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Tricyclic and related cyclic antidepressants are among the most dangerous drugs involved in suicidal overdose. These drugs have anticholinergic and cardiac depressant properties (“quinidine-like” sodium channel blockade). Tricyclic antidepressants produce more marked membrane-depressant cardiotoxic effects than the phenothiazines.

Newer-generation antidepressants such as trazodone, fluoxetine, citalopram, paroxetine, sertraline, bupropion, venlafaxine, and fluvoxamine are not chemically related to the tricyclic antidepressant agents and, with the exception of bupropion, do not generally produce quinidine-like cardiotoxic effects. However, they may cause seizures in overdoses and they may cause serotonin syndrome (see Monoamine Oxidase Inhibitors section).


Signs of severe intoxication may occur abruptly and without warning within 30–60 minutes after acute tricyclic overdose. Anticholinergic effects include dilated pupils, tachycardia, dry mouth, flushed skin, muscle twitching, and decreased peristalsis. Quinidine-like cardiotoxic effects include QRS interval widening (greater than 0.12 s; Figure 38–2), ventricular arrhythmias, AV block, and hypotension. Rightward-axis deviation of the terminal 40 ms of the QRS has also been described. Prolongation of the QT interval and torsades de pointes have been reported with several of the newer antidepressants. Seizures and coma are common with severe intoxication. Life-threatening hyperthermia may result from status epilepticus and anticholinergic-induced impairment of sweating. Among newer agents, bupropion and venlafaxine have been associated with a greater risk of seizures.

Figure 38–2.

Cardiac arrhythmias resulting from tricyclic antidepressant overdose. A: Delayed intraventricular conduction results in prolonged QRS interval (0.18 s). B and C: Supraventricular tachycardia with progressive widening of QRS complexes mimics ventricular tachycardia. (Reproduced, with permission, from Benowitz NL, Goldschlager N. Cardiac disturbances in the toxicologic patient. In: Haddad LM, Winchester JF [editors], Clinical Management of Poisoning and Drug Overdose, 3rd edition. Saunders/Elsevier, 1998. Copyright © Elsevier.)

The diagnosis should be suspected in any overdose patient with anticholinergic side effects, especially if there is widening of the QRS interval or seizures. For intoxication by most tricyclic antidepressants, the QRS interval correlates with the severity of intoxication more reliably than the serum drug level.

Serotonin syndrome should be suspected if agitation, delirium, diaphoresis, tremor, hyperreflexia, clonus (spontaneous, inducible, or ocular), and fever develop in a patient taking serotonin reuptake inhibitors.


A. Emergency and Supportive Measures

Observe patients for at least 6 hours and admit all patients with evidence of anticholinergic effects (eg, delirium, dilated pupils, tachycardia) or signs of cardiotoxicity.

Administer activated charcoal and consider gastric lavage after recent large ingestions. All of these drugs have large volumes of distribution and are not effectively removed by hemodialysis procedures.

B. Specific Treatment

Cardiotoxic sodium channel–depressant effects of tricyclic antidepressants may respond to boluses of sodium bicarbonate (50–100 mEq intravenously). Sodium bicarbonate provides a large sodium load that alleviates depression of ...

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