What is Zyprexa (olanzapine) used for?

Zyprexa (Olanzapine): Uses and Clinical Applications

Zyprexa (olanzapine) is an atypical antipsychotic medication primarily indicated for the treatment of schizophrenia and bipolar I disorder in both adults and adolescents, with additional uses including management of chemotherapy-induced nausea and vomiting, and treatment of PTSD-related nightmares. 1

FDA-Approved Indications

• Treatment of schizophrenia in adults and adolescents (ages 13-17) 1
• Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and adolescents (ages 13-17) 1
• Maintenance treatment of bipolar I disorder in adults 1
• Adjunctive therapy with lithium or valproate for treatment of manic or mixed episodes associated with bipolar I disorder in adults 1
• Treatment of acute agitation associated with schizophrenia and bipolar I mania (intramuscular formulation) 1
• Treatment of depressive episodes associated with bipolar I disorder (in combination with fluoxetine) 1
• Treatment of treatment-resistant depression (in combination with fluoxetine) 1

Dosing Considerations

• Schizophrenia in adults: Start at 5-10 mg once daily; target 10 mg/day within several days 1
• Schizophrenia in adolescents: Start at 2.5-5 mg once daily; target 10 mg/day 1
• Bipolar I disorder (manic or mixed episodes) in adults: Start at 10 or 15 mg once daily 1
• Bipolar I disorder (manic or mixed episodes) in adolescents: Start at 2.5-5 mg once daily; target 10 mg/day 1
• Bipolar I disorder with lithium or valproate in adults: Start at 10 mg once daily 1

Efficacy in Bipolar Disorder

• Olanzapine is effective for acute mania, demonstrating superior efficacy to placebo and equal or superior efficacy to valproate 2
• Combination therapy with lithium or valproate shows superior efficacy compared to mood stabilizer monotherapy for acute mania 2
• Maintenance trials demonstrate olanzapine is more effective than placebo in preventing both manic and depressive relapses 2
• Olanzapine is non-inferior to lithium or valproate for maintenance treatment 2

Efficacy in Schizophrenia

• Olanzapine demonstrates rapid onset of action (within 1-2 weeks) in schizophrenia treatment 3
• Clinical benefits are maintained for treatment periods up to 1 year, with decreased probability of hospitalization compared to haloperidol 3
• Olanzapine improves negative symptoms to a greater extent than haloperidol in some comparative trials 3

Off-Label Uses

Chemotherapy-Induced Nausea and Vomiting (CINV)

• Olanzapine is effective as part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy 4
• When combined with aprepitant/fosaprepitant, a 5-HT3 antagonist, and dexamethasone, olanzapine significantly increases complete response rates compared to placebo 4
• Recommended as a category 1 first-line option for CINV by the NCCN 4

PTSD-Related Nightmares

• May be considered for treatment of PTSD-associated nightmares, though evidence is limited 4
• In a small uncontrolled case series, 10-20 mg olanzapine added to current psychotropic treatment showed rapid improvement in combat-related PTSD resistant to SSRIs and benzodiazepines 4

Safety Considerations

Important Warnings

• Boxed warning: Increased mortality in elderly patients with dementia-related psychosis 1
• Should be used with caution in elderly patients due to risk of death in patients with dementia-related psychosis 4

Common Side Effects

• Weight gain and metabolic syndrome are significant concerns 5, 2
• Fatigue, drowsiness, and sleep disturbances 4
• Dry mouth and increased appetite 3

Special Populations

• Adolescents have increased potential for weight gain and dyslipidemia compared to adults, which may lead clinicians to consider prescribing other drugs first 1, 5
• A 5-mg dose may be considered in elderly or oversedated patients 4

Drug Interactions

• Caution when using olanzapine concurrently with metoclopramide, phenothiazines, or haloperidol due to risk of excessive dopamine blockade 4
• Rare but serious skin reaction (DRESS syndrome) has been reported 4

Clinical Decision Making

• For bipolar disorder treatment, selection should be based on: evidence of efficacy, phase of illness, presence of confounding presentations, side effect profile, patient's history of medication response, and patient/family preferences 4
• For adolescents, olanzapine is often recommended as a second-use medication due to equivalent efficacy to other atypical antipsychotics but with more significant metabolic side effects 5
• When treating acute mania in bipolar I disorder, olanzapine is considered standard therapy along with lithium and valproate 4