Quetiapine Overdose

Quetiapine overdose causes profound sedation, tachycardia, hypotension and QT prolongation, and may cause seizures and cardiac arrest in large ingestions. It is one of the commonest antipsychotics taken in overdose and the commonest cause of antipsychotic related deaths.

Serious toxicity is seen above 3 g in adults, with coma and respiratory depression likely above 6 g, and fatalities reported at around 10 g. Children can be seriously affected by small doses.

Risk factors for harm. Extended release preparations, co-ingestion with sedatives and alcohol, and cardiac disease.

Course. Peak effects at 2 to 6 hours (up to 12 hours for extended release), with coma lasting 24 to 48 hours in severe cases.

Pathophysiology.

Blockade of histamine H1, alpha-1 adrenergic and muscarinic receptors causes sedation, vasodilatation with hypotension, reflex tachycardia and anticholinergic effects.

Potassium channel blockade prolongs the QT interval.

• Drowsiness progressing to coma, respiratory depression and loss of airway reflexes.
• Tachycardia and hypotension, sometimes refractory.
• QT prolongation, torsades de pointes, wide complex rhythms and seizures.
• Anticholinergic features: dry mouth, mydriasis, urinary retention and delirium on waking.
• Hypothermia and rhabdomyolysis in some.

Red flags.

• Glasgow Coma Scale under 9, apnoea or hypoxia.
• Refractory hypotension, QTc over 500 ms or arrhythmia.
• Seizures.

• History of dose, formulation, time and co-ingestants; paracetamol and salicylate levels.
• ECG on arrival and repeated at 4 and 8 hours (QTc); continuous monitoring.
• Electrolytes (potassium, magnesium, calcium), glucose, renal function, creatine kinase, venous gas with lactate.
• Quetiapine can cause false positive tricyclic antidepressant and methadone screens on urine immunoassays.

Differential diagnosis. Other antipsychotic or sedative overdose (olanzapine, clozapine), tricyclic antidepressant overdose, opioid overdose, benzodiazepine overdose and structural brain disease.

• Airway protection and ventilation for reduced consciousness or hypoxia.
• 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 without a protected airway, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Hypotension: intravenous 0.9% sodium chloride 10 to 20 mL/kg in boluses, then noradrenaline 0.05 micrograms/kg/minute intravenously, titrated to a mean arterial pressure of 65 mmHg or higher. Maximum 1 microgram/kg/minute. Give by central line; monitor blood pressure, extravasation and arrhythmia; use caution in cardiac disease. Avoid adrenaline and dopamine, which can worsen vasodilatation.
• Torsades de pointes or QTc over 500 ms: correct potassium to over 4.0 mmol/L, and give 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. Use overdrive pacing or isoprenaline for recurrent torsades (specialist); defibrillate for pulseless arrhythmia.
• 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.
• Avoid physostigmine and antiarrhythmics that prolong QT (amiodarone, class 1A and 1C drugs).
• Urinary retention: catheterise. Hypothermia: external rewarming.
• Observe for at least 6 hours (12 to 24 hours for extended release or large ingestions), with a normal ECG and alert state before discharge.
• Psychiatric assessment in intentional ingestion.

Monitoring. Continuous ECG, blood pressure and oxygen saturation; QTc every 4 to 6 hours; electrolytes and creatine kinase.

Referral and escalation. Poisons information centre; intensive care for coma, hypotension or arrhythmia.

Special groups. Children: even small ingestions need observation. Pregnancy: the same treatment applies.