What are the indications for olanzapine (atypical antipsychotic) in adults and adolescents with various psychiatric conditions, including schizophrenia and bipolar disorder?

Indications for Olanzapine

Olanzapine is FDA-approved for schizophrenia (adults and adolescents 13-17 years), acute treatment of manic or mixed episodes in bipolar I disorder (adults and adolescents 13-17 years), maintenance treatment of bipolar I disorder, adjunctive treatment with lithium or valproate for bipolar mania, acute agitation in schizophrenia and bipolar I mania (intramuscular formulation), and in combination with fluoxetine for bipolar depression and treatment-resistant depression. 1

FDA-Approved Indications in Adults

Schizophrenia

• Olanzapine is indicated for treatment of schizophrenia in adults, with efficacy established in two 6-week trials and one maintenance trial 1
• Oral dosing starts at 5-10 mg once daily, with a target of 10 mg/day within several days 1
• Olanzapine demonstrates superior efficacy compared to haloperidol in overall psychopathology improvements, treatment of depressive and negative symptoms, with comparable effects on positive psychotic symptoms 2

Bipolar I Disorder - Acute Mania/Mixed Episodes

• Olanzapine is approved for acute treatment of manic or mixed episodes associated with bipolar I disorder, with efficacy established in two 3-4 week trials and one maintenance trial 1
• The American Academy of Child and Adolescent Psychiatry recommends olanzapine as a first-line atypical antipsychotic for acute mania/mixed episodes 3
• Oral dosing starts at 10-15 mg once daily in adults 1
• Olanzapine 10-20 mg/day combined with lithium or valproate demonstrates superior efficacy to mood stabilizers alone for acute mania 3

Bipolar I Disorder - Maintenance Treatment

• Olanzapine is indicated for maintenance treatment of bipolar I disorder, demonstrating superior efficacy to placebo in preventing manic and depressive relapses 4
• Olanzapine shows non-inferior efficacy compared to lithium or valproate for maintenance therapy 4

Bipolar I Disorder - Adjunctive Treatment

• Olanzapine is approved as adjunct to valproate or lithium for treatment of manic or mixed episodes, with efficacy established in two 6-week trials 1
• The American Academy of Child and Adolescent Psychiatry recommends starting at 10 mg once daily when used adjunctively 3
• Combination therapy with olanzapine plus lithium or valproate is more effective than valproate alone for acute mania 3

Acute Agitation (Intramuscular Formulation)

• Olanzapine intramuscular is indicated for acute agitation associated with schizophrenia and bipolar I mania, with efficacy established in three 1-day trials 1
• Dosing is 10 mg IM (5 mg or 7.5 mg when clinically warranted), with assessment for orthostatic hypotension prior to subsequent dosing, maximum 3 doses 2-4 hours apart 1

Bipolar Depression (Combination with Fluoxetine)

• Olanzapine in combination with fluoxetine is indicated for depressive episodes associated with bipolar I disorder 1
• The American Academy of Child and Adolescent Psychiatry recommends olanzapine-fluoxetine combination as a first-line option for bipolar depression 3
• Starting dose is 5 mg olanzapine with 20 mg fluoxetine once daily in adults 1
• Olanzapine monotherapy is not indicated for treatment of bipolar depression 1

Treatment-Resistant Depression (Combination with Fluoxetine)

• Olanzapine combined with fluoxetine is indicated for treatment-resistant depression in adults 1
• Starting dose is 5 mg olanzapine with 20 mg fluoxetine once daily 1
• Safety of co-administration above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated 1

FDA-Approved Indications in Adolescents (Ages 13-17)

Schizophrenia in Adolescents

• Olanzapine is approved for schizophrenia in adolescents aged 13-17 years, with efficacy established in one 6-week trial 1
• Starting dose is 2.5-5 mg once daily, with target of 10 mg/day 1
• The increased potential for weight gain and dyslipidemia in adolescents compared with adults may lead clinicians to consider prescribing other drugs first 1
• Olanzapine demonstrated significantly greater reduction in Brief Psychiatric Rating Scale for Children (BPRS-C) total score compared to placebo at 6 weeks 5

Bipolar I Disorder in Adolescents

• Olanzapine is approved for acute treatment of manic or mixed episodes in adolescents aged 13-17 years, with efficacy established in one 3-week trial 1
• Starting dose is 2.5-5 mg once daily, with target of 10 mg/day 1
• Mean reduction in Adolescent Structured Young Mania Rating Scale (YMRS) total score was significantly greater with olanzapine than placebo at 3 weeks 5
• The increased potential for weight gain and dyslipidemia in adolescents compared with adults may lead clinicians to consider prescribing other drugs first 1

Bipolar Depression in Adolescents (Combination with Fluoxetine)

• Olanzapine combined with fluoxetine is indicated for depressive episodes associated with bipolar I disorder in children and adolescents 1
• Starting dose is 2.5 mg olanzapine with 20 mg fluoxetine once daily 1
• Safety of co-administration above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10-17 1

Important Clinical Considerations for Pediatric Use

• 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
• Olanzapine-treated adolescents experience greater increases in bodyweight, sedation, blood lipids, serum prolactin, and liver transaminase levels compared to olanzapine-treated adults 5
• Sedation and weight gain are the most common adverse events in placebo-controlled trials in adolescents 5
• Extrapyramidal symptoms occurred in 10% of olanzapine recipients compared with 6% of placebo recipients in adolescent trials 5
• Due to metabolic side-effects, olanzapine is often recommended as a second-line medication in adolescents 6, 7

Critical Safety Warnings

Boxed Warning

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death 1
• Olanzapine is not approved for treatment of patients with dementia-related psychosis 1
• Increased incidence of cerebrovascular adverse events (stroke, transient ischemic attack) in elderly patients with dementia-related psychosis 1

Metabolic Monitoring Requirements

• The American Diabetes Association recommends intensive metabolic monitoring for adolescents prescribed olanzapine, including baseline and follow-up measurements of BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel 8
• The American Academy of Child and Adolescent Psychiatry advises monitoring BMI monthly for 3 months then quarterly, and blood pressure, fasting glucose, and lipids after 3 months then yearly 3

Common Pitfalls to Avoid

• Never use olanzapine as first-line treatment for eating disorder anxiety instead of evidence-based psychotherapy 8
• Avoid prescribing olanzapine without intensive metabolic monitoring, particularly in populations already at metabolic risk 8
• Do not use olanzapine monotherapy for bipolar depression—it must be combined with fluoxetine for this indication 1
• Inadequate duration of maintenance therapy leads to high relapse rates; continue for at least 12-24 months after stabilization 3
• Failure to monitor for metabolic side effects, particularly weight gain and dyslipidemia, is a significant concern especially in adolescents 3, 5