Olanzapine
Zyprexa
Second-Generation AntipsychoticGeneric availableTDM data
The mechanism of action of olanzapine, in the listed indications is unclear. However, the efficacy of olanzapine in schizophrenia could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism.
Compare Olanzapine →FDA-Approved Indications
- Schizophrenia (adults; adolescents 13–17 years)
- Acute manic or mixed episodes in Bipolar I — mono or adjunct with lithium/valproate
- Bipolar I maintenance (adults)
- Treatment-resistant depression — combination with fluoxetine (adults)
- Acute agitation in schizophrenia/bipolar mania (IM, adults)
Common Off-Label Uses
- Anorexia nervosa
- Chemotherapy-induced nausea
- Delirium
- Agitation in dementia
- Treatment-resistant OCD (adjunct)
What Sets This Drug Apart
- Among the most effective SGAs for overall symptom reduction in NMA data, with very low EPS (akathisia and parkinsonism risk ratios ~1.0 vs placebo)
- Highest or co-highest weight gain among SGAs: ~22% exceed 7% gain at 6 weeks, rising to ~64% by 12 months per FDA label
- FDA-approved combination with fluoxetine (Symbyax) for bipolar depression and treatment-resistant unipolar depression
- CYP1A2 substrate — smokers often need 1.5-2x higher doses than non-smokers; dose adjustment required with smoking changes
- Sedation is early-onset (median ~4 days) but often self-limited: 50% resolve within 1 week, 75% within 1 month
- Higher-dose strategy (20-40 mg/day, plasma level target 125-200 ng/mL) shows benefit in TRS when clozapine is not feasible
- Available as long-acting injectable (olanzapine pamoate) requiring 3-hour post-injection observation for rare delirium/sedation syndrome (0.2%)
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated wi