Atypical antipsychotic – thienobenzodiazepine
ATC code: N05AH03 (Olanzapine)
An antagonist at dopamine D1, D2, D4, serotonin 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, muscarinic M1–M5, histamine H1, and α1-adrenoceptors. The broad receptor profile drives strong antipsychotic effect but also high metabolic disturbance and weight gain rates (among the highest in atypical antipsychotics). The Huhn 2019 network meta-analysis showed one of the highest efficacies. CYP1A2-metabolized.
First line
First-line in acute mania and maintenance of bipolar I disorder per CANMAT 2018. Dose 10–20 mg daily. Combined with fluoxetine (Symbyax), -approved for bipolar depression and treatment-resistant depression.
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First line
First-line for schizophrenia and schizoaffective disorder per 2020 and NG178 (2020). Starting dose 5–10 mg once daily at bedtime, titrated to 10–20 mg. Among the most effective atypical antipsychotics (Huhn 2019), but choice is individualized due to metabolic adverse effects. In patients at metabolic syndrome risk, aripiprazole is preferred.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Off-label low-dose olanzapine (2.5–5 mg at bedtime) for insomnia is common due to marked sedation via H1 blockade. 2017 does not recommend this use – evidence is absent, and the risk of metabolic disturbance, 5–10 kg weight gain over 6 months, type 2 diabetes, and tardive dyskinesia with prolonged use is not justified by the symptomatic effect. First-line for chronic insomnia is cognitive-behavioral therapy for insomnia (CBT-I). When pharmacotherapy is needed, melatonin or a sedating antidepressant are preferred.
Off-label use, common in Spain, Russia, and Latin America.
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Boxed warning
FDA boxed warning: increased mortality in elderly patients with dementia on atypical antipsychotics. The Zyprexa Relprevv long-acting form carries post-injection delirium/sedation syndrome (PDSS) risk.
T3 use carries neonatal extrapyramidal and withdrawal risk. In pregnant psychotic patients, decisions are made with the psychiatrist.
Milk concentrations are low. Use during lactation cautiously with monitoring of infant sedation and weight gain.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Olanzapine is evaluated for the following indications with varying evidence strength: Schizophrenia (evidence tier A), Bipolar disorder maintenance (evidence tier A), Chronic insomnia in adults under 55 (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Olanzapine (≥ 1 in 100): Weight gain (often 5–10 kg over 6 months), Drowsiness and sedation, Hyperlipidemia, hyperglycemia, Dry mouth, Constipation, Orthostatic hypotension. See the Safety section for uncommon and serious reactions.
FDA category C. T3 use carries neonatal extrapyramidal and withdrawal risk. In pregnant psychotic patients, decisions are made with the psychiatrist.
Milk concentrations are low. Use during lactation cautiously with monitoring of infant sedation and weight gain.
Olanzapine is contraindicated in: Olanzapine hypersensitivity; Angle-closure glaucoma; Dementia in older adults; Parkinson's disease, Lewy body dementia; Pregnancy (except life-saving indications). Full list in the Safety section.
FDA boxed warning: increased mortality in elderly patients with dementia on atypical antipsychotics. The Zyprexa Relprevv long-acting form carries post-injection delirium/sedation syndrome (PDSS) risk.