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For further information, see CMDT Part 38-58: Tricyclic & Other Antidepressants Overdose

Key Features

  • Tricyclic antidepressants (TCAs) contain both anticholinergic and cardiotoxic properties (quinidine-like sodium channel blockade)

  • Newer generation antidepressants

    • Trazodone, fluoxetine, citalopram, paroxetine, sertraline, bupropion, venlafaxine, and fluvoxamine

    • Not chemically related to the TCAs

    • With the exception of bupropion, do not generally produce cardiotoxic effects

    • May cause seizures and serotonin syndrome (see Monoamine Oxidase Inhibitor Overdose) in overdoses

Clinical Findings

  • Severe symptoms may occur abruptly within 30–60 min after acute tricyclic antidepressant overdose

    • Anticholinergic effects

      • Dilated pupils

      • Tachycardia

      • Dry mouth

      • Flushed skin

      • Muscle twitching

      • Decreased peristalsis

    • Quinidine-like cardiotoxic effects

      • QRS interval widening (> 0.12 s)

      • Ventricular arrhythmias

      • Atrioventricular block

      • Hypotension

    • Seizures and coma are common with severe intoxication

  • Prolongation of the QT interval and torsades de pointes have been reported with several of the newer antidepressants

  • Life-threatening hyperthermia may result from status epilepticus and anticholinergic-induced impairment of sweating

  • 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


  • QRS interval correlates with the severity of tricyclic intoxication more reliably than the serum drug level

  • Late upward R-wave in aVR is also commonly seen


  • Observe patients for at least 6 h

  • Admit patients if there are anticholinergic effects or signs of cardiotoxicity

  • Administer activated charcoal 60–100 g mixed in aqueous slurry orally or via gastric tube

  • Consider gastric lavage after recent large ingestions

  • Treat cardiotoxic effects with boluses of sodium bicarbonate (50–100 mEq intravenously)

    • Maintain the pH between 7.45 and 7.50

    • Alkalinization does not promote excretion of TCAs

  • Prolongation of the QT interval or torsades de pointes is usually treated with intravenous magnesium or overdrive pacing

  • Severe cardiotoxicity in patients with overdoses of lipid-soluble drugs (eg, amitriptyline, bupropion) has responded to intravenous lipid emulsion (Intralipid), 1.5 mL/kg repeated one to two times if needed

  • Plasma exchange using albumin and extracorporeal membrane oxygenation (ECMO) has been reported successful in several cases

  • Serotonin syndrome

    • Mild: may be treated with benzodiazepines and withdrawal of the antidepressant

    • Moderate: may respond to cyproheptadine (4 mg orally or via gastric tube hourly for three or four doses) or chlorpromazine 25 mg intravenously

  • Severe hyperthermia should be treated with neuromuscular paralysis and endotracheal intubation in addition to external cooling measures

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