Olanzapine (Zyprexa) Treatment for Schizophrenia and Bipolar Disorder
For patients with schizophrenia, olanzapine should be administered at 5-10 mg once daily initially, with a target dose of 10 mg/day, while patients with bipolar disorder should start with 10-15 mg once daily, with dosage adjustments based on clinical response and tolerability. 1
Dosing Guidelines for Schizophrenia
Initial Treatment
- Start with 5-10 mg once daily without regard to meals
- Target dose: 10 mg/day within several days
- Efficacy demonstrated in range of 10-15 mg/day, but doses above 10 mg/day not shown to be more efficacious than 10 mg/day 1
- Dosage adjustments should occur at intervals of at least 1 week (steady state achieved after approximately 1 week)
- Dose increments/decrements of 5 mg recommended when adjustments needed
Special Populations
- Starting dose of 5 mg recommended for:
- Debilitated patients
- Those with predisposition to hypotensive reactions
- Patients with factors that may result in slower metabolism (e.g., nonsmoking female patients ≥65 years of age)
- Patients who may be more pharmacodynamically sensitive to olanzapine 1
Maintenance Treatment
- Effectiveness of 10-20 mg/day demonstrated in maintaining treatment response in patients stable for approximately 8 weeks 1
- Periodic reevaluation of long-term usefulness recommended
Dosing Guidelines for Bipolar I Disorder (Manic or Mixed Episodes)
Monotherapy
- Start with 10-15 mg once daily without regard to meals
- Dosage adjustments at intervals of not less than 24 hours
- Dose increments/decrements of 5 mg recommended
- Antimanic efficacy demonstrated in dose range of 5-20 mg/day in clinical trials 1
- Safety of doses above 20 mg/day not evaluated
Adjunctive Treatment with Lithium or Valproate
- Start with 10 mg once daily without regard to meals
- Antimanic efficacy demonstrated in dose range of 5-20 mg/day 1
Maintenance Treatment
- Benefit of maintaining bipolar I patients on monotherapy at 5-20 mg/day demonstrated after achieving responder status for average of 2 weeks 1
- Periodic reevaluation of long-term usefulness recommended
Administration Options
- ZYPREXA ZYDIS (orally disintegrating tablets) available for patients with difficulty swallowing
- Tablet disintegrates rapidly in saliva and can be swallowed with or without liquid 1
- Intramuscular formulation available for acute agitation (10 mg recommended dose) 1
Side Effects and Monitoring
Common Side Effects
- Weight gain (most significant compared to other antipsychotics)
- Somnolence, dizziness
- Anticholinergic effects (constipation and dry mouth) 2
- Transient asymptomatic liver enzyme elevations
Metabolic Considerations
- Monitor for weight gain and metabolic effects
- Consider combination with samidorphan or concurrent metformin to mitigate weight gain 3
- Regular monitoring of weight, BMI, blood pressure, fasting glucose, and lipid panel recommended
Special Precautions
- Avoid combining with benzodiazepines due to risk of oversedation and respiratory depression 3
- Use with caution in elderly patients and those with hepatic impairment (reduced doses recommended) 3
Comparative Efficacy
- Superior to haloperidol in overall improvements in psychopathology and treatment of depressive and negative symptoms 2
- Comparable to haloperidol in effects on positive psychotic symptoms
- Lower 1-year risk of relapse (rehospitalization) compared to haloperidol 2
- Associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone 2
Treatment-Resistant Cases
- For patients not responding to standard doses, consider clozapine as per treatment guidelines 3
- Some case reports suggest high-dose olanzapine (up to 60 mg/day) may be effective in treatment-resistant cases, though this exceeds FDA-approved dosing 4, 5
- High-dose treatment should be approached with caution due to increased risk of side effects
Clinical Pearls
- Olanzapine reaches steady state in approximately 1 week, so avoid frequent dose adjustments before this time
- Maximum FDA-approved dose is 20 mg/day; exceeding this dose increases side effect risk without clear evidence of additional benefit for most patients
- Consider combination with mood stabilizers (lithium or valproate) in bipolar disorder for enhanced efficacy
- Weight gain is a significant concern with olanzapine; implement monitoring and management strategies from treatment initiation