Olanzapine Overdose

Olanzapine overdose causes sedation, agitation, anticholinergic effects, tachycardia, extrapyramidal reactions and, in large ingestions, coma and respiratory depression. Deaths are rare and usually involve co-ingestants.

Olanzapine is widely prescribed, and overdose is common. Toxicity appears over about 0.5 mg/kg in children and 100 mg in adults; deaths have been reported above 450 mg, and survival after over 1 g is usual with supportive care.

Risk factors for harm. Co-ingestion with benzodiazepines or alcohol, intramuscular olanzapine with parenteral benzodiazepines, and the pamoate depot preparation (post-injection delirium sedation syndrome).

Course. Peak effects at 4 to 6 hours, and sedation can last up to 24 to 48 hours.

Pathophysiology.

Antagonism of dopamine D2, serotonin 5-HT2, histamine H1, muscarinic and alpha-1 receptors causes sedation, anticholinergic toxicity, extrapyramidal signs and orthostatic hypotension.

• Drowsiness to coma, slurred speech, ataxia and agitation or delirium (paradoxical agitation is common).
• Tachycardia, mydriasis, dry skin, urinary retention and hypotension.
• Extrapyramidal signs: dystonia, rigidity, tremor and akathisia.
• Seizures, hypothermia or hyperthermia, aspiration and respiratory depression in severe cases.

Red flags.

• Glasgow Coma Scale under 9 or hypoventilation.
• Seizures, rigidity with hyperthermia (neuroleptic malignant syndrome).
• QTc over 500 ms.

• History of dose, preparation and co-ingestants; paracetamol and salicylate levels.
• ECG (QTc), glucose, electrolytes, renal function, creatine kinase and venous gas.
• Olanzapine level has no clinical role.
• After depot injection, observe for 3 hours for post-injection delirium sedation syndrome.

Differential diagnosis. Other antipsychotic or sedative overdose, anticholinergic toxicity, neuroleptic malignant syndrome, intoxication with alcohol or opioids and delirium of other cause.

• Airway, breathing and circulation support; most patients need observation and supportive care only.
• 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.
• Agitation: diazepam 5 to 10 mg intravenously, repeated every 5 to 10 minutes as needed. Maximum 30 mg in the first hour without specialist review. Monitor breathing, oxygen saturation and blood pressure. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy. Avoid combining with intramuscular olanzapine.
• 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.
• 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; use supportive care for anticholinergic delirium.
• Observe for at least 6 hours, until alert and ECG is normal.
• Psychiatric assessment in intentional ingestion.

Monitoring. Conscious level, respiratory rate, blood pressure, ECG and temperature until recovery.

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

Special groups. Children: even small doses may cause coma. Older adults: higher risk of aspiration and falls.