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Key Features

  • Antipsychotic drugs

    • Phenothiazines (chlorpromazine, prochlorperazine, promethazine)

    • Butyrophenones (haloperidol, droperidol)

    • New "atypical" drugs (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, lurasidone)

Clinical Findings

  • Drowsiness, orthostatic hypotension, especially with α-blocking agents

  • Large overdose

    • Miosis

    • Severe hypotension

    • Tachycardia

    • Convulsions

    • Obtundation or coma

  • Prolongation of QRS interval (thioridazine) or QT interval (with possible torsades de pointes)

  • 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 butyrophenones, less common with atypical drugs

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

Diagnosis

  • Largely based on history of exposure

  • Most agents are not detected in routine rapid toxicology screens

  • Serum levels not helpful

  • ECG monitoring for QRS, QT prolongation

Treatment

  • Activated charcoal

    • Give 60–100 g (in aqueous slurry) orally or via gastric tube

    • Do not use for comatose or convulsing patients unless they are endotracheally intubated

  • Widened QRS interval

    • Seen in thioridazine poisoning

    • May respond to intravenous NaHCO3 as used for tricyclic antidepressants

  • 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 1–2 days

  • 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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