What is the indication for Zyprexa (olanzapine)?

Indications for Zyprexa (Olanzapine)

Zyprexa (olanzapine) is primarily indicated for the treatment of schizophrenia, bipolar I disorder (both acute manic/mixed episodes and maintenance treatment), and acute agitation associated with these conditions. 1

FDA-Approved Indications

Oral Formulation

1. Schizophrenia

   • Adults: Established in three clinical trials (two 6-week trials and one maintenance trial)
   • Adolescents (13-17 years): Established in one 6-week trial

2. Bipolar I Disorder

   • Acute treatment of manic or mixed episodes
     • Adults: Established in two 3-4 week trials
     • Adolescents (13-17 years): Established in one 3-week trial
   • Maintenance treatment of bipolar I disorder (adults)
   • Adjunct to valproate or lithium in treating manic/mixed episodes

3. In Combination with Fluoxetine

   • Treatment of depressive episodes associated with bipolar I disorder
   • Treatment-resistant depression

Intramuscular Formulation

• Treatment of acute agitation associated with schizophrenia and bipolar I mania

Efficacy in Different Populations

Schizophrenia

• Olanzapine has demonstrated superior efficacy to placebo in reducing symptoms of schizophrenia 2
• In adolescents, significant reductions in Brief Psychiatric Rating Scale for Children (BPRS-C) scores compared to placebo 3

Bipolar Disorder

• Acute Mania:

  • Superior to placebo and equal or superior to valproate 4, 5
  • Enhanced efficacy when combined with lithium or valproate compared to mood stabilizer monotherapy 5
  • Comparable efficacy to haloperidol 5

• Bipolar Depression:

  • Modest effect as monotherapy
  • Substantially enhanced effect when combined with fluoxetine 4, 5

• Maintenance Treatment:

  • More effective than placebo in preventing both manic and depressive relapses 4, 6
  • Non-inferior to lithium or valproate for relapse prevention 4
  • May be more effective than lithium specifically for preventing manic relapses 6

Acute Agitation

• Intramuscular olanzapine is at least as effective as intramuscular haloperidol or lorazepam for acute agitation associated with schizophrenia or bipolar mania 7
• Faster onset of action compared to other agents 7
• Also used in delirium management in cancer patients 2

Important Safety Considerations

Metabolic Effects

• Significant risk of weight gain and metabolic syndrome 4, 5
• Adolescents may experience greater increases in weight, blood lipids, and liver transaminase levels than adults 3
• Regular monitoring of weight, BMI, blood pressure, glucose, and lipids is recommended 8

Other Side Effects

• Common side effects include sedation, drowsiness, and sleep disturbances 2
• Low incidence of extrapyramidal symptoms compared to conventional antipsychotics 6, 7
• May cause orthostatic hypotension 2

Special Populations

• Elderly patients: Use with caution due to increased risk of death in elderly patients with dementia-related psychosis (boxed warning) 2
• Adolescents: The increased potential for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first 1
• Cancer patients with delirium: Starting dose of 2.5-5 mg orally or subcutaneously, with caution when combining with benzodiazepines due to risk of oversedation and respiratory depression 2

Dosing Considerations

• For schizophrenia and bipolar disorder, dosing should be tailored to the individual patient
• For acute agitation, intramuscular formulation provides rapid onset of action
• In elderly or oversedated patients, a lower 5-mg dose may be considered 2
• Available in oral tablet, orally disintegrating tablet (ODT), and intramuscular formulations 2

Clinicians should carefully weigh the established efficacy of olanzapine against its potential metabolic and other adverse effects when selecting this medication for treatment.