Sertraline 100mg to Fluoxetine Dose Equivalency
Based on the highest quality evidence from randomized controlled trials, sertraline 100mg is approximately equivalent to fluoxetine 40mg daily. 1
Evidence-Based Dose Conversion
The most rigorous systematic analysis of antidepressant dose equivalency, which examined 83 randomized controlled trials with over 14,000 participants, established that sertraline 98.5mg/day is equivalent to fluoxetine 40mg/day. 1 This translates to a conversion ratio of approximately 2.5:1 (sertraline:fluoxetine).
Practical Application
- For a patient taking sertraline 100mg, the equivalent fluoxetine dose is 40mg daily. 1
- This conversion is based on weighted mean dose ratios from flexible-dose comparative trials, making it the most evidence-based approach available. 1
Important Switching Considerations
Pharmacokinetic Differences
- Fluoxetine has an exceptionally long half-life (1-3 days for parent compound, 4-16 days for active metabolite norfluoxetine), taking 5-7 weeks to reach steady-state, which creates unique challenges when switching from sertraline. 2
- Sertraline has a 24-hour half-life with predictable, dose-proportional pharmacokinetics, allowing steady-state within 1 week. 2
Recommended Switching Strategy
- Start fluoxetine 40mg daily the day after the last sertraline dose, as the rapid clearance of sertraline (gone within 5-7 days) requires immediate initiation of the replacement SSRI. 2
- Monitor closely for the first 2-4 weeks as fluoxetine gradually reaches therapeutic levels over several weeks due to its prolonged half-life. 2
Critical Safety Warnings
CYP2D6 Considerations
- If the patient is a CYP2D6 poor metabolizer, they may experience 3.9 to 11.5-fold higher fluoxetine levels even at standard doses, significantly increasing toxicity risk. 2, 3
- Consider starting at fluoxetine 10mg daily in known poor metabolizers, as the FDA has issued safety warnings about QT prolongation risk in this population. 3
- Unexpected adverse effects at standard fluoxetine doses should prompt CYP2D6 testing. 2
Monitoring Requirements
- Watch for discontinuation syndrome symptoms during the first week, though less likely with the immediate fluoxetine start. 2
- Monitor for serotonin syndrome risk in the first 24-48 hours, particularly if the patient takes other serotonergic medications. 2
- Assess for return of depressive or anxiety symptoms at weeks 2,4, and 8, as therapeutic effect should be maintained throughout the switch if dose equivalency is appropriate. 2
Clinical Context from Comparative Trials
Multiple head-to-head trials demonstrated comparable efficacy between sertraline 50-100mg and fluoxetine 20-40mg in treating major depression, supporting the dose equivalency calculations. 4, 5, 6 Response rates were similar between groups, with 69% for sertraline and 67% for fluoxetine in one large trial. 4