020-11-25T13:02:33Z

ShakibaHassanzadeh: /* Diagnosis */

Opioid withdrawal

2020-11-25T12:38:43Z

ShakibaHassanzadeh: /* Epidemiology and Demographics */

Opioid withdrawal

2020-11-25T12:35:42Z

ShakibaHassanzadeh: /* Causes */

Opioid withdrawal

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ShakibaHassanzadeh: /* Causes */

Opioid withdrawal

2020-11-25T12:24:56Z

ShakibaHassanzadeh:

User:ShakibaHassanzadeh

2020-11-17T16:20:42Z

ShakibaHassanzadeh: /* Pages Authored/Co-authored */

==Shakiba Hassanzadeh M.D.==

== Pages Authored/Co-authored ==
'''Primary Care Project:'''

[[Alcohol Withdrawal]]

[[Seizure]]

[[Endometritis]]

'''COVID-19 Project:'''

[[COVID-19-associated cytokine storm]]

[[COVID-19-associated thrombocytopenia]]

[[COVID-19-associated anemia]]

[[COVID-19-associated hematologic findings]]

'''Other:'''

[[Shaken baby syndrome|Shaken Baby Syndrome]]

[[Biliary dyskinesia|Biliary Dyskinesia]]

[[Renal agenesis|Renal Agenesis]]

[[Milk-alkali syndrome|Milk-alkali Syndrome]]

[[Analgesic nephropathy|Analgesic Nephropathy]]

[[HIV associated nephropathy|HIV-associated Nephropathy]]

[[Asperger syndrome|Asperger Syndrome]]

[[Transesophageal echocardiography (TEE)]]