Dosing and Timing for Prozac (Fluoxetine) and Olanzapine
When combining fluoxetine and olanzapine, start with 5 mg olanzapine plus 20 mg fluoxetine taken once daily in the evening, without regard to meals. 1
Standard Combination Dosing (Olanzapine + Fluoxetine)
Initial Dosing
- Adults: Begin with olanzapine 5 mg + fluoxetine 20 mg once daily in the evening 1
- Children/Adolescents (10-17 years): Start with olanzapine 2.5 mg + fluoxetine 20 mg once daily in the evening 1
Dose Titration
- Adjust according to efficacy and tolerability within the range of olanzapine 5-12.5 mg and fluoxetine 20-50 mg for adults 1
- Proven efficacy range: Olanzapine 6-12 mg combined with fluoxetine 25-50 mg in clinical trials 1
- For pediatric patients, do not exceed olanzapine 12 mg with fluoxetine 50 mg 1
- Safety above olanzapine 18 mg with fluoxetine 75 mg has not been established 1
Timing Considerations
- Always administer in the evening as a single daily dose 1
- Can be taken with or without food 1
- Blood levels are measured 12 hours after evening dosing in clinical practice 2
Olanzapine Monotherapy Dosing
Standard Adult Dosing
- Target dose range: 10-20 mg/day for schizophrenia or bipolar disorder 3
- Maximum recommended dose: 20 mg/day 3, 1
- Doses above 20 mg/day show increased risk of weight gain and elevated prolactin without clear additional benefit in most patients 4
Special Populations Requiring Lower Doses
- Elderly or debilitated patients: Start with 2.5-5 mg daily 3
- Alzheimer's disease/dementia: Initial dose 2.5 mg once daily at bedtime, maximum 10 mg/day (usually divided twice daily) 3
- Intramuscular dosing: 5 mg/injection for geriatric patients; 2.5 mg/injection for debilitated or hypotension-prone patients 1
First-Episode Psychosis
- Initial target dose: 7.5-10 mg/day 5
- Increase doses only at widely spaced intervals (14-21 days) if response is inadequate 6
- Maximum 4 mg/day of risperidone is preferred in first-episode psychosis (when considering alternatives), as higher doses increase side effects without added benefit 6
Pediatric and Adolescent Considerations
Pharmacokinetic Differences
- Adolescent patients (10-18 years) achieve olanzapine concentrations similar to non-smoking adults 7
- Mean elimination half-life in adolescents: 37.2 hours 7
- Starting dose recommendation: 5-10 mg once daily with target of 10 mg/day is appropriate for most adolescents based on pharmacokinetics 7
Drug Interaction Considerations
Medications That Increase Olanzapine Levels
- CYP2D6 inhibitors increase olanzapine concentration-to-dose ratio by approximately 40% 2
- Consider dose reduction when combining with these agents 2
Medications That Decrease Olanzapine Levels
- Carbamazepine reduces olanzapine levels by approximately 36% 2
- Smoking may reduce olanzapine concentrations by up to 50% compared to non-smokers 7
- Higher doses may be needed in these situations 2
Expected Therapeutic Range
- With standard dosing (5-20 mg/day), 80% of patients achieve serum concentrations of 22-146 nmol/L (12-hour trough levels) 2
Treatment-Resistant Cases
Higher Dose Olanzapine (Off-Label)
- Case reports describe successful use of 35-60 mg/day in treatment-resistant schizophrenia 8
- Double-blind trials suggest doses above 20 mg/day may help selected patients with severe/persistent symptoms or acute agitation 4
- Critical caveat: Doses of 40 mg/day show increased weight gain and elevated prolactin compared to 20 mg/day 4
- This approach should be reserved for truly refractory cases after standard dosing fails 8
Palliative Care/Insomnia Dosing
- For insomnia in palliative care: Olanzapine 2.5-5 mg at bedtime 5
- This lower dose range is appropriate when the primary goal is sedation rather than antipsychotic effect 5
Key Safety Monitoring
- QTc prolongation: Occurs at maximum recommended doses, though olanzapine has the least effect among atypical antipsychotics 3
- Monitor orthostatic blood pressure, especially with intramuscular administration 1
- Assess for metabolic syndrome, weight gain, and elevated prolactin, particularly at higher doses 4, 9