What is the management for an adult patient with a history of psychiatric illness, such as schizophrenia or bipolar disorder, who has overdosed on olanzapine (atypical antipsychotic)?

Management of Olanzapine Overdose

Olanzapine overdose requires immediate supportive care with focus on airway protection, cardiovascular monitoring, and management of anticholinergic toxicity, with no specific antidote available for routine use. 1

Immediate Assessment and Stabilization

Airway and Respiratory Management

• Intubate patients with Glasgow Coma Scale ≤8 or those unable to protect their airway, as CNS depression is the predominant feature of olanzapine toxicity 2, 3
• Mechanical ventilation may be required for 7-44 hours in severe cases, with consciousness disturbances potentially lasting up to 6 days 3
• Monitor respiratory rate closely in non-intubated patients, as respiratory depression can occur particularly when benzodiazepines or other CNS depressants are co-ingested 4

Cardiovascular Monitoring

• Expect tachycardia (present in 85% of cases) and hypertension (73% of cases) as the most common cardiovascular manifestations 3
• Monitor for QTc prolongation, though this occurs in only 1% of cases at therapeutic doses 5
• Paradoxically, both hypertension and hypotension can occur; hypotension is less common (2%) but requires fluid resuscitation when present 5
• Continuous cardiac monitoring is essential, as heart rates can reach 138-160 beats/minute 2, 3

Neurological Management

Consciousness Disturbances

• Coma occurs in 54% of olanzapine overdoses and is graded by Matthew's scale: Grade III (deep coma) is most common at 50%, followed by Grade II (23%) 3
• Mean duration of consciousness disturbances is 45 hours, but can persist for up to 6 days in severe cases 3
• Psychomotor agitation paradoxically occurs in 81% of cases, often alternating with sedation 3

Seizure Management

• Generalized tonic-clonic seizures can occur and should be treated with standard anticonvulsant therapy 6
• Monitor for cerebral edema in severe cases, particularly if seizures are present or consciousness does not improve as expected 6

Anticholinergic Toxicity

• Miosis occurs in 65% of cases (contrary to typical anticholinergic mydriasis), though mydriasis can also occur 3
• Dry skin, dry mucous membranes, and decreased bowel sounds are common anticholinergic features 7
• Delirium is a prominent feature requiring close monitoring and behavioral management 2

Specific Interventions

Physostigmine Consideration

• Physostigmine (0.5-2 mg IV) may transiently reverse delirium and mental status changes in pure olanzapine overdose, but its routine use remains controversial 7
• Response is typically temporary (30 minutes), and repeated dosing may be required 7
• Only consider in confirmed pure olanzapine overdose without co-ingestion of other medications or substances 7
• Do not use physostigmine if QTc prolongation, seizures, or cardiovascular instability are present

Cerebral Edema Management

• Administer IV mannitol if head CT reveals cerebral edema or if intracranial pressure is elevated 6
• Consider head CT in patients with prolonged coma (>24 hours), persistent seizures, or focal neurological findings 6
• Cranial pressure-lowering treatment has demonstrated effectiveness in improving outcomes 6

Metabolic Complications

• Monitor blood glucose every 4-6 hours, as hyperglycemia occurs frequently (glucose can reach 350 mg/dL) 2
• Administer insulin for glucose >200 mg/dL using standard hyperglycemia protocols 2
• Monitor creatine phosphokinase for rhabdomyolysis (can reach 1992 mg/dL) 2
• Correct metabolic acidosis with supportive care and fluid resuscitation 2

Decontamination and Elimination

Gastrointestinal Decontamination

• Activated charcoal (50g) may be considered if patient presents within 1-2 hours of ingestion and can protect airway 3
• Do not administer activated charcoal to obtunded patients without secured airway 3

Enhanced Elimination

• No role for hemodialysis or hemoperfusion, as olanzapine has high protein binding and large volume of distribution 2
• Supportive care remains the mainstay of treatment 1, 3

Monitoring Parameters

Laboratory Monitoring

• Serum olanzapine concentration if available (therapeutic range 20-80 ng/mL; toxic >100 ng/mL; severe toxicity >1000 ng/mL) 2, 7, 3
• Complete blood count (leukocytosis is common) 2
• Comprehensive metabolic panel including glucose, electrolytes, and renal function 2
• Creatine phosphokinase for rhabdomyolysis 2
• Arterial blood gas if respiratory compromise or metabolic acidosis suspected 2

Clinical Monitoring

• Continuous cardiac telemetry with QTc monitoring 5
• Vital signs every 15-30 minutes until stable, then hourly 3
• Glasgow Coma Scale and neurological examination every 1-2 hours 3
• Temperature monitoring (both hyperthermia and hypothermia can occur) 3

Special Considerations

Neuroleptic Malignant Syndrome

• Immediately discontinue olanzapine if NMS is suspected (hyperpyrexia, muscle rigidity, altered mental status, autonomic instability) 1
• NMS occurs in 2% of high-dose olanzapine cases and can be fatal 5
• Provide intensive supportive care with cooling measures, IV fluids, and consider dantrolene or bromocriptine 1

Extrapyramidal Symptoms

• Extrapyramidal symptoms occur in 27% of high-dose cases, higher than expected for an atypical antipsychotic 5
• Treat with benztropine or diphenhydramine if severe 5

Co-Ingestions

• Benzodiazepine co-ingestion dramatically increases risk of respiratory depression and mortality 4
• 50% of olanzapine overdose patients have co-ingested other medications, and 23% have consumed alcohol 3
• Adjust management based on toxidrome of co-ingested substances 3

Disposition and Prognosis

Expected Course

• Mean hospitalization duration is 5.7 days 3
• 50% of cases are classified as severe poisoning (PSS 3) 3
• Fatal outcomes are rare but have been documented, particularly with co-ingestion of benzodiazepines or doses >600 mg 4, 7
• Maximum daily doses up to 160 mg have been associated with increased frequency of extrapyramidal symptoms, sedation, and severe toxicity 5

ICU Admission Criteria

• Glasgow Coma Scale ≤12 3
• Requiring intubation or mechanical ventilation 2
• Hemodynamic instability 2
• Seizures or suspected cerebral edema 6
• QTc >500 msec 5