What is the equivalent dose of Prozac (fluoxetine) for a patient taking 100 mg of Zoloft (sertraline)?

Sertraline 100 mg to Fluoxetine Dose Equivalency

Sertraline 100 mg is approximately equivalent to fluoxetine 40 mg based on the most rigorous dose equivalency analysis from randomized controlled trials. 1

Evidence-Based Dose Conversion

The most robust evidence comes from a systematic analysis of 83 randomized, double-blind, flexible-dose trials involving 14,131 participants, which calculated weighted mean dose ratios to establish equivalencies. 1 This study found that sertraline 98.5 mg/day is equivalent to fluoxetine 40 mg/day, making the conversion ratio approximately 2.5:1 (sertraline:fluoxetine). 1

Practical Application

For your patient taking sertraline 100 mg:

• Direct conversion: Fluoxetine 40 mg daily 1
• This represents the evidence-based equivalent dose derived from actual clinical trial data rather than arbitrary consensus methods 1

Clinical Context and Titration Considerations

Important pharmacokinetic differences exist between these medications that affect switching strategies:

• Fluoxetine has an exceptionally long half-life (1-3 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine), meaning side effects may not manifest for several weeks 2
• Sertraline has a much shorter half-life (approximately 26 hours), requiring different washout considerations 1

Switching Protocol

When converting from sertraline 100 mg to fluoxetine:

1. Consider starting fluoxetine at 20 mg daily initially (half the equivalent dose) to minimize activation and anxiety, which are recognized initial adverse effects of SSRIs, particularly fluoxetine 2
2. Titrate to 40 mg after 3-4 weeks if tolerated and clinically indicated, as fluoxetine's long half-life requires longer intervals between dose adjustments 2
3. Monitor weekly during the transition for behavioral activation, agitation, or increased anxiety 2

Supporting Evidence from Comparative Trials

Multiple head-to-head trials confirm similar efficacy between sertraline and fluoxetine at their respective therapeutic doses:

• Studies comparing sertraline 50-150 mg with fluoxetine 20-60 mg showed equivalent efficacy on depression rating scales 3, 4
• A 10-week trial found that sertraline 100 mg and fluoxetine 20 mg demonstrated similar response rates by week 6 (43% vs 31%, respectively) 5

Critical Pharmacogenetic Consideration

CYP2D6 poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and are at significantly higher risk of toxicity even at standard doses. 2 If your patient has known CYP2D6 poor metabolizer status or develops unexpected adverse effects, consider:

• Starting at fluoxetine 10 mg daily or even 10 mg every other day 2
• Genetic testing if severe adverse effects occur at standard doses 6

Common Pitfalls to Avoid

• Do not use fluoxetine 20 mg as the equivalent dose for sertraline 100 mg, as this represents underdosing based on the dose equivalency data 1
• Do not increase fluoxetine doses at 1-2 week intervals; the long half-life requires 3-4 week intervals to reach steady state 2
• Do not exceed fluoxetine 20 mg daily in elderly patients without careful monitoring, as higher doses increase QT prolongation risk 7