What are the indications for Zyprexa (olanzapine)?

Indications for Zyprexa (Olanzapine)

Zyprexa (olanzapine) is FDA-approved for the treatment of schizophrenia in adults and adolescents (ages 13-17), acute manic or mixed episodes associated with bipolar I disorder as monotherapy or as adjunct to lithium/valproate in adults and adolescents (ages 13-17), and maintenance treatment of bipolar I disorder in adults. 1

Primary Indications

Schizophrenia

• Approved for adults and adolescents (ages 13-17) 1
• Efficacy established in three clinical trials in adults: two 6-week trials and one maintenance trial 1
• Efficacy in adolescents established in one 6-week trial 1, 2
• Superior antipsychotic efficacy compared to haloperidol in acute phase schizophrenia 3
• Effective for both positive and negative symptoms of schizophrenia 3

Bipolar I Disorder

• Approved for acute treatment of manic or mixed episodes in adults and adolescents (ages 13-17) 1
• Approved for maintenance treatment of bipolar I disorder in adults 1, 4
• Efficacy established in three clinical trials in adults with manic or mixed episodes: two 3-4 week trials and one maintenance trial 1
• Efficacy in adolescents established in one 3-week trial 1, 2
• Superior to placebo and equal or superior to valproate in acute mania trials 5, 6
• More effective than lithium or valproate monotherapy when used in combination for acute mania 5, 6
• Currently the only atypical antipsychotic approved for maintenance therapy to prevent recurrence in responders 4

Adjunctive Therapy

• Approved as adjunct to lithium or valproate for treatment of manic or mixed episodes in bipolar I disorder 1
• Efficacy established in two 6-week clinical trials in adults 1
• Combination with lithium or valproate more efficacious than mood stabilizer monotherapy in preventing manic relapse 5, 6

Other FDA-Approved Indications

• Treatment of acute agitation associated with schizophrenia and bipolar I mania (as ZYPREXA IntraMuscular) 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

Off-Label Uses

Delirium Management

• Used for treatment of delirium in cancer patients at doses of 2.5-5 mg PO or SC 7
• May cause drowsiness and orthostatic hypotension 7
• Caution advised when combining with benzodiazepines due to risk of oversedation and respiratory depression 7

Antiemetic Therapy

• Used as part of a 4-drug regimen for chemotherapy-induced nausea and vomiting (CINV) 7
• Recommended as part of a regimen with aprepitant/fosaprepitant, 5-HT3 antagonist, and dexamethasone for highly emetogenic chemotherapy 7
• Shown to increase complete response rates compared to placebo in preventing CINV 7

Special Considerations

Adolescent Treatment

• Clinicians should consider the increased potential for weight gain and dyslipidemia in adolescents compared to adults 1
• Medication therapy for pediatric schizophrenia and bipolar I disorder should be initiated only after thorough diagnostic evaluation 1
• Adolescents may experience greater increases in body weight, sedation, blood lipids, serum prolactin, and liver transaminase levels than adults 2

Safety Concerns

• Common side effects include weight gain, somnolence, dizziness, and anticholinergic effects 3
• Metabolic effects are a significant concern, particularly with long-term use 7, 5
• Should be used with caution in elderly patients due to increased risk of cerebrovascular events and mortality in dementia-related psychosis 7
• Caution advised when using olanzapine concurrently with metoclopramide, phenothiazines, or haloperidol due to risk of excessive dopamine blockade 7

Dosing Considerations

• For schizophrenia in adults: typically 5-20 mg/day 3
• For bipolar mania in adults: typically 5-20 mg/day 6
• For adolescents: lower starting doses recommended 1
• For delirium: 2.5-5 mg PO or SC, with reduced doses in older patients and those with hepatic impairment 7

Olanzapine has demonstrated efficacy across multiple psychiatric conditions, with particular strength in treating both the manic and maintenance phases of bipolar disorder, as well as the positive and negative symptoms of schizophrenia. However, metabolic side effects require careful monitoring and consideration of risk-benefit ratio, especially in adolescent populations.