What is the treatment for an olanzapine (atypical antipsychotic) overdose?

Management of Olanzapine Overdose

The primary treatment for olanzapine overdose includes activated charcoal administration (if within 1-6 hours of ingestion), supportive care with airway management, and monitoring for complications such as CNS depression, anticholinergic toxicity, and metabolic disturbances. 1, 2

Initial Assessment and Stabilization

• Assess and secure airway, breathing, and circulation as olanzapine overdose commonly causes CNS depression that may require intubation and mechanical ventilation 2, 3
• Monitor vital signs with particular attention to heart rate (tachycardia is common), blood pressure (hypotension may occur), respiratory rate, and temperature 4
• Obtain baseline laboratory studies including complete blood count, comprehensive metabolic panel, creatine phosphokinase, and blood glucose (hyperglycemia is a common finding) 4, 3
• Consider ECG monitoring for QTc prolongation, though this is less common than with other antipsychotics 4, 5

Specific Interventions

Gastrointestinal Decontamination

• Administer activated charcoal (1 g/kg) if the patient presents within 1-6 hours of ingestion and has a protected airway 1
• Activated charcoal reduces the Cmax and AUC of oral olanzapine by approximately 60%, making it particularly effective for olanzapine overdose 1
• Multiple-dose activated charcoal is not recommended as olanzapine does not undergo significant enterohepatic recirculation 1

Management of Anticholinergic Toxicity

• Monitor for and treat anticholinergic symptoms including tachycardia, hyperthermia, dry mucous membranes, urinary retention, and delirium 2
• Benzodiazepines (lorazepam 0.5-2 mg IV every 6 hours) may be used to manage agitation and delirium 6
• Physostigmine is generally not recommended for olanzapine-induced anticholinergic toxicity due to risk of seizures and cardiac arrhythmias 4

Management of CNS Depression

• Position patient to protect airway; intubation may be necessary in severe cases 7, 3
• Avoid medications that may further depress the CNS 1
• For patients with cerebral edema (rare complication), consider mannitol administration and neurosurgical consultation 2

Management of Metabolic Disturbances

• Monitor blood glucose frequently and treat hyperglycemia with insulin if needed 4, 3
• Monitor for metabolic acidosis and correct electrolyte abnormalities 4
• Monitor creatine phosphokinase for evidence of rhabdomyolysis 4, 5

Monitoring and Supportive Care

• Continuous cardiac monitoring for at least 24 hours in symptomatic patients 5
• Monitor for extrapyramidal symptoms which may appear 24-72 hours after ingestion 7, 5
• Provide IV fluids to maintain adequate hydration and blood pressure 4, 3
• Monitor for seizures, which although rare, may occur in severe overdoses 2, 7

Special Considerations

• Avoid medications with anticholinergic properties as they may worsen anticholinergic toxicity 1
• Use caution with benzodiazepines as co-administration may increase somnolence 1
• Avoid dopamine antagonists (metoclopramide, phenothiazines, haloperidol) to prevent excessive dopamine blockade 6
• No specific antidote exists for olanzapine overdose; treatment is primarily supportive 3

Prognosis and Disposition

• Most patients with olanzapine overdose recover fully with supportive care 7, 3
• Admission to an intensive care unit is recommended for patients with significant symptoms 4, 5
• Psychiatric evaluation should be considered prior to discharge for intentional overdoses 7
• Even very high doses (up to 400 mg in adolescents and 180 mg in young children) have been survived with appropriate supportive care 7, 3

Breakthrough Treatment for Olanzapine-Induced Nausea/Vomiting

For patients taking therapeutic doses of olanzapine who experience breakthrough nausea/vomiting:

• Consider alternative antiemetics such as 5-HT3 antagonists (ondansetron), benzodiazepines (lorazepam), or dexamethasone 6
• Avoid other dopamine antagonists when possible to prevent excessive dopamine blockade 6