Fluoxetine 60mg to Sertraline Dose Equivalency
Direct Dose Conversion
Fluoxetine 60mg daily is approximately equivalent to sertraline 150mg daily, using a 1:2.5 conversion ratio. 1, 2
Evidence-Based Conversion Ratios
The most clinically validated conversion approach comes from direct switching studies:
A randomized controlled trial established that 50mg sertraline is equivalent to 20mg fluoxetine (a 2.5:1 ratio), with both doses serving as the starting dose in 76% of patients and producing equivalent efficacy and tolerability. 1
A Veterans Affairs study confirmed this conversion ratio, demonstrating that 50-75mg sertraline per 20mg fluoxetine successfully maintained depression control when switching patients, with the higher ratio (75mg:20mg or 3.75:1) showing more improvement. 2
Using the conservative 2.5:1 ratio: 60mg fluoxetine × 2.5 = 150mg sertraline. 1, 2
Using the higher ratio from the VA study: 60mg fluoxetine × 3.75 = 225mg sertraline (though this exceeds typical dosing and the 2.5:1 ratio is more widely validated). 2
Critical Pharmacokinetic Considerations Before Switching
Fluoxetine's exceptionally long half-life (1-3 days for parent compound, 4-16 days for active metabolite norfluoxetine) means it takes 5-7 weeks to reach steady-state or wash out, creating unique switching challenges not present with other SSRIs. 3, 4
Sertraline has a 24-hour half-life with dose-proportional pharmacokinetics, allowing predictable dose adjustments at 1-2 week intervals, in stark contrast to fluoxetine's prolonged and non-linear kinetics. 5, 4
Fluoxetine at 60mg produces greater-than-expected plasma concentrations due to non-linear pharmacokinetics, particularly in CYP2D6 poor metabolizers who have 3.9 to 11.5-fold higher levels even at standard doses. 6, 3
If the patient is a CYP2D6 poor metabolizer on fluoxetine 60mg, they may have toxic fluoxetine levels, and switching to sertraline (which has minimal CYP450 effects) may require starting at lower doses like 50-100mg rather than the full calculated equivalent. 6, 3, 5
Practical Switching Strategy
Direct switch without washout period:
Start sertraline at 150mg daily the day after the last fluoxetine dose, as the prolonged half-life of fluoxetine provides a natural taper effect during the transition. 2, 7
Monitor closely for the first 2-4 weeks, as fluoxetine levels will still be declining while sertraline reaches steady-state within 1 week. 5, 4
Sertraline can be titrated at 1-2 week intervals if needed (unlike fluoxetine which requires 3-4 week intervals), with the therapeutic range being 50-200mg daily. 5
Safety Monitoring During Transition
Watch for discontinuation syndrome symptoms (dizziness, fatigue, myalgias, headaches, nausea, sensory disturbances), though these are less likely with fluoxetine due to its long half-life providing self-tapering. 5
Monitor for serotonin syndrome risk in the first 24-48 hours, particularly if the patient is on other serotonergic medications, though the gradual decline of fluoxetine levels reduces this risk compared to other SSRI switches. 5
Assess for return of depressive or anxiety symptoms at weeks 2,4, and 8, as the therapeutic effect should be maintained throughout the switch if the dose equivalency is appropriate. 5, 1
If unexpected adverse effects occur or the patient seems unusually sensitive, consider CYP2D6 testing, as poor metabolizers may have had elevated fluoxetine levels that masked the true therapeutic dose needed. 6, 3
Common Pitfalls to Avoid
Do not use a 1:1 conversion ratio (60mg fluoxetine to 60mg sertraline), as this significantly underdoses and risks relapse. 1, 2
Do not implement a washout period before starting sertraline, as fluoxetine's long half-life makes this unnecessary and increases relapse risk. 2, 7
Do not increase sertraline dose before 1-2 weeks, as steady-state is reached quickly and early dose escalation increases adverse effects without improving efficacy. 5
Do not assume the patient was at an appropriate fluoxetine dose - if they were a CYP2D6 poor metabolizer, 60mg may have produced toxic levels, and the equivalent sertraline dose might be lower than calculated. 6, 3