View source for Medicine:Tricyclic antidepressant overdose

{{Infobox medical condition (new)
| name            = Tricyclic anti-depressant overdose
| synonyms        = TCA poisoning, TCA overdose, TCA toxicity
| image           = Amitriptyline.svg
| image_size      = 275px
| caption         = Chemical structure of the tricyclic antidepressant [[Chemistry:Amitriptyline|amitriptyline]]
| pronounce       = 
| field           = [[Medicine:Emergency medicine|Emergency medicine]]
| symptoms        = [[Medicine:Hyperthermia|Elevated body temperature]], large pupils, [[Medicine:Heart arrhythmia|irregular heart beat]], seizures<ref name=Kerr2001/>
| onset           = Within 6 hours<ref name=Wo2007/>
| duration        = 
| causes          = Accidental or purposeful<ref name=Wo2007/><ref name=Daz2015/>
| risks           = 
| diagnosis       = 
| differential    = 
| prevention      = 
| treatment       = Supportive, [[Chemistry:Sodium bicarbonate|sodium bicarbonate]], [[Chemistry:Lipid emulsion|lipid emulsion]]<ref name=Wo2007/>
| medication      = 
| frequency       = Relatively common<ref name=Kerr2001/><ref name=Tha2005/>
| deaths          = 270 per year (UK)<ref name=Kerr2001/>
}}

<!-- Definition and symptoms -->
'''Tricyclic antidepressant overdose''' is [[Medicine:Poisoning|poisoning]] caused by excessive medication of the [[Chemistry:Tricyclic antidepressant|tricyclic antidepressant]] (TCA) type. Symptoms may include [[Medicine:Hyperthermia|elevated body temperature]], blurred vision, dilated pupils, sleepiness, confusion, seizures, [[Medicine:Tachycardia|rapid heart rate]], and [[Medicine:Cardiac arrest|cardiac arrest]].<ref name=Kerr2001/> If symptoms have not occurred within six hours of exposure they are unlikely to occur.<ref name=Wo2007/>

<!-- Cause and diagnosis -->
TCA overdose may occur by accident or purposefully in an [[Medicine:Suicide|attempt to cause death]].<ref name=Wo2007/> The toxic dose depends on the specific TCA.<ref name=Wo2007/> Most are non-toxic at less than 5&nbsp;mg/kg except for [[Chemistry:Desipramine|desipramine]], [[Chemistry:Nortriptyline|nortriptyline]], and [[Chemistry:Trimipramine|trimipramine]], which are generally non-toxic at less than 2.5&nbsp;mg/kg.<ref>{{cite journal|first1=Tom|last1=Bartram|title=Best BETs from the Manchester Royal Infirmary. Bet 3. Toxic levels of tricyclic drugs in accidental overdose|journal=Emergency Medicine Journal|date=1 March 2008|issn=1472-0213|pages=166–167|volume=25|issue=3|pmid=18299371|doi=10.1136/emj.2007.056788|s2cid=22419961}}</ref><ref name=Wo2007/> In small children one or two pills can be fatal.<ref name=Ros2005>{{cite journal |vauthors=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> An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.<ref name=Wo2007/>

<!-- Treatment -->
In overdose activated charcoal is often recommended.<ref name=Kerr2001/> People should not be forced to vomit.<ref name=Wo2007/> In those who have a wide [[Medicine:QRS complex|QRS complex]] ({{nowrap|> 100 ms}}) [[Chemistry:Sodium bicarbonate|sodium bicarbonate]] is recommended.<ref name=Wo2007/> If seizures occur benzodiazepines should be given.<ref name=Wo2007/> In those with low blood pressure intravenous fluids and [[Biology:Norepinephrine|norepinephrine]] may be used.<ref name=Kerr2001/> The use of intravenous lipid emulsion may also be tried.<ref name=Daz2015>{{cite journal|first1=Dazhe|last1=Cao|first2=Kennon|last2=Heard|first3=Mark|last3=Foran|first4=Alex|last4=Koyfman|title=Intravenous lipid emulsion in the emergency department: a systematic review of recent literature|journal=The Journal of Emergency Medicine|date=1 March 2015|issn=0736-4679|pages=387–397|volume=48|issue=3|pmid=25534900|doi=10.1016/j.jemermed.2014.10.009}}</ref>

<!-- Epidemiology and history -->
In the early 2000s TCAs were one of the most common cause of poisoning.<ref name=Kerr2001/> In the United States in 2004 there were more than 12,000 cases.<ref name=Wo2007>{{cite journal|first1=Alan D.|last1=Woolf|first2=Andrew R.|last2=Erdman|first3=Lewis S.|last3=Nelson|first4=E. Martin|last4=Caravati|title=Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management|journal=Clinical Toxicology|date=1 January 2007|issn=1556-3650|pages=203–233|volume=45|issue=3|pmid=17453872|doi=10.1080/15563650701226192|first5=Daniel J.|last5=Cobaugh|first6=Lisa L.|last6=Booze|first7=Paul M.|last7=Wax|first8=Anthony S.|last8=Manoguerra|first9=Elizabeth J.|last9=Scharman|first10=Kent R.|last10=Olson|first11=Peter A.|last11=Chyka|first12=Gwenn|last12=Christianson|first13=William G.|last13=Troutman|last14=American Association of Poison Control Centers|s2cid=27172531|doi-access=free}}</ref> In the United Kingdom they resulted in about 270 deaths a year.<ref name=Kerr2001/> An overdose from TCAs was first reported in 1959.<ref name=Kerr2001>{{cite journal |vauthors=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>

==Signs and symptoms==

The peripheral autonomic nervous system, [[Biology:Central nervous system|central nervous system]] and the [[Biology:Heart|heart]] are the main systems that are affected following overdose.<ref name=Kerr2001/> Initial or mild symptoms typically develop within 2 hours and include [[Medicine:Tachycardia|tachycardia]], drowsiness, a dry mouth, nausea and [[Medicine:Vomiting|vomiting]], urinary retention, confusion, agitation, and [[Medicine:Headache|headache]].<ref name="Woolf-2007"/> More severe complications include [[Medicine:Hypotension|hypotension]], cardiac rhythm disturbances, hallucinations, and seizures. Electrocardiogram (ECG) abnormalities are frequent and a wide variety of cardiac dysrhythmias can occur, the most common being [[Medicine:Sinus tachycardia|sinus tachycardia]] and intraventricular conduction delay resulting in prolongation of the [[Medicine:QRS complex|QRS complex]] and the [[Medicine:PR interval|PR]]/[[Medicine:QT interval|QT interval]]s.<ref name=Tha2005>{{cite journal |vauthors=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| s2cid = 44532041 }}</ref> Seizures, cardiac dysrhythmias, and apnea are the most important life-threatening complications.<ref name="Woolf-2007"/>

==Cause==

Tricyclics have a narrow [[Medicine:Therapeutic index|therapeutic index]], ''i.e.'', the therapeutic [[Chemistry:Dose (biochemistry)|dose]] is close to the toxic dose.<ref name="Woolf-2007">{{cite journal |vauthors=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 |volume=45 |issue=3 |pages=203–33 |year=2007 |pmid=17453872 |doi=10.1080/15563650701226192|s2cid=27172531 |doi-access=free }}</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 |vauthors=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 |vauthors=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>

==Pathophysiology==
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have [[Medicine:Anticholinergic|anticholinergic]] effects, cause excessive blockade of [[Biology:Norepinephrine|norepinephrine]] reuptake at the preganglionic [[Biology:Synapse|synapse]], direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having [[Chemistry:Quinidine|quinidine]]-like effects on the myocardium.<ref name=Kerr2001/>

==Diagnosis==
[[File:Electrocardiogram showing QRS widening in patient with TCA overdose.png|thumb|QRS widening seen in a person who has overdosed on TCAs]]
A specific blood test to verify toxicity is not typically available.<ref name=Kerr2001/> An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.<ref name=Wo2007/>

==Treatment==
People with symptoms are usually monitored in an [[Medicine:Intensive care unit|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=Kerr2001/> Supportive therapy is given if necessary, including respiratory assistance and maintenance of body temperature. Once a person has had a normal ECG for more than 24 hours they are generally medically clear.<ref name=Kerr2001/>

===Decontamination===
Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal, which [[Chemistry:Adsorption|adsorbs]] the drug in the [[Biology:Gastrointestinal tract|gastrointestinal tract]] either by mouth 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 |title=Medical toxicology |publisher=Williams & Wilkins| location=Philadelphia |year=2004|pages=834–43| isbn=0-7817-2845-2}}</ref> Other decontamination methods such as stomach pumps, [[Unsolved:Syrup of ipecac|ipecac]] induced emesis, or whole bowel irrigation are generally not recommended in TCA poisoning.<ref name="EmergMedJ2003-Teece">{{cite journal |vauthors=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 |vauthors=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| s2cid = 8482949 }}</ref> Stomach pumps may be considered within an hour of ingestion but evidence to support the practice is poor.<ref name=Kerr2001/><ref>{{cite journal|first1=Stewart|last1=Teece|first2=Kristen|last2=Hogg|title=Gastric lavage in tricyclic antidepressant overdose|journal=Emergency Medicine Journal|date=1 January 2003|issn=1472-0205|pages=64|volume=20|issue=1|pmid=12533375|pmc=1726003|doi=10.1136/emj.20.1.64}}</ref>

===Medication===
Administration of [[Chemistry:Intravenous sodium bicarbonate|intravenous sodium bicarbonate]] as an [[Chemistry:Antidote|antidote]] 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 or [[Chemistry:Magnesium|magnesium]] can be used to reverse any cardiac abnormalities. However, no benefit has been shown from [[Chemistry:Antiarrhythmic agent#Class I agents|Class 1 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 |vauthors=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| s2cid = 7162287 }}</ref> Low blood pressure is initially treated with fluids along with bicarbonate to reverse metabolic acidosis (if present), if the blood pressure remains low despite fluids then further measures such as the administration of epinephrine, [[Biology:Norepinephrine|norepinephrine]], [[Biology:Vasopressin|vasopressin]], or [[Biology:Dopamine|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 [[Chemistry:Benzodiazepine|benzodiazepine]] such as [[Chemistry:Lorazepam|Lorazepam]] or other anticonvulsant may be required for persistent muscular overactivity. [[Chemistry:Barbiturate|Barbiturate]] anticonvulsants are not recommended due to increased risk of respiratory depression. There is no role for [[Chemistry:Physostigmine|physostigmine]] in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures.<ref name=Kerr2001/> In cases of severe TCA overdose that are refractory to conventional therapy, intravenous lipid emulsion therapy has been reported to improve signs and symptoms in moribund patients with toxicities involving several types of lipophilic substances, therefore lipids may have a role in treating severe cases of refractory TCA overdose.<ref>Goldfrank's Toxicological Emergencies 9th Edition</ref>

===Dialysis===
Tricyclic antidepressants are highly protein bound and have a large [[Medicine:Volume of distribution|volume of distribution]]; therefore removal of these compounds from the blood with [[Engineering:Hemodialysis|hemodialysis]], [[Medicine:Hemoperfusion|hemoperfusion]] or other techniques are unlikely to be of any significant benefit.<ref name="toxicolrev2005-dargan"/>

==Epidemiology==

Studies in the 1990s in {{wipe|Australia}} and the {{wipe|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 |vauthors=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|s2cid=38941654 }}</ref><ref name="MedJAust1995-Buckley">{{cite journal |vauthors=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 | doi = 10.5694/j.1326-5377.1995.tb126020.x | pmid = 7877540| s2cid = 7732124 }}</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 [[Chemistry:Amitriptyline|amitriptyline]]. It was determined there were 5.3 deaths per 100,000 prescriptions.<ref>{{cite journal |vauthors=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 |date=October 2001 |pmid=11681546 |doi=10.1017/s0033291701004548|s2cid=23539426 }}</ref>
Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the [[Chemistry:Sodium|Na+]] blockade will increase the [[Medicine:QT interval|QTI]].

==References==
{{Reflist}}

==External links==
{{Medical condition classification and resources
|  DiseasesDB     = 
|  ICD10          = {{ICD10|T|43|0|t|36}} 
|  ICD9           = {{ICD9|969.0}} 
|  ICDO           = 
|  OMIM           = 
|  MedlinePlus    = 
|  eMedicineSubj  = article
|  eMedicineTopic = 1010089
|  MeshID         = 
}}
{{Poisoning and toxicity}}

[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Tricyclic antidepressant overdose}}