, Volume 23, Issue 6, pp 431–461 | Cite as

Antidepressant Overdosage

  • Peter Crome
Review Articles


Deliberate self-poisoning with antidepressant drugs has become an increasingly common problem. Toxicologically, antidepressants can be subdivided into 4 groups: (a) tricyclic antidepressants (including maprotiline); (b) monoamine oxidase inhibitors; (c) lithium; and (d) a miscellaneous group which includes several new antidepressants.

Tricyclic antidepressants account for most of the hospital admissions and deaths resulting from antidepressant poisoning. They have complex pharmacological actions on the central nervous system, the heart and the parasympathetic nervous system which account for the varied clinical features of tricyclic antidepressant overdose. Symptoms usually appear within 4 hours of an overdose, the most common complications being dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and either drowsiness or excitement. In severe poisoning, hypotension, convulsions, coma, respiratory depression and electrocardiographic abnormalities may all occur. The most frequent electrocardiographic abnormalities are sinus tachycardia with a prolonged PR interval and a widened QRS complex. The ECG changes may resemble ventricular or supraveniricular tachycardia or bundle branch block. Atrioventricular block and bradycardia are also seen in severe poisoning. The more serious effects of tricyclic antidepressants on the heart are probably due to a quinidine- like myocardial depressant action. There is little evidence to suggest that tricyclic antidepressants differ in their toxicity except perhaps that maprotiline causes convulsions more frequently than other drugs. Treatment is essentially supportive. Gastric aspiration and lavage should be performed if less than 12 hours have elapsed since the overdose. Acidosis and hypoxia should be corrected. Convulsions should be treated with either chlormethiazole or diazepam with early recourse to artificial ventilation if these fail. Cardiotoxicity will only require specific drug treatment if there is evidence of circulatory failure (cold peripheries, poor urine output, etc). β-Stimulants should be tried before antiarrhythmic drugs because the latter agents may depress myocardial contractility still further. Sodium bicarbonate should be tried in the treatment of arrhythmias even in the absence of acidosis. There is no objective evidence that active elimination techniques are effective and they should not be used. Physostigmine will reverse most of the complications of tricyclic antidepressant overdose, but its effect is short-lasting and it may produce potentially serious side effects; it should be reserved for patients with complications of coma or those with convulsions or cardiotoxicity resistant to other treatments. Plasma drug estimation may be useful in patients with severe, unusual or prolonged symptoms and in those in whom the diagnosis is uncertain.

Monoamine oxidase inhibitors are now taken far less frequently than tricyclic antidepressants, both therapeutically and in overdose. Monoamine oxidase inhibitor overdose may result in excitement, tachycardia, tachypnoea, hyperpyrexia, coma, convulsions, and either hypo- or hypertension, usually after a delay of 12 hours or more. Treatment is supportive and there is no evidence that active elimination techniques are helpful. Excitement should be treated with chlorpromazine or diazepam, and chlorpromazine is also useful in controlling hyperpyrexia. Hypertension should be treated cautiously with α-adrenoceptor blockers and hypotension with plasma expanders. Care should be taken to ensure that the drugs used in treatment do not interact adversely with monoamine oxidase inhibitors.

Acute over dosage with lithium only rarely results in serious consequences. Initial symptoms may be delayed for 12 to 24 hours. Agitation, weakness of the limbs, tremor, fasciculation and rigidity are common complications, and coma, convulsions, hypotension and renal failure may occur in serious cases. Treatment is supportive, and special attention should be given to fluid balance and electrolyte disturbance. Patients with plasma lithium levels above 3.0mmol/L and those with severe symptoms are best treated by haemodialysis which may have to be repeated if there is a secondary rise in the plasma concentration.

The miscellaneous group of antidepressants all differ from each other in both chemical structure and pharmacological properties. The most information is available about mianserin, which when taken alone appears to produce drowsiness, without serious toxic effects. Similarly, serious complications have not been reported with either nomifensine or flupenthixol overdose. However, little or no data are available on the effects of over dosage with these newer agents in ‘at risk’ patients — for example, those with pre-existing heart disease. I patient who took an overdose of nomifensine developed haemolytic anaemia, but this has also been reported during therapeutic use of the drug. There is too little information about acute overdose with iprindole, tofenacin, trazodone or viloxazine to draw any conclusions about their relative toxicity.


Imipramine British Medical Journal Activate Charcoal Physostigmine Mianserin 
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Copyright information

© ADIS Press Australasia Pty Ltd 1982

Authors and Affiliations

  • Peter Crome
    • 1
  1. 1.Poisons UnitGuy’s HospitalLondonEngland

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