Risperidone Overdose

Risperidone overdose causes sedation, tachycardia, hypotension, extrapyramidal reactions and, in large ingestions, QT prolongation and seizures. Deaths are rare, and most patients recover with supportive care.

Risperidone is a commonly prescribed second generation antipsychotic. Toxicity is likely above 20 mg in adults and above 0.5 mg/kg in children; severe effects are seen above 100 mg.

Risk factors for harm. Co-ingestants, cardiac disease, electrolyte disturbance and young age.

Course. Peak effects at 1 to 6 hours; the active metabolite (paliperidone) extends effects to 24 to 48 hours. Long acting injections release over weeks.

Pathophysiology.

Potent blockade of dopamine D2, serotonin 5-HT2A and alpha-1 receptors causes extrapyramidal signs and orthostatic hypotension, with QT prolongation at high concentrations.

• Drowsiness, dystonia, tremor, rigidity, agitation and slurred speech.
• Tachycardia, hypotension, QT prolongation and wide QRS.
• Seizures, hyperprolactinaemia, hypothermia or hyperthermia, and coma in severe cases.

Red flags.

• QTc over 500 ms, wide QRS or syncope.
• Seizures or coma.
• Rigidity with fever.

• History of dose, formulation and co-ingestants; paracetamol and salicylate levels.
• ECG on arrival and repeated at 4 to 6 hours; electrolytes, glucose, renal function and creatine kinase.
• Drug levels are not useful.

Differential diagnosis. Other antipsychotic overdose, tricyclic antidepressant overdose, neuroleptic malignant syndrome, serotonin toxicity and sedative overdose.

• Supportive care with continuous ECG monitoring; correct potassium and magnesium.
• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Acute dystonia: procyclidine 5 mg intravenously or intramuscularly, repeated after 20 minutes if needed. Maximum 20 mg in 24 hours. Monitor heart rate, confusion and urinary retention. Avoid in glaucoma, gastrointestinal obstruction and urinary retention; use lower doses in older adults.
• Hypotension: intravenous fluids, then noradrenaline 0.05 micrograms/kg/minute intravenously if needed, titrated to a mean arterial pressure of 65 mmHg or higher (maximum 1 microgram/kg/minute; central line; monitor blood pressure and extravasation). Avoid adrenaline.
• Torsades de pointes: magnesium sulphate 2 g (8 mmol) intravenously over 10 minutes, repeated once if needed. Maximum 4 g in the first hour. Monitor reflexes, respiratory rate and magnesium; reduce dose in renal impairment.
• QRS over 100 ms: sodium bicarbonate 8.4% 1 to 2 mmol/kg (1 to 2 mL/kg) intravenously over several minutes, repeated until QRS is under 100 ms. Maximum serum pH 7.55 and sodium 150 mmol/L. Monitor ECG, pH, potassium and sodium.
• Seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if seizures continue. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• Agitation: reassurance and low dose diazepam 5 mg intravenously, repeated as needed (maximum 30 mg in the first hour without specialist review; monitor breathing and sedation).
• Observe for at least 6 hours; 24 hours for large ingestions or ECG changes.
• Psychiatric assessment in intentional ingestion.

Monitoring. ECG, conscious level, blood pressure and temperature; creatine kinase if rigid.

Referral and escalation. Poisons information centre for large ingestions; intensive care for coma, arrhythmia or seizures.

Special groups. Children: acute dystonia and sedation after small doses. Older adults: caution because of dementia related risks.