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For further information, see CMDT Part 38-21: Antipsychotic Drug Overdose

Key Features

  • Conventional antipsychotics act mainly on CNS dopamine receptors; examples include

    • Chlorpromazine

    • Haloperidol

    • Droperidol

  • Newer "atypical" antipsychotics also interact with serotonin receptors; examples include

    • Risperidone

    • Olanzapine

    • Ziprasidone

    • Quetiapine

    • Aripiprazole

Clinical Findings

  • Drowsiness, orthostatic hypotension

  • Large overdose

    • Miosis

    • Severe hypotension

    • Tachycardia

    • Convulsions

    • Obtundation or coma

  • Prolongation of QRS interval or QT interval or both and ventricular arrhythmias

  • An acute extrapyramidal dystonic reaction may occur with therapeutic or toxic doses

    • Spasmodic contractions of the face and neck muscles, extensor rigidity of the back muscles, carpopedal spasm, and motor restlessness

    • More common with haloperidol and other butyrophenones, less common with atypical drugs

  • Severe rigidity, hyperthermia, and metabolic acidosis (neuroleptic malignant syndrome) may occasionally occur and are life-threatening

  • Atypical antipsychotics have also been associated with weight gain and diabetes mellitus, including diabetic ketoacidosis


  • Largely based on history of exposure

  • Most agents are not detected in routine rapid toxicology screens

  • Serum levels are not helpful

  • ECG monitoring for QRS, QT prolongation


  • Activated charcoal for large or recent ingestions

  • Widened QRS interval

    • Seen in thioridazine poisoning

    • May respond to intravenous NaHCO3 as used for tricyclic antidepressants

  • Hypotension often responds to intravenous saline boluses; cardiac arrhythmias associated with widened QRS intervals on the ECG may respond to intravenous sodium bicarbonate as is given for tricyclic antidepressant overdoses

  • Prolonged QT interval or torsades de pointes, or both

    • Magnesium 1–2 g intravenously

    • Consider overdrive pacing

  • Treat hyperthermia, maintain cardiac monitoring

  • For extrapyramidal signs

    • Diphenhydramine, 0.5–1.0 mg/kg intravenously, or benztropine mesylate, 0.01–0.02 mg/kg intramuscularly

    • Continue with oral doses for 24–48 hours

  • Bromocriptine (2.5–7.5 mg daily orally) may be effective for mild or moderate neuroleptic malignant syndrome

  • Dantrolene (2–5 mg/kg intravenously) has also been used for muscle contractions but is not a true antidote

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