What is Zyprexa (Olanzapine) Used For?
Zyprexa (olanzapine) is FDA-approved for treating schizophrenia, acute manic or mixed episodes of bipolar I disorder, maintenance treatment of bipolar I disorder, acute agitation in schizophrenia and bipolar mania, and as combination therapy with fluoxetine for bipolar depression and treatment-resistant depression. 1
Primary FDA-Approved Indications
Schizophrenia
- Adults: Olanzapine is approved for treatment of schizophrenia with efficacy established in two 6-week trials and one maintenance trial, typically started at 5-10 mg once daily with a target of 10 mg/day 1
- Adolescents (ages 13-17): Approved for schizophrenia with efficacy established in one 6-week trial, started at 2.5-5 mg once daily with a target of 10 mg/day, though the increased potential for weight gain and dyslipidemia may lead clinicians to consider other drugs first 1
Bipolar I Disorder
- Acute manic or mixed episodes in adults: Efficacy established in two 3- to 4-week trials and one maintenance trial, with starting dose of 10-15 mg once daily 1
- Acute manic or mixed episodes in adolescents (ages 13-17): Started at 2.5-5 mg once daily with target of 10 mg/day 1
- Maintenance treatment: Olanzapine is approved for preventing relapse in bipolar I disorder and is currently the only atypical antipsychotic with this specific FDA approval 2
- Adjunctive therapy: Approved as adjunct to valproate or lithium for manic or mixed episodes, with efficacy established in two 6-week trials in adults 1
Acute Agitation
- Intramuscular formulation: Approved for treatment of acute agitation associated with schizophrenia and bipolar I mania, with efficacy established in three 1-day trials using 10 mg IM (or 5-7.5 mg when clinically warranted) 1
Combination Therapy with Fluoxetine
- Bipolar depression: Approved in combination with fluoxetine for treatment of depressive episodes associated with bipolar I disorder 1
- Treatment-resistant depression: Approved in combination with fluoxetine (as Symbyax) for adults with treatment-resistant depression 1
Additional Clinical Uses (Supported by Guidelines)
Chemotherapy-Induced Nausea and Vomiting
- The NCCN recommends olanzapine as a category 1 first-line option for CINV as part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy, with significant increases in complete response rates compared to placebo 3
PTSD-Related Nightmares
- Olanzapine may be considered for treatment of PTSD-associated nightmares, though evidence is limited to small uncontrolled case series showing rapid improvement in combat-related PTSD resistant to SSRIs and benzodiazepines 3
Comparative Efficacy Evidence
Versus Conventional Antipsychotics
- Olanzapine 5-20 mg/day demonstrated significantly superior efficacy to haloperidol 5-20 mg/day in overall psychopathology improvements, treatment of depressive and negative symptoms, with comparable effects on positive symptoms and significantly lower 1-year relapse risk 4
Versus Other Mood Stabilizers
- In acute mania, olanzapine showed equal or superior efficacy to valproate and superior efficacy when combined with lithium or valproate compared to mood stabilizer monotherapy 5
- For maintenance therapy, olanzapine demonstrated superior efficacy to placebo in preventing manic and depressive relapses and was non-inferior to lithium or valproate 5
Critical Safety Considerations
Boxed Warning
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death; olanzapine is not approved for treatment of dementia-related psychosis 1
Metabolic Side Effects
- Olanzapine is associated with substantial weight gain and metabolic syndrome, warranting clinician vigilance particularly in adolescents where the increased potential for weight gain and dyslipidemia may lead to considering other drugs first 1, 5, 6
- Studies in adolescents demonstrated significant weight gain and metabolic measures, leading to recommendations for olanzapine as a second-line medication when other atypicals are available 6
Monitoring Requirements
- The American Academy of Child and Adolescent Psychiatry recommends monitoring body mass index monthly for 3 months then quarterly, and blood pressure, fasting glucose, and lipids after 3 months then yearly for patients on atypical antipsychotics including olanzapine 7
Important Clinical Caveats
Pediatric Use Considerations
- Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after thorough diagnostic evaluation and with careful consideration of potential risks 1
- Safety and effectiveness in patients under 13 years of age have not been established 1
Drug Interactions
- Olanzapine should be used with caution when concurrently used with metoclopramide, phenothiazines, or haloperidol due to risk of excessive dopamine blockade 3
- Patients should avoid alcohol while taking olanzapine 1