Tricyclic antidepressant overdose

The peripheral autonomic nervous system, central nervous system and the heart are the main systems that are affected following overdose. 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. More severe complications include 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 sinus tachycardia and intraventricular conduction delay resulting in prolongation of the QRS complex and the PR/QT intervals.{{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 }} Seizures, cardiac dysrhythmias, and apnea are the most important life-threatening complications.

Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose.{{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 }} Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.{{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}} However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.{{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}}

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.

File:Electrocardiogram showing QRS widening in patient with TCA overdose.png

A specific blood test to verify toxicity is not typically available. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.

People with symptoms 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. 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.

Initial treatment of an acute overdose includes gastric decontamination. This is achieved by giving activated charcoal, which adsorbs the drug in the gastrointestinal tract either by mouth or via a nasogastric tube. Activated charcoal is most useful if given within 1 to 2 hours of ingestion.{{cite book |last=Dart| first= RC |title=Medical toxicology |publisher=Williams & Wilkins| location=Philadelphia |year=2004|pages=834–43| isbn=0-7817-2845-2}} Other decontamination methods such as stomach pumps, ipecac induced emesis, or whole bowel irrigation are generally not recommended in TCA poisoning.{{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}}{{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 }} Stomach pumps may be considered within an hour of ingestion but evidence to support the practice is poor.{{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}}

Administration of intravenous sodium bicarbonate as an 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 magnesium can be used to reverse any cardiac abnormalities. However, no benefit has been shown from 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.{{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 }} 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, norepinephrine, vasopressin, or dopamine can be used to increase blood pressure.

Another potentially severe symptom is seizures: Seizures often resolve without treatment but administration of a benzodiazepine such as Lorazepam or other anticonvulsant may be required for persistent muscular overactivity. Barbiturate anticonvulsants are not recommended due to increased risk of respiratory depression. There is no role for physostigmine in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures. 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.Goldfrank's Toxicological Emergencies 9th Edition

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.

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.{{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|bibcode=1996HETox..15..466T |s2cid=38941654 }}{{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 }} 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.{{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 }}

Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the Na+ blockade will increase the QTI.

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{{Medical condition classification and resources

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| ICD10 = {{ICD10|T|43|0|t|36}}

| ICD9 = {{ICD9|969.0}}

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| eMedicineTopic = 1010089

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Category:Poisoning by drugs, medicaments and biological substances

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