Olanzapine Initiation and Titration
Start olanzapine at 5-10 mg orally once daily for most adults with schizophrenia, targeting 10 mg/day within several days, with dose adjustments at weekly intervals in 5 mg increments as needed. 1
Standard Adult Dosing Algorithm
Initial Dose Selection
- Begin with 5-10 mg once daily for typical adult patients with schizophrenia, administered without regard to meals 1
- Target dose of 10 mg/day should be reached within several days 1
- Doses above 10 mg/day were not demonstrated to be more efficacious than 10 mg/day in clinical trials, though the therapeutic range extends to 15 mg/day 1
Titration Schedule
- Wait at least 1 week between dose adjustments since steady-state concentrations require approximately one week to achieve 1
- Use 5 mg increments or decrements when adjusting doses 1
- Maximum recommended dose is 20 mg/day; olanzapine is not indicated above this dose 1
Special Population Dosing
Reduced Starting Doses (2.5-5 mg)
Start at 5 mg (or lower at 2.5 mg) in patients who are: 1
- Debilitated
- Predisposed to hypotensive reactions
- Nonsmoking females ≥65 years of age
- Those with hepatic impairment 2
- Patients with Alzheimer's disease 2
- Elderly females with concern for oversedation or frailty 2
Dose escalation in these populations should be performed with caution 1
Adolescent Dosing (Ages 13-17)
- Start with 2.5-5 mg once daily, targeting 10 mg/day 1
- Use 2.5 or 5 mg increments when adjusting doses 1
- Clinical trials demonstrated efficacy with flexible dosing of 2.5-20 mg/day (mean modal dose 12.5 mg/day) 1
- Pharmacokinetic data suggest adolescents metabolize olanzapine similarly to nonsmoking adults, supporting the 5-10 mg starting dose guideline 3
Acute Agitation Dosing
Intramuscular Administration
- 10 mg IM is the standard dose for acute agitation (or 5-7.5 mg when clinically warranted) 2
- Alternative doses of 2.5 mg, 5 mg, or 7.5 mg IM can be used based on clinical factors 2
- Clinical trials demonstrated efficacy with IM doses ranging from 2.5-10 mg 2
Critical Safety Monitoring
Common Side Effects to Monitor
- Drowsiness and sedation (most common) 2
- Orthostatic hypotension - particularly important during initiation 2
- Weight gain - occurs in approximately 40% of patients, especially with high starting doses 4
- Metabolic effects with long-term use 2
Important Drug Interaction
- Exercise extreme caution when combining with benzodiazepines due to risk of oversedation and respiratory depression 2
- Fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine 2
Black Box Warning
- Increased mortality in elderly patients with dementia-related psychosis - this FDA warning must be considered when prescribing to elderly patients with cognitive impairment 2
Pharmacokinetic Considerations
- Peak plasma levels occur in 5-8 hours 4
- Half-life is approximately 35-37 hours, supporting once-daily dosing 4, 3
- Food does not affect absorption 5
- Smoking status significantly affects clearance - smokers may require higher doses 3
Common Pitfall to Avoid
Do not rush dose escalation. The most common error is increasing doses too rapidly before steady-state is achieved at one week. Doses above 10 mg/day should only be considered after clinical assessment confirms inadequate response, as higher doses were not more efficacious in registration trials 1. While some treatment-resistant patients may benefit from doses up to 20 mg/day or even higher in specialized settings 6, 7, this should be reserved for patients with severe, persistent symptoms and requires careful monitoring for increased weight gain and metabolic effects 7.