olanzapine
atypical antipsychotic· Brands: Zyprexa, Zyprexa Velotab, Olanzapine TevaIMPO
Mechanism of action
Olanzapine is a thienobenzodiazepine that acts as an antagonist at multiple receptors, including dopamine D2 and serotonin 5-HT2A receptors. It also has antagonist activity at muscarinic, histaminic (H1), and adrenergic (alpha-1) receptors. The antipsychotic effect is thought to be mediated primarily through D2 and 5-HT2A blockade, while the broader receptor profile contributes to its side effects, such as sedation and anticholinergic effects.
Pharmacokinetics
Olanzapine is well absorbed after oral administration, with peak plasma concentrations occurring within 5 to 8 hours. It undergoes extensive first-pass metabolism, primarily via cytochrome P450 1A2 and 2D6. The mean elimination half-life is 30 hours, allowing once-daily dosing. Metabolism is influenced by smoking (induces CYP1A2) and by inhibitors of CYP1A2 (e.g., fluvoxamine). Olanzapine is widely distributed and approximately 93% bound to plasma proteins.
Indications & dosing
Schizophrenia
Initial dose 10 mg daily; titrate to response.
- adult · PO: 5–20 mg/day once daily · Initial dose 10 mg daily; titrate to response.
Bipolar mania
Initial dose 10-15 mg daily.
- adult · PO: 5–20 mg/day once daily · Initial dose 10-15 mg daily.
Bipolar maintenance
Initial dose 10 mg daily; adjust based on response.
- adult · PO: 5–20 mg/day once daily · Initial dose 10 mg daily; adjust based on response.
Acute agitation (intramuscular)
Avoid benzodiazepines concurrently; monitor for respiratory depression.
- adult · IM: 5–10 mg PRN, repeat after 2h · Avoid benzodiazepines concurrently; monitor for respiratory depression.
Contraindications & precautions
- Known hypersensitivity to olanzapine · Hypersensitivity reactions include rash, angioedema, and anaphylaxis.
- Narrow-angle glaucoma · Due to anticholinergic effects; caution is advised in patients with narrow-angle glaucoma.
- Prostatic hypertrophy · Anticholinergic effects may worsen urinary retention.
- Use with caution in patients with cardiovascular disease, including heart failure, hypertension, and arrhythmias, due to risk of orthostatic hypotension and QT prolongation.
- Monitor for signs of metabolic syndrome, including weight gain, hyperglycaemia, and dyslipidaemia; regular screening of blood glucose and lipids is recommended.
- Caution in elderly patients with dementia-related psychosis: increased risk of cerebrovascular events and mortality.
- Reduce dose or use with caution in patients with hepatic impairment, or those with significant renal impairment.
- Avoid alcohol and other CNS depressants, as they may potentiate sedation and hypotension.
- Caution in patients with a history of seizures or epilepsy, as olanzapine may lower the seizure threshold.
Adverse effects
- Weight gain and increased appetite
- Somnolence
- Constipation and dry mouth
- Orthostatic hypotension
- Dyslipidemia (especially hypertriglyceridemia)serious
- Hyperglycaemia and new-onset diabetes mellitusserious
- Extrapyramidal symptoms (tardive dyskinesia, parkinsonism)serious
- Neuroleptic malignant syndromeserious
- QT prolongationserious
- Seizures (especially in patients with epilepsy or risk factors)serious
Interactions
- fluoxetinemoderateIf the combination is initiated, consider a lower starting dose of olanzapine and monitor for signs of excessive sedation, weight gain, metabolic changes, and extrapyramidal symptoms. If fluoxetine is discontinued, monitor for reduced olanzapine efficacy and consider adjusting the olanzapine dose. Individualise treatment based on clinical response and tolerability.
Renal & hepatic adjustment
- Hepatic impairment (moderate): In hepatic impairment, the initial dose is 5 mg once daily. Increase dose cautiously, with monitoring for adverse effects. Use with caution in severe hepatic impairment.
Monitoring, pregnancy & toxicity
- Weight and BMI · Baseline, then at 4, 8, 12 weeks, then every 3 months
- Fasting blood glucose and HbA1c · Baseline, then at 3 months and annually; more often if diabetic or high risk
- Lipid profile · Baseline, then at 3 months and annually
- Blood pressure · Baseline and periodically
- Extrapyramidal symptoms · During titration and regularly, especially in elderly
- Mental state · Each contact
- Pregnancy: Use in pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. There is evidence of risk of neonatal withdrawal symptoms and extrapyramidal signs if used in the third trimester. Specialist advice should be sought.
- Toxicity: CNS depression (drowsiness, coma) · Supportive care, monitoring of vital signs, airway protection
- Toxicity: Hypotension · IV fluids, vasopressors if needed
- Toxicity: Anticholinergic effects (dry mouth, constipation, urinary retention) · Symptomatic treatment
- Toxicity: Cardiac arrhythmias (QT prolongation) · Continuous ECG monitoring, avoid other QT-prolonging drugs; consider magnesium if torsades
Clinical notes
Olanzapine is used for the treatment of schizophrenia and bipolar disorder, including the management of acute mania and maintenance treatment. It is also used as an adjunctive treatment for major depressive disorder. Notable side effects include significant weight gain, metabolic abnormalities (hyperglycaemia, dyslipidaemia), sedation, and anticholinergic effects. It has a higher risk of stroke in elderly patients with dementia, so it is not recommended in this population. Dose adjustments may be needed in patients with hepatic impairment or with interacting drugs. Monitor weight, blood glucose, and lipid profile regularly.
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BNF; local formulary