Sertraline 100 mg to Fluoxetine Dose Equivalency
Based on the highest quality evidence from randomized controlled trials, sertraline 100 mg daily is approximately equivalent to fluoxetine 40 mg daily. 1
Evidence-Based Dose Conversion
The most rigorous method for determining antidepressant dose equivalency comes from a 2015 systematic analysis of 83 randomized, double-blind, flexible-dose trials involving 14,131 participants. 1 This study calculated weighted mean dose ratios and found that sertraline 98.5 mg/day is equivalent to fluoxetine 40 mg/day. 1 Therefore, sertraline 100 mg converts to approximately fluoxetine 40 mg.
Practical Conversion Approach
Start fluoxetine at 40 mg daily when switching from sertraline 100 mg, as this represents the evidence-based equivalent dose. 1
Consider initiating at fluoxetine 20 mg daily for 1 week, then increasing to 40 mg, particularly if the patient has anxiety symptoms or history of medication sensitivity, as 28% of patients cannot tolerate immediate initiation at 20 mg or higher. 2
Morning dosing is preferred for fluoxetine due to its activating properties and potential to cause insomnia. 3
Critical Pharmacokinetic Considerations
Fluoxetine has an exceptionally long half-life of 1-3 days for the parent compound and 4-16 days for its active metabolite norfluoxetine, meaning steady-state is not reached until 5-7 weeks after starting or changing doses. 3
No washout period is required when switching from sertraline to fluoxetine, as sertraline has a much shorter half-life and fluoxetine's long half-life provides built-in protection against discontinuation symptoms. 4
CYP2D6 poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and require starting at 10 mg daily with cautious titration, even when the calculated equivalent dose is 40 mg. 3 Consider genetic testing if the patient develops unexpected adverse effects at standard doses. 3
Monitoring After Conversion
Assess within 1-2 weeks after the switch for tolerability, but recognize that full therapeutic effects and side effects may not manifest for several weeks due to fluoxetine's long half-life. 3, 4
Wait 3-4 weeks between dose adjustments if titration is needed, not 1-2 weeks, due to the prolonged time to steady-state. 3
Use standardized rating scales to systematically assess symptom control during the transition period. 3
Common Pitfalls to Avoid
Do not assume immediate equivalency in clinical effect: While sertraline reaches steady-state in 1-2 weeks, fluoxetine requires 5-7 weeks, so patients may experience a temporary lag in symptom control during the transition. 3
Avoid dose escalation too quickly: If the patient does not respond adequately at 40 mg, wait at least 3-4 weeks before increasing, as plasma levels are still rising. 3
Be vigilant for drug interactions: Fluoxetine is a potent CYP2D6 inhibitor that can significantly increase levels of many medications (tricyclic antidepressants, antipsychotics, beta-blockers), creating risks not present with sertraline. 3
Monitor for increased activation or anxiety: Fluoxetine is more activating than sertraline, and some patients may experience increased anxiety or agitation, particularly during the first few weeks. 3, 2
Alternative Dosing Scenarios
For patients with panic disorder or significant anxiety: Start at fluoxetine 10 mg daily and increase by 5-10 mg increments every 3-4 weeks to reach the target of 40 mg, as these patients are particularly sensitive to initial SSRI side effects. 2
For elderly patients: Consider starting at 10 mg daily (50% of the standard dose) and titrating more cautiously, as older adults have significantly greater risk of adverse drug reactions. 3
If converting for OCD rather than depression: The equivalent dose may need to be higher (up to 60 mg fluoxetine), as OCD typically requires higher SSRI doses than depression. 3