Opioid withdrawal: Difference between revisions

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==Overview==
==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]].
[[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|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==
==Historical Perspective==
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{| class="wikitable"
{| 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|Half-life 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|Onset of Withdrawal Symptoms}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
! colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Duration of the syndrome}}
|-
|-
|'''Short half-lives'''
|'''Short half-life'''
*eg, [[heroin]] at 3–5 h
*[[Heroin]] at 3–5 h
|Within 12 h of last use
|
|eg, [[heroin]] withdrawal lasts 4–5 days
*Within 12 h of last use
|
*[[Heroin]] withdrawal lasts 4–5 days
|-
|-
|'''Long half-lives'''
|'''Long half-life'''
*eg, [[methadone]] at up to 96 h
*[[Methadone]] up to 96 h
|1–3 days after last use
|
*1–3 days after last use
|
|
*[[Methadone]] withdrawal lasts 7–14 days
*[[Methadone]] withdrawal lasts 7–14 days
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==Pathophysiology==
==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>
[[Chronic (medical)|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]]:
*[[Gastrointestinal tract|Gastrointestinal (GI) tract]]:
**Mu opioid receptors:
**[[Mu opioid receptor|Mu opioid receptors]]:
***[[Diarrhea]], [[nausea and vomiting]]
***[[Diarrhea]], [[nausea and vomiting]]
*[[Brain]]:
*[[Brain]]:
**[[Mesolimbic pathway|Mesolimbic]] reward circuits (the [[Ventral tegmentum|ventral tegmental area]] and its projections to [[nucleus accumbens]], [[prefrontal cortex]], and [[amygdala]]):
**[[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]]
***[[Opioid]] craving, compulsive use and [[depression]]
**Ascending [[reticular activating system]] (in the [[Brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
**Ascending [[reticular activating system]] (in the [[brain stem|brainstem]], [[thalamus]], and [[hypothalamus]]):
***[[Insomnia]]
***[[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]]):
**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
***[[Physical dependence]] symptoms


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


'''Acute opioid effects:'''
'''Acute opioid effects:'''


*[[Drowsiness]], [[hypotension]], reduced [[respiration]] and [[muscle tone]]
*[[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:
*Binding of an [[opioid]] to [[Mu Opioid receptor|mu-opioid receptors]] on the [[Neuron|neurons]] in [[Locus ceruleus|LC]] causes:
**Inhibition of the [[enzymes]] in the [[cAMP]] pathway
**[[Inhibition]] of the [[enzymes]] in the [[cAMP]] pathway
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased firing rate of [[Locus ceruleus|LC]] neurons
**Decreased [[Norepinephrine|NE]] release
**Decreased [[Norepinephrine|NE]] release
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*Hyperactivation of [[Locus ceruleus|LC]]
*Hyperactivation of [[Locus ceruleus|LC]]
*Increased production of [[cAMP]]
*Increased production of [[cAMP]]
*Excessive release of [[Norepinephrine|NE]]
*Excessive release of [[Norepinephrine|NE]]


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


==Causes==
==Causes==
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|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Hyperthyroidism}}
|The main symptoms include:
|The main [[Symptom|symptoms]] include:


*[[Palpitations]]
*[[Palpitations]]
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*Heat intolerance
*Heat intolerance
*[[Diarrhea]]
*[[Diarrhea]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmus]] or [[goiter]]
*Depending on the underlying diagnosis, the patient might have [[exophthalmos]] or [[goiter]]
|
|
*The patient usually has elevated [[T3]] and [[T4]]
*The patient usually has elevated [[T3]] and [[T4]]
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSH]] might be increased or decreased depending on the underlying cause
*[[TSI|Thyroid stimulating antibodies (TSI)]] might be increased in cases of [[Graves’ disease]]
*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}}
| 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:
|Most patients with hypertension are [[asymptomatic]] at the time of [[diagnosis]]. Common symptoms are listed below:


*[[Headache]]
*[[Headache]]
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*[[Fatigue]]
*[[Fatigue]]
*[[Drowsiness]]
*[[Drowsiness]]
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension''':'''
|JNC 7 recommends the following routine laboratory tests before initiation of therapy for [[hypertension]]''':'''
*[[ECG|12-Lead electrocardiogram (ECG)]]
*A 12-Lead [[electrocardiogram]] ([[The electrocardiogram|ECG]])
*[[Urinalysis]], including urinary albumin excretion or albumin/creatinine ratio
*[[Urinalysis]], including urinary [[albumin]] excretion or [[albumin]]/[[creatinine]] ratio
*[[Blood glucose]]
*[[Blood glucose]]
*[[Hematocrit|Blood hematocrit]]
*[[Hematocrit|Blood hematocrit]]
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|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Generalized anxiety disorder}}
| 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]]:
|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
#The presence of a sense of apprehension or fear toward certain activities for most of the days for at least 6 months
#Difficulty to control the apprehension
#Difficulty to control the apprehension
#Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
#Associated restlessness, [[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
#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 medical condition or the effect of another administered substance
#Exclusion of another mental disorder causing the symptoms
#Exclusion of another [[mental disorder]] causing the symptoms
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Menopause}}
| 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.
|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]]
*[[Vasomotor]] instability in the form of [[hot flash]]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]]
*[[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]]
*[[Skeletal]] [[Symptom|symptoms]] in the form of [[osteoporosis]] (gradually developing over time), [[arthralgia]], [[myalgia|myalgia]], and [[back pain]]
*Psychological manifestations such as [[Mood disorder|mood disturbance]], [[irritability]], [[Fatigue (medical)|fatigue]], [[memory loss]] and [[Depression (mood)|depression]]
*[[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]]
*[[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
*[[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
*[[FSH]] can be measured but it can be falsely normal or low
*[[TSH]], [[T3]] and [[T4]] to rule out thyroid abnormalities
*[[TSH]], [[T3]], and [[T4]] to rule out thyroid abnormalities
*[[Prolactin]] can be measured to rule out [[prolactinoma]] as a cause of [[menopause]]
*[[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}}
| 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:
|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]].
#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]].
#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 [[Symptom|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.
#The signs or [[symptoms]] mentioned above must not be attributed to other medical or [[Mental disorder|mental disorders]].
|
|
*Urine drug screen to rule out any other associated drug abuse
*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
*Routine blood work such as [[Electrolyte|electrolytes]] and [[hemoglobin]] to rule out any associated disease explaining the [[Symptom|symptoms]]
|-
|-
| colspan="1" rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Pheochromocytoma}}
| 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:
|The hallmark [[Symptom|symptoms]] of [[pheochromocytoma]] are those of [[sympathetic nervous system]] hyperactivity, [[Symptom|symptoms]] usually subside in less than one hour and they may include:


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


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


*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
*Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
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*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>
*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>
*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>
*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==
==Risk Factors==
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{{cquote|
{{cquote|
*A. Presence of either of the following;
*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).
:*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.
:*2. Administration of an [[opioid antagonist]] after a period of [[opioid]] use.


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*[[Rhinorrhea]]
*[[Rhinorrhea]]
*[[Yawning]]
*[[Yawning]]
*[[Nausea, vomiting]]
*[[Nausea]], [[vomiting]]
*[[Diarrhea]]
*[[Diarrhea]]
*[[Sweating]]
*[[Sweating]]
*Muscle [[spasms]], twitching
*Muscle [[spasms]], [[twitching]]
*[[Tremor]]
*[[Tremor]]


Line 293: Line 296:
*[[Tuberculosis]]
*[[Tuberculosis]]
*[[HIV AIDS|HIV/AIDS]]
*[[HIV AIDS|HIV/AIDS]]
*Viral [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*[[Viral]] [[hepatitis]] (especially [[Hepatitis B virus|B]] and [[Hepatitis C|C]])
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*Other [[Sexually transmitted disease|sexually transmitted diseases]]
*[[Opportunistic infections]]
*[[Opportunistic infections]]
Line 351: Line 354:
*Refraining from sudden and abrupt discontinuation of [[opioid]] use in individuals with [[opioid]] dependence.
*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]] 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>
*[[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.
*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>
*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>
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==References==
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[[Category: Substance abuse]]
[[Category:Psychiatry]]
[[Category:Psychiatry]]
[[Category:Toxicology]]
[[Category:Toxicology]]
[[Category:Substance-related disorders]]
[[Category:Substance-related disorders]]
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{{WikiDoc Sources}}
[[Category: Up-To-Date]]

Latest revision as of 20:40, 14 January 2021



Resident
Survival
Guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2], Kiran Singh, M.D. [3]

WikiDoc Resources for Opioid withdrawal

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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, depression, anxiety, irritability, leg cramps, abdominal cramps, nausea, vomiting, diarrhea, insomnia, pain, tremor, rhinorrhea, sweating, and cravings for the drug itself. Depending on the opioid's half-life, the 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 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.[1]
  • 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.[1]
  • 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.[1]

Classification

The onset and duration of opioid withdrawal depends on the half-life of the consumed opioid:[2][1][3][4][5]

Half-life of Opioids Onset of Withdrawal Symptoms Duration of the syndrome
Short half-life
  • Within 12 h of last use
  • Heroin withdrawal lasts 4–5 days
Long half-life
  • 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:[6][1]

Locus coeruleus (LC)

Locus ceruleus(LC):[6]

Acute opioid effects:

Chronic opioid use:

Opioid tolerance occurs with the adaption of 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 LC firing rate and NE release

Abrupt discontinuation of opioids after opioid tolerance:

Sudden discontinuation of opioids in chronic opioid users that have opioid tolerance causes the following until re-adaptation to the absence of opioids occurs in LC neurons:[7][8] 

  • Hyperactivation of LC
  • Increased production of cAMP
  • Excessive release of NE

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

Causes

Opioid withdrawal symptoms may occur with:[9]

Differentiating opioid withdrawal from other diseases and conditions

Opioid withdrawal must be differentiated from:[10]

Disease Prominent clinical features Investigations
Hyperthyroidism The main symptoms include:
  • The patient usually has elevated T3 and T4
  • TSH might be increased or decreased depending on the underlying cause
  • Thyroid-stimulating antibodies (TSI) might be increased in cases of Graves’ disease
Essential hypertension Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below: JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension:
Generalized anxiety disorder According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder:
  1. The presence of a sense of apprehension or fear toward certain activities for most of the days for at least 6 months
  2. Difficulty to control the apprehension
  3. Associated restlessness, fatigue, irritability, difficult concentration, muscle tension or, sleep disturbance (only one of these manifestations)
  4. The anxiety or the physical manifestations must affect the social and the daily life of the patient
  5. Exclusion of another medical condition or the effect of another administered substance
  6. Exclusion of another mental disorder causing the symptoms
-
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.
  • 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
Opioid withdrawal disorder According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:
  1. Cessation of (or reduction in) 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.
  2. Development of three or more of the following criteria minutes to days after cessation of drug use: dysphoric mood, nausea or vomiting, muscle aches, Lacrimation or rhinorrhea, pupillary dilation, piloerection, or sweating, diarrhea, yawning, fever, and insomnia.
  3. The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
  4. 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
Pheochromocytoma The hallmark symptoms of pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include:

Please note that not all patients with pheochromocytoma experience all of the classical symptoms.

Diagnostic lab findings associated with pheochromocytoma include:

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.[10]
  • In the USA, the amount of opioids prescribed has increased from 43.8 million prescriptions in 2000 to 89.2 million in 2010.[11]
  • About 4% of adults in the USA regularly use opioids for pain.[12]

Risk Factors

Opioid withdrawal may be caused by discontinuation of repeated use of an opioid in any setting such as:[10]

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

DSM-V Diagnostic Criteria for Opioid Withdrawal[10]

  • 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:

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

History and Symptoms

The most common symptoms of opioid withdrawal include :[16][17]

Physical Examination

Common physical examination findings of opioid withdrawal include:[16][17][1]

Laboratory Findings

Patients with opioid use disorder (particularly intravenous heroin dependence) may be tested for complications:[18]

X-ray

There are no 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 CT scan findings associated with opioid withdrawal.

MRI

There are no 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:[19]

  • Short Opioid Withdrawal Scale (SOWS)[20][21]
  • Objective Opiate Withdrawal Scale (OOWS)[21]
  • Opiate Craving Scale (OCS)
  • Opiate Withdrawal Scale (OWS)

Treatment

Medical Therapy

Medications used in opioid withdrawal include:[18]

Surgery

Surgical intervention is not recommended for the management of opioid withdrawal.

Prevention

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Kosten TR, Baxter LE (2019). "Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment". Am J Addict. 28 (2): 55–62. doi:10.1111/ajad.12862. PMC 6590307 Check |pmc= value (help). PMID 30701615.
  2. Srivastava AB, Mariani JJ, Levin FR (2020). "New directions in the treatment of opioid withdrawal". Lancet. 395 (10241): 1938–1948. doi:10.1016/S0140-6736(20)30852-7. PMC 7385662 Check |pmc= value (help). PMID 32563380 Check |pmid= value (help).
  3. Kosten TR, O'Connor PG (2003). "Management of drug and alcohol withdrawal". N Engl J Med. 348 (18): 1786–95. doi:10.1056/NEJMra020617. PMID 12724485.
  4. Kleber HD (2007). "Pharmacologic treatments for opioid dependence: detoxification and maintenance options". Dialogues Clin Neurosci. 9 (4): 455–70. PMC 3202507. PMID 18286804.
  5. Kreek MJ, Borg L, Ducat E, Ray B (2010). "Pharmacotherapy in the treatment of addiction: methadone". J Addict Dis. 29 (2): 200–16. doi:10.1080/10550881003684798. PMC 2885886. PMID 20407977.
  6. 6.0 6.1 Mazei-Robison MS, Nestler EJ (2012). "Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons". Cold Spring Harb Perspect Med. 2 (7): a012070. doi:10.1101/cshperspect.a012070. PMC 3385942. PMID 22762025.
  7. Kosten TR, George TP (2002). "The neurobiology of opioid dependence: implications for treatment". Sci Pract Perspect. 1 (1): 13–20. doi:10.1151/spp021113. PMC 2851054. PMID 18567959.
  8. Cao JL, Vialou VF, Lobo MK, Robison AJ, Neve RL, Cooper DC; et al. (2010). "Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons". Proc Natl Acad Sci U S A. 107 (39): 17011–6. doi:10.1073/pnas.1010077107. PMC 2947876. PMID 20837544.
  9. Diagnostic and statistical manual of mental disorders : DSM-5. Arlington, VA Washington, D.C: American Psychiatric Association,American Psychiatric Association. 2013. ISBN 0-89042-555-8. OCLC 830807378.
  10. 10.0 10.1 10.2 10.3 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
  11. Sites BD, Beach ML, Davis MA (2014). "Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users". Reg Anesth Pain Med. 39 (1): 6–12. doi:10.1097/AAP.0000000000000022. PMC 3955827. PMID 24310049.
  12. Volkow ND, McLellan AT (2016). "Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies". N Engl J Med. 374 (13): 1253–63. doi:10.1056/NEJMra1507771. PMID 27028915.
  13. Mattick RP, Breen C, Kimber J, Davoli M (2014). "Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence". Cochrane Database Syst Rev (2): CD002207. doi:10.1002/14651858.CD002207.pub4. PMID 24500948.
  14. Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE; et al. (2018). "Extended-release injectable naltrexone for opioid use disorder: a systematic review". Addiction. 113 (7): 1188–1209. doi:10.1111/add.14180. PMC 5993595. PMID 29396985.
  15. 15.0 15.1 Burma NE, Kwok CH, Trang T (2017). "Therapies and mechanisms of opioid withdrawal". Pain Manag. 7 (6): 455–459. doi:10.2217/pmt-2017-0028. PMID 29125396.
  16. 16.0 16.1 Wesson DR, Ling W (2003). "The Clinical Opiate Withdrawal Scale (COWS)". J Psychoactive Drugs. 35 (2): 253–9. doi:10.1080/02791072.2003.10400007. PMID 12924748.
  17. 17.0 17.1 Vernon MK, Reinders S, Mannix S, Gullo K, Gorodetzky CW, Clinch T (2016). "Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification". Addict Behav. 60: 109–16. doi:10.1016/j.addbeh.2016.03.028. PMID 27124502.
  18. 18.0 18.1 Center for Substance Abuse Treatment (2006). "Detoxification and Substance Abuse Treatment". SAMHSA/CSAT Treatment Improvement Protocols. PMID 22514851.
  19. 19.0 19.1 Doughty B, Morgenson D, Brooks T (2019). "Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal". Ann Pharmacother. 53 (7): 746–753. doi:10.1177/1060028019828954. PMID 30724094.
  20. Gossop M (1990). "The development of a Short Opiate Withdrawal Scale (SOWS)". Addict Behav. 15 (5): 487–90. doi:10.1016/0306-4603(90)90036-w. PMID 2248123.
  21. 21.0 21.1 Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD (1987). "Two new rating scales for opiate withdrawal". Am J Drug Alcohol Abuse. 13 (3): 293–308. doi:10.3109/00952998709001515. PMID 3687892.

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