Zyprexa (Olanzapine) Dose Escalation
Dose adjustments for olanzapine should occur at intervals of not less than 1 week, as steady-state plasma concentrations are not achieved until approximately one week in typical patients. 1
Standard Dose Escalation Protocol
Adults with Schizophrenia
- Starting dose: 5-10 mg once daily 1
- Target dose: 10 mg/day, achieved within several days 1
- Escalation interval: Wait at least 1 week between dose adjustments due to the time required to reach steady-state 1
- Increment size: 5 mg increases when adjustments are necessary 1
- Maximum dose: 20 mg/day (doses above this are not indicated) 1
Critical consideration: Doses above 10 mg/day were not demonstrated to be more efficacious than 10 mg/day in clinical trials, so increases beyond the target dose should only occur after careful clinical assessment 1
Adolescents with Schizophrenia
- Starting dose: 2.5-5 mg once daily 1
- Target dose: 10 mg/day 1
- Increment size: 2.5-5 mg when adjustments are needed 1
- Maximum studied dose: 20 mg/day (safety and effectiveness above this have not been evaluated) 1
Special Populations Requiring Slower Titration
The following patients should start at 5 mg and have dose escalation performed with caution: 1
- Debilitated patients
- Patients with predisposition to hypotensive reactions
- Nonsmoking female patients ≥65 years of age
- Patients who may be more pharmacodynamically sensitive to olanzapine
- Patients with hepatic impairment 2
For these populations, consider smaller dose increments of 2.5 mg rather than 5 mg. 2
Pharmacokinetic Rationale
The one-week minimum interval is based on olanzapine's pharmacokinetic profile: 3
- Half-life: 21-54 hours (mean 33 hours) in healthy individuals 3
- Time to steady-state: Approximately 1 week 1
- Clearance variability: 4-fold range among individuals, influenced by gender, smoking status, and age 3
Factors Affecting Metabolism
Faster metabolism (may require higher doses or more frequent adjustments): 3
- Male gender
- Smoking status (tobacco induces CYP1A2)
- Concurrent carbamazepine use
Slower metabolism (requires more cautious escalation): 3
- Female gender
- Nonsmoking status
- Elderly age
- Concurrent fluvoxamine use (CYP1A2 inhibitor increases olanzapine concentrations)
Common Pitfalls to Avoid
- Do not increase doses more frequently than weekly - premature dose escalation before steady-state is reached can lead to accumulation and increased adverse effects 1
- Do not routinely exceed 10 mg/day without documented inadequate response - higher doses showed no additional efficacy in trials 1
- Do not use standard escalation schedules in elderly, debilitated, or female nonsmokers - these populations require lower starting doses and slower titration 1
Monitoring During Dose Escalation
Reassess patients after each dose increase for: 2
- Changes in psychotic symptoms (positive and negative)
- Functional improvement
- Adverse effects (weight gain, somnolence, metabolic changes)
- Risk factors for complications