Zyprexa (Olanzapine) Uptitration Protocol
For adults with schizophrenia, start olanzapine at 5-10 mg once daily and reach the target dose of 10 mg/day within several days, with any further dose adjustments occurring at intervals of at least 1 week using 5 mg increments. 1
Standard Adult Dosing for Schizophrenia
- Initial dose: 5-10 mg once daily, taken without regard to meals 1
- Target dose: 10 mg/day, achieved within several days of initiation 1
- Titration interval: Wait at least 1 week between dose adjustments, as steady-state concentrations require approximately 1 week to achieve 1
- Dose increments: Use 5 mg increases when uptitrating 1
- Maximum dose: 20 mg/day (doses above this are not indicated) 1
Important Caveat on Dose Escalation
Doses above 10 mg/day should only be used after clinical assessment, as trials showed no additional efficacy benefit beyond 10 mg/day despite demonstrating efficacy in the 10-15 mg/day range. 1 This means the 10 mg target is typically sufficient for most patients.
Bipolar I Disorder (Manic or Mixed Episodes)
- Initial dose: 10-15 mg once daily 1
- Titration interval: Wait at least 24 hours between dose adjustments 1
- Dose increments: Use 5 mg increases when uptitrating 1
- Effective range: 5-20 mg/day demonstrated antimanic efficacy 1
Special Populations Requiring Lower Starting Doses
Start at 5 mg once daily in the following patients: 1
- Debilitated patients
- Patients with predisposition to hypotensive reactions
- Nonsmoking female patients ≥65 years of age
- Patients with hepatic impairment 2, 3
- Patients who may be more pharmacodynamically sensitive to olanzapine
When dose escalation is indicated in these populations, proceed with caution. 1
Adolescent Dosing (Ages 13-17)
- Initial dose: 2.5-5 mg once daily 1
- Target dose: 10 mg/day 1
- Dose increments: Use 2.5-5 mg increases when uptitrating 1
- Effective range: Clinical trials demonstrated efficacy with 2.5-20 mg/day (mean modal dose 12.5 mg/day for schizophrenia, 10.7 mg/day for bipolar disorder) 1
- Maximum studied dose: 20 mg/day (safety and effectiveness above this not established) 1
Delirium Management in Palliative Care
- Initial dose: 2.5-5 mg orally or subcutaneously as needed 2
- Dose range: 2.5-15 mg daily for ongoing management 4
- Special consideration: Use lower doses in older patients and those with hepatic impairment 2
Critical Safety Monitoring During Uptitration
Monitor for these common side effects, especially during initial titration: 2, 3
- Drowsiness and sedation
- Orthostatic hypotension (particularly concerning during initial dose escalation)
- Metabolic effects with long-term use
Dangerous Drug Interaction
Exercise extreme caution when combining olanzapine with benzodiazepines—this combination increases risk of oversedation, respiratory depression, and fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine. 2, 3
Maintenance Treatment Considerations
- Schizophrenia maintenance: 10-20 mg/day has demonstrated effectiveness in preventing relapse 1
- Bipolar maintenance: 5-20 mg/day after achieving responder status for approximately 2 weeks 1
- Long-term strategy: Use the lowest dose needed to maintain remission and periodically reassess the need for continued treatment 1
Common Pitfall to Avoid
Do not rush dose escalation beyond 10 mg/day in schizophrenia patients, as higher doses were not more effective than 10 mg/day in clinical trials, yet increase the risk of side effects. 1 Only increase above 10 mg/day after thorough clinical assessment indicates it is necessary.