Recommended Sertraline Dose When Switching from Fluoxetine 20 mg
Switch to sertraline 50 mg by mouth daily when converting from fluoxetine 20 mg daily. 1
Evidence-Based Dose Equivalence
The most rigorous dose-equivalence study, which analyzed 83 randomized controlled trials with over 14,000 participants, established that fluoxetine 40 mg daily is equivalent to sertraline 98.5 mg daily 1. Using this conversion ratio:
- Fluoxetine 20 mg (half of 40 mg) converts to approximately sertraline 50 mg daily 1
- This represents a 1:2.5 conversion ratio (20 mg fluoxetine → 50 mg sertraline) 1
Clinical Validation of the Conversion
Multiple clinical studies support this dosing strategy:
- A Veterans Affairs study demonstrated that converting fluoxetine to sertraline at a ratio of 50 mg sertraline per 20 mg fluoxetine maintained depression control without loss of efficacy 2
- The American College of Physicians recommends direct switching between SSRIs without washout periods, starting sertraline at 50 mg when transitioning from other SSRIs 3
- Sertraline 50 mg represents the standard initial therapeutic dose with established efficacy in major depressive disorder 4, 5
Practical Switching Algorithm
Day 1 of switch:
- Stop fluoxetine 20 mg 3
- Start sertraline 50 mg the next day without washout period 3
- No overlap or tapering required when switching between these SSRIs 3
Weeks 2-4:
- Monitor for therapeutic response and tolerability 3
- If inadequate response after 2-4 weeks, titrate to 100 mg daily 3
- Maximum dose 200 mg daily if needed, though most patients respond to 50-100 mg 4, 5
Important Caveats
Fluoxetine's long half-life: Fluoxetine and its active metabolite norfluoxetine have half-lives of 1-3 days and 7-15 days respectively, meaning fluoxetine will continue exerting serotonergic effects for weeks after discontinuation 6. This built-in "washout" reduces discontinuation syndrome risk but means full sertraline effects may not be apparent immediately 6.
Why NOT 25 mg: This dose is subtherapeutic for depression and would delay therapeutic response 3. The 25 mg dose is only appropriate for initial tolerability testing in highly sensitive patients, not for standard SSRI switching 3.
Why NOT 100 mg initially: Starting at 100 mg provides no additional benefit over 50 mg in most patients and increases the risk of side effects including sexual dysfunction 7, 5. Dose escalation should only occur after assessing response at 50 mg 7.
Why NOT 200 mg: This represents a 10-fold equivalent dose (fluoxetine 80 mg equivalent) and would constitute overdosing, significantly increasing adverse effects without proportional efficacy gains 1, 5.
Monitoring Requirements
- Assess for discontinuation symptoms (dizziness, fatigue, headaches, nausea) in the first 1-2 weeks, though these are less common with fluoxetine due to its long half-life 6, 3
- Monitor for therapeutic response at 2-4 weeks 3
- Screen for sexual dysfunction, as sertraline causes this in approximately 14% of males and 6% of females 8
- Watch for serotonin syndrome symptoms during the transition period, though risk is low with appropriate switching 3