What are the indications, recommended dosing regimens, formulations, contraindications, common adverse effects, and monitoring requirements for Zyprexa (olanzapine) in adults with schizophrenia or bipolar I disorder and in adolescents aged 10‑17 with bipolar I mania?

Zyprexa (Olanzapine): Clinical Overview

FDA-Approved Indications

Zyprexa is FDA-approved for multiple psychiatric conditions across different age groups, with specific dosing requirements for each population. 1

Adults

• Schizophrenia (oral formulation) 1
• Acute treatment of manic or mixed episodes associated with bipolar I disorder (oral formulation) 1
• Maintenance treatment of bipolar I disorder (oral formulation) 1
• Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder 1
• Acute agitation associated with schizophrenia and bipolar I mania (intramuscular formulation) 1
• Depressive episodes associated with bipolar I disorder (in combination with fluoxetine) 1
• Treatment-resistant depression (in combination with fluoxetine) 1

Adolescents (Ages 13–17)

• Schizophrenia (oral formulation) 1
• Acute treatment of manic or mixed episodes associated with bipolar I disorder (oral formulation) 1

Children and Adolescents (Ages 10–17)

• Depressive episodes associated with bipolar I disorder (in combination with fluoxetine) 1

The increased potential for weight gain and dyslipidemia in adolescents compared with adults may lead clinicians to consider prescribing other drugs first in this population. 1

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Dosing Regimens

Schizophrenia

Adults

• Starting dose: 5–10 mg once daily 1
• Target dose: 10 mg/day within several days 1
• Therapeutic range: 5–20 mg/day 2

Adolescents (Ages 13–17)

• Starting dose: 2.5–5 mg once daily 1
• Target dose: 10 mg/day 1

Bipolar I Disorder (Manic or Mixed Episodes)

Adults (Monotherapy)

• Starting dose: 10 or 15 mg once daily 1
• Therapeutic range: 10–20 mg/day 2

Adults (Adjunct to Lithium or Valproate)

• Starting dose: 10 mg once daily 1

Adolescents (Ages 13–17)

• Starting dose: 2.5–5 mg once daily 1
• Target dose: 10 mg/day 1

Acute Agitation (Schizophrenia and Bipolar I Mania)

Adults (Intramuscular)

• Standard dose: 10 mg IM 1
• Lower dose when clinically warranted: 5 mg or 7.5 mg IM 1
• Maximum: 3 doses given 2–4 hours apart 1
• Assess for orthostatic hypotension prior to subsequent dosing 1

Bipolar Depression (in Combination with Fluoxetine)

Adults

• Starting dose: 5 mg olanzapine + 20 mg fluoxetine once daily 1
• Maximum evaluated dose: 18 mg olanzapine + 75 mg fluoxetine 1

Children and Adolescents (Ages 10–17)

• Starting dose: 2.5 mg olanzapine + 20 mg fluoxetine once daily 1
• Maximum evaluated dose: 12 mg olanzapine + 50 mg fluoxetine 1

Treatment-Resistant Depression (in Combination with Fluoxetine)

Adults

• Starting dose: 5 mg olanzapine + 20 mg fluoxetine once daily 1
• Maximum evaluated dose: 18 mg olanzapine + 75 mg fluoxetine 1

Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder or treatment-resistant depression. 1

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Formulations

• Tablets (not scored): 2.5,7.5,10,15,20 mg 1
• Orally Disintegrating Tablets (not scored): 5,10,15,20 mg 1
• Intramuscular Injection: 10 mg single-dose vial 1

Olanzapine may be given without regard to meals. 1

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Contraindications

There are no contraindications with Zyprexa monotherapy. 1

When using Zyprexa in combination with fluoxetine, refer to the Contraindications section of the package insert for Symbyax. 1

When using Zyprexa in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products. 1

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Common Adverse Effects

Most Frequent Adverse Events in Adolescents

• Sedation (most common) 3
• Weight gain (most common) 3
• Extrapyramidal symptoms (10% in olanzapine recipients vs. 6% in placebo recipients) 3

Metabolic Effects in Adolescents vs. Adults

Olanzapine-treated adolescents are likely to experience greater increases in bodyweight, sedation, blood lipids, serum prolactin, and liver transaminase levels than olanzapine-treated adults. 3

Weight Gain

Olanzapine is associated with a higher incidence of weight gain than most atypical agents. 4, 5

Extrapyramidal Symptoms

Olanzapine has a low incidence of extrapyramidal symptoms. 4, 5

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Boxed Warning

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 1

Zyprexa is not approved for the treatment of patients with dementia-related psychosis. 1

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Warnings and Precautions

Elderly Patients with Dementia-Related Psychosis

Increased risk of death and increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack). 1

Suicide Risk

The possibility of a suicide attempt is inherent in schizophrenia and in bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy. 1

When using in combination with fluoxetine, also refer to the Boxed Warning and Warnings and Precautions sections of the package insert for Symbyax. 1

Neuroleptic Malignant Syndrome

Manage with immediate discontinuation and close monitoring. 1

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Discontinue if DRESS is suspected. 1

Metabolic Changes

Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. 1

Tardive Dyskinesia

Risk of tardive dyskinesia exists with long-term use. 1

Anticholinergic (Antimuscarinic) Effects

Olanzapine may cause anticholinergic effects. 1

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Monitoring Requirements

Baseline Assessment (Before Initiating Olanzapine)

• Body mass index (BMI) 2
• Waist circumference 2
• Blood pressure 2
• Fasting glucose 2
• Fasting lipid panel 2

Follow-Up Monitoring

First 6 Weeks

• BMI and waist circumference: Weekly 2
• Blood pressure: Weekly 2
• Fasting glucose: Repeat at week 4 2

At 3 Months

• Repeat all baseline measures (BMI, waist circumference, blood pressure, fasting glucose, fasting lipid panel) 2

Ongoing (After 3 Months)

• BMI: Quarterly 2
• Blood pressure, fasting glucose, and fasting lipid panel: Annually 2

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Special Populations

Adolescents

Careful consideration of risk-benefit is recommended before using olanzapine in adolescents due to greater increases in bodyweight, sedation, blood lipids, serum prolactin, and liver transaminase levels compared with adults. 3

Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after a thorough diagnostic evaluation and with careful consideration of the potential risks. 1

Debilitated or Pharmacodynamically Sensitive Patients

Lower starting dose recommended in debilitated or pharmacodynamically sensitive patients, or patients with predisposition to hypotensive reactions, or with potential for slowed metabolism. 1

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Efficacy Evidence

Schizophrenia in Adolescents

In a randomized, double-blind, multicentre, 6-week trial in adolescents aged 13–17 years with schizophrenia, the least squares mean reduction from baseline to 6 weeks in the Brief Psychiatric Rating Scale for Children (BPRS-C) total score was significantly greater with olanzapine than with placebo. 3

Bipolar I Disorder (Manic or Mixed Episodes) in Adolescents

In a randomized, double-blind, multicentre, 3-week trial in adolescents aged 13–17 years with manic or mixed episodes associated with bipolar I disorder, the mean reduction from baseline to 3 weeks in the Adolescent Structured Young Mania Rating Scale (YMRS) total score was significantly greater with olanzapine than with placebo. 3

Maintenance Therapy in Bipolar I Disorder

Olanzapine is effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders, and is currently the only atypical antipsychotic approved for this indication. 4, 5

Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. 4, 5

Acute Mania in Adults

In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol, and risperidone in reducing the symptoms of mania and inducing remission. 4, 5

Olanzapine in combination with lithium or valproate is more effective than monotherapy with mood stabilizers for acute mania in bipolar disorder. 2

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Common Pitfalls to Avoid

Underdosing

Underdosing olanzapine can delay therapeutic response; an adequate trial requires 4–6 weeks at therapeutic doses before concluding ineffectiveness. 2

Premature Discontinuation

Premature discontinuation can lead to inadequate trial and high relapse rates. 2

Inadequate Metabolic Monitoring

Failure to monitor for metabolic side effects of medications, particularly atypical antipsychotics, is a common pitfall. 2

Excessive Polypharmacy

Excessive polypharmacy should be avoided; olanzapine monotherapy is effective for acute psychosis. 2

Combining with High-Dose Benzodiazepines

Avoid combining olanzapine with benzodiazepines at high doses, as fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine. 2

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Clinical Considerations

Olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive, or mixed episodes associated with bipolar I disorder. 4, 5

Safety and tolerability concerns with olanzapine include weight gain and metabolic syndrome, which warrant clinician vigilance and discernment. 6

Maintenance therapy should continue for at least 12–24 months after mood stabilization, with some patients requiring lifelong treatment. 2