What is the recommended dosing for delayed release weekly fluoxetine (selective serotonin reuptake inhibitor)?

Delayed-Release Weekly Fluoxetine Dosing

The delayed-release weekly fluoxetine formulation is dosed at 90 mg once weekly, initiated 7 days after the last daily dose of fluoxetine 20 mg. 1

Initiation and Transition Protocol

• Start with daily fluoxetine 20 mg for at least 12-13 weeks to establish response before transitioning to weekly dosing 1, 2
• Wait exactly 7 days after the last 20 mg daily dose before administering the first 90 mg weekly capsule 1
• This 7-day interval prevents transient increases in steady-state fluoxetine concentrations that occur when transitioning the next day 1

Standard Weekly Dosing

• The only FDA-approved weekly dose is 90 mg once weekly for maintenance treatment of major depressive disorder 1
• Weekly dosing maintains efficacy comparable to daily 20 mg dosing, with cumulative relapse rates remaining similar over 25 weeks 2
• Peak fluoxetine concentrations from the 90 mg weekly dose are approximately 1.7-fold higher than daily 20 mg dosing, but average steady-state concentrations are about 50% lower 1

Monitoring and Adjustment

• If response is not maintained on weekly dosing, reestablish daily dosing regimen rather than increasing the weekly dose 1
• Therapeutic equivalence for delaying relapse has not been formally established between weekly and daily formulations, though efficacy appears similar 1, 2
• The weekly formulation produces greater fluctuation between peak and trough levels (164% for fluoxetine, 43% for norfluoxetine) compared to daily dosing 1

Special Populations

• In hepatic impairment, use lower or less frequent dosing due to prolonged elimination half-life (mean 7.6 days vs. 2-3 days in normal liver function) 1
• Elderly patients may require dose adjustment, though no unusual age-related adverse events were observed in patients ≥60 years receiving daily fluoxetine 1
• Renal impairment does not routinely require dosage adjustment, as steady-state concentrations in dialysis patients are comparable to those with normal renal function 1

Clinical Pearls

• Compliance improves with weekly dosing: compliance remained at 87.5% with weekly fluoxetine versus declining from 87.3% to 79.4% with continued daily dosing (p<0.001) 3
• The long half-lives of fluoxetine (4-6 days) and norfluoxetine (4-16 days) enable once-weekly administration 2, 4
• Active drug persists for weeks after discontinuation due to the long elimination half-life, requiring at least 5 weeks before starting an MAOI 1
• Higher weekly doses (up to 180 mg) have been reported in hemodialysis patients but are not FDA-approved and may cause increased side effects including restlessness, dry mouth, and sedation 5

Common Pitfalls

• Do not transition to weekly dosing before establishing response on daily therapy (minimum 12-13 weeks) 1, 2
• Do not increase the weekly dose beyond 90 mg as standard practice; instead return to daily dosing if response is inadequate 1
• Do not transition the next day from daily to weekly dosing without considering the 7-day washout period to avoid concentration spikes 1