Antipsychotic Agent 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, 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

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

Diagnosis

• 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

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 intubated with a cuffed endotracheal tube

• 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 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