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| {{Infobox_Disease | | | {{Tricyclic antidepressant overdose}} |
| Name = Tricyclic antidepressant overdose |
| | '''For patient information, click [[Tricyclic antidepressant overdose (patient information)|here]]''' |
| Caption = Chemical structure of the tricyclic antidepressant [[amitriptyline]] |
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| ICD10 = {{ICD10|T|43|0|t|36}} |
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| ICD9 = {{ICD9|969.0}} |
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| ==Overview==
| | {{CMG}}; {{AE}} {{RT}} |
| Tricyclic antidepressant overdose is caused by excessive use or overdose of a [[tricyclic antidepressant]] drug. It is a significant cause of fatal drug [[poison]]ing. The severe [[morbidity]] and mortality associated with these drugs is well documented due to their [[circulatory system|cardiovascular]] and [[neurology|neurological]] toxicity. Additionally, it is a serious problem in the pediatric population due to their potential toxicity<ref name="JEmergMed2005-Rosenbaum">{{cite journal | author = Rosenbaum T, Kou M | title = Are one or two dangerous? Tricyclic antidepressant exposure in toddlers | journal = J Emerg Med | volume = 28 | issue = 2 | pages = 169–74 | year = 2005 | pmid = 15707813 | doi = 10.1016/j.jemermed.2004.08.018}}</ref> and the availability of these in the home when prescribed for bed wetting and depression.
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| ==Epidemiology and Demographics== | | ==[[Tricyclic antidepressant overdose overview|Overview]]== |
| | ==[[Tricyclic antidepressant overdose historical perspective|Historical Perspective]]== |
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| Studies in the 1990s in [[Australia]] and the [[United Kingdom]] showed that between 8 and 12% of drug overdoses were following TCA ingestion. TCAs may be involved in up to 33% of all fatal poisonings, second only to [[analgesics]].<ref name="humexptoxicol1996-thomas">{{cite journal | doi = 10.1177/096032719601500602 | author = Thomas S, Bevan L, Bhattacharyya S, Bramble M, Chew K, Connolly J, Dorani B, Han K, Horner J, Rodgers A, Sen B, Tesfayohannes B, Wynne H, Bateman D | title = Presentation of poisoned patients to accident and emergency departments in the north of England | journal = Hum Exp Toxicol | volume = 15 | issue = 6 | pages = 466–70 | year = 1996 | pmid = 8793528}}</ref><ref name="MedJAust1995-Buckley">{{cite journal | author = Buckley N, Whyte I, Dawson A, McManus P, Ferguson N | title = Self-poisoning in Newcastle, 1987-1992 | journal = Med J Aust | volume = 162 | issue = 4 | pages = 190–3 | year = 1995 | pmid = 7877540}}</ref> Another study reported 95% of deaths from antidepressants in England and Wales between 1993 and 1997 were associated with tricyclic antidepressants, particularly [[dothiepin]] and [[amitriptyline]]. It was determined there were 5.3 deaths per 100,000 prescriptions.<ref>{{cite journal |author=Shah R, Uren Z, Baker A, Majeed A |title=Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database |journal=Psychol Med |volume=31 |issue=7 |pages=1203–10 |year=2001 |month=October |pmid=11681546}}</ref>
| | ==[[Tricyclic antidepressant overdose pathophysiology|Pathophysiology]]== |
| [[Sodium channel blockers]] such as [[Dilantin]] should not be used in the treatment of TCA overdose as the [[Sodium|Na+]] blockade will increase the [[QT interval|QTI]].
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| ==Pathophysiology== | | ==[[Tricyclic antidepressant overdose causes|Causes]]== |
| [[File:TCAECGOD.PNG|thumb|QRS widening seen in a person who has overdosed on TCAs]]
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| Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have [[anticholinergic]] effects, cause excessive blockade of [[norepinephrine]] reuptake at the preganglionic [[synapse]], direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having [[quinidine]] like effects on the [[myocardium]].<ref name="EmergMedJ2001-Kerr">{{cite journal | author = Kerr G, McGuffie A, Wilkie S | title = Tricyclic antidepressant overdose: a review | journal = Emerg Med J | volume = 18 | issue = 4 | pages = 236–41 | year = 2001 | pmid = 11435353 | doi = 10.1136/emj.18.4.236 | pmc = 1725608}}</ref>
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| ===Toxicity=== | | ==[[Tricyclic antidepressant overdose differential diagnosis|Differentiating Tricyclic Antidepressant Overdose from other Diseases]]== |
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| Tricyclics have a narrow [[therapeutic index]], ''i.e.'', the therapeutic [[Dose (biochemistry)|dose]] is close to the toxic dose.<ref name="Woolf-2007">{{cite journal |author=Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG |title=Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management |journal=Clin Toxicol (Phila) |volume=45 |issue=3 |pages=203–33 |year=2007 |pmid=17453872 |doi=10.1080/15563650701226192}}</ref> In the medical literature the lowest reported toxic dose is 6.7 mg per kg body weight. Although there are differences in toxicity with the drug class, ingestions of 10 to 20 mg per kilogram of body weight are a risk for moderate to severe poisoning, however, doses ranging from 1.5 to 5 mg/kg may even present a risk. Most [[poison control center]]s refer any case of TCA poisoning (especially in children) to a hospital for monitoring.<ref name="clintox2000-McFee">{{cite journal | author = McFee R, Mofenson H, Caraccio T | title = A nationwide survey of the management of unintentional-low dose tricyclic antidepressant ingestions involving asymptomatic children: implications for the development of an evidence-based clinical guideline |journal = J Toxicol Clin Toxicol | volume = 38 | issue = 1 | pages = 15–9 | year = 2000 | pmid = 10696919 | doi = 10.1081/CLT-100100910}}</ref> Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.<ref name="JClinPsychiatry1982-Preskorn">{{cite journal | author = Preskorn S, Irwin H | title = Toxicity of tricyclic antidepressants--kinetics, mechanism, intervention: a review | journal = J Clin Psychiatry | volume = 43 | issue = 4 | pages = 151–6 | year = 1982 | pmid = 7068546}}</ref> However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.<ref name="NEngJMed1985-Boehnert">{{cite journal | doi = 10.1056/NEJM198508223130804 | author = Boehnert M, Lovejoy F | title = Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants | journal = N Engl J Med | volume = 313 | issue = 8 | pages = 474–9 | year = 1985 | pmid = 4022081}}</ref>
| | ==[[Tricyclic antidepressant overdose epidemiology and demographics|Epidemiology and Demographics]]== |
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| | ==[[Tricyclic antidepressant overdose risk factors|Risk Factors]]== |
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| | ==[[Tricyclic antidepressant overdose natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==Diagnosis== | | ==Diagnosis== |
| ===Signs and symptoms===
| | [[Tricyclic antidepressant overdose history and symptoms|History and Symptoms]] | [[Tricyclic antidepressant overdose physical examination|Physical Examination]] | [[Tricyclic antidepressant overdose laboratory findings|Laboratory Findings]] | [[Tricyclic antidepressant overdose electrocardiogram|Electrocardiogram]] | [[Tricyclic antidepressant overdose CT|CT]] | [[Tricyclic antidepressant overdose MRI|MRI]] | [[Tricyclic antidepressant overdose other imaging findings|Other Imaging Findings]] | [[Tricyclic antidepressant overdose other diagnostic studies|Other Diagnostic Studies]] |
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| The peripheral [[autonomic nervous system]], [[central nervous system]] and the [[heart]] are the main systems that are affected following overdose.<ref name="EmergMedJ2001-Kerr"/> Initial or mild symptoms typically develop within 2 hours and include [[tachycardia]], [[drowsiness]], a dry mouth, [[nausea]] and [[vomiting]], urinary retention, confusion, agitation, and [[headache]].<ref name="Woolf-2007"/> More severe complications include [[hypotension]], cardiac rhythm disturbances, [[hallucinations]], and [[seizures]]. [[Electrocardiogram]] (ECG) abnormalities are frequent and a wide variety of [[Cardiac arrhythmia|cardiac dysrhythmias]] can occur, the most common being sinus tachycardia and intraventricular conduction delay resulting in prolongation of the [[QRS complex]] and the [[PR interval|PR]]/[[QT interval|QT intervals]].<ref name="toxicolrev2005-Thanacoody">{{cite journal | author = Thanacoody H, Thomas S | title = Tricyclic antidepressant poisoning : cardiovascular toxicity | journal = Toxicol Rev | volume = 24 | issue = 3 | pages = 205–14 | year = 2005 | pmid = 16390222 | doi = 10.2165/00139709-200524030-00013}}</ref> Seizures, cardiac dysrhythmias, and apnea are the most important life threatening complications.<ref name="Woolf-2007"/>
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| ==Treatment== | | ==Treatment== |
| | [[Tricyclic antidepressant overdose medical therapy|Medical Therapy]] | [[Tricyclic antidepressant overdose primary prevention|Primary Prevention]] | [[Tricyclic antidepressant overdose secondary prevention|Secondary Prevention]] | [[Tricyclic antidepressant overdose cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Tricyclic antidepressant overdose future or investigational therapies|Future or Investigational Therapies]] |
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| Initial treatment of an acute overdose includes gastric decontamination of the patient. This is achieved by administering [[activated charcoal]] lavage which [[Absorption (chemistry)|absorbs]] the drug in the [[gastrointestinal tract]] either orally or via a [[nasogastric tube]]. Activated charcoal is most useful if given within 1 to 2 hours of ingestion.<ref name="dart">{{cite book |last=Dart| first= RC |chapter= |title=Medical toxicology |publisher=Williams & Wilkins| location=Philadelphia |year=2004|pages=834–43| isbn=0-7817-2845-2}}</ref> Other decontamination methods such as [[gastric lavage|stomach pumps]], [[Syrup of ipecac|ipecac]] induced emesis, or [[whole bowel irrigation]] are not recommended in TCA poisoning.<ref name="EmergMedJ2003-Teece">{{cite journal | author = Teece S, Hogg K | title = Gastric lavage in tricyclic antidepressant overdose | journal = Emerg Med J | volume = 20 | issue = 1 | pages = 64 | year = 2003 | pmid = 12533375 | doi = 10.1136/emj.20.1.64 | pmc = 1726003}}</ref><ref name="toxicolrev2005-dargan">{{cite journal | author = Dargan P, Colbridge M, Jones A | title = The management of tricyclic antidepressant poisoning : the role of gut decontamination, extracorporeal procedures and fab antibody fragments | journal = Toxicol Rev | volume = 24 | issue = 3 | pages = 187–94 | year = 2005 | pmid = 16390220 | doi = 10.2165/00139709-200524030-00011}}</ref>
| | == Case Studies == |
| | | [[Tricyclic antidepressant overdose case study one|Case #1]] |
| Symptomatic patients are usually monitored in an [[intensive care unit]] for a minimum of 12 hours, with close attention paid to maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring.<ref name="EmergMedJ2001-Kerr"/> Supportive therapy is given if necessary, including respiratory assistance, maintenance of body temperature, and administration of [[intravenous sodium bicarbonate]] as an [[antidote]], which has been shown to be an effective treatment for resolving the [[metabolic acidosis]] and cardiovascular complications of TCA poisoning. If sodium bicarbonate therapy fails to improve cardiac symptoms, conventional antidysrhythmic drugs such as [[phenytoin]] and [[magnesium]] can be used to reverse any cardiac abnormalities. However, no benefit has been shown from [[lidocaine]] or other class 1a and 1c antiarrhythmic drugs; it appears they worsen the sodium channel blockade, slow conduction velocity, and depress contractility and should be avoided in TCA poisoning.<ref name="toxicolrev2005-bradberry">{{cite journal | author = Bradberry S, Thanacoody H, Watt B, Thomas S, Vale J | title = Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate | journal = Toxicol Rev | volume = 24 | issue = 3 | pages = 195–204 | year = 2005 | pmid = 16390221 | doi = 10.2165/00139709-200524030-00012}}</ref> Hypotension is initially treated with fluids along with bicarbonate to reverse [[metabolic acidosis]] (if present), if the patient remains hypotensive despite fluids then further measures such as the administration of [[epinephrine]], [[norepinephrine]], or [[dopamine]] can be used to increase blood pressure.<ref name="toxicolrev2005-bradberry"/> Another potentially severe symptom is seizures: Seizures often resolve without treatment but administration of a [[benzodiazepine]] or other anticonvulsive may be required for persistent muscular overactivity. There is no role for [[physostigmine]] in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures.<ref name="EmergMedJ2001-Kerr"/>
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| Tricyclic antidepressants are highly protein bound and have a large [[volume of distribution]]; therefore removal of these compounds from the blood with [[hemodialysis]], [[hemoperfusion]] or other techniques are unlikely to be of any significant benefit.<ref name="toxicolrev2005-dargan"/>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Toxicology]] | | [[Category:Toxicology]] |