Prozac (Fluoxetine) Dosing in Adults
Start fluoxetine at 20 mg once daily in the morning for most adults with depression, as this dose is sufficient to obtain a satisfactory response in the majority of cases. 1
Initial Dosing Strategy
- Standard starting dose: 20 mg once daily in the morning is recommended by the FDA for major depressive disorder in adults, as controlled trials demonstrate this dose achieves satisfactory response in most patients 1
- Alternative low-dose initiation: 10 mg daily or every other morning may be considered for patients with anxiety sensitivity or concern about tolerability, as the American Academy of Family Physicians notes fluoxetine is activating and may cause insomnia 2
- Research supports that 28% of patients cannot tolerate the full 20 mg dose but benefit from lower doses (5-10 mg), particularly those with concurrent panic disorder 3
Dose Escalation
- If insufficient clinical improvement after several weeks at 20 mg, increase the dose to 40 mg or 60 mg daily, with a maximum of 80 mg/day 1
- Doses above 20 mg may be given once daily (morning) or twice daily (morning and noon) 1
- Allow 4 weeks or longer for full antidepressant effect before declaring treatment failure, as the full therapeutic response may be delayed 1
- For patients who relapse on 20 mg during maintenance treatment, increasing to 40 mg achieves response in 57-67% of cases 4, 5
Critical Pharmacokinetic Considerations
- Fluoxetine has an exceptionally long half-life: 1-3 days for the parent compound and 4-16 days for active metabolite norfluoxetine, meaning steady-state is not reached until 5-7 weeks after dose changes 2
- CYP2D6 poor metabolizers require cautious dosing starting at 10 mg daily due to 3.9 to 11.5-fold higher fluoxetine levels and significantly increased toxicity risk, with FDA safety warnings about QT prolongation 2
- If unexpected adverse effects occur at standard doses, consider CYP2D6 genetic testing 2
Maintenance Treatment
- Continue treatment for 4-9 months after satisfactory response in patients with first episode of major depressive disorder 2
- For recurrent depression (2+ episodes), consider years to lifelong maintenance therapy 2
- Efficacy is maintained for up to 38 weeks following acute treatment at 20 mg/day 1
Special Population Adjustments
- Elderly patients: Use lower or less frequent dosing, approximately 50% of standard adult starting dose, as older adults are at significantly greater risk of adverse drug reactions 2, 1
- Hepatic impairment: Use lower or less frequent dosing 1
- Renal impairment does not routinely require dosage adjustments 1
Common Pitfalls to Avoid
- Do not increase doses more frequently than every 3-4 weeks due to the long half-life; side effects may not manifest for several weeks after dose changes 2
- Do not exceed 80 mg/day maximum dose 1
- Morning dosing is preferred as fluoxetine is activating and may cause insomnia if taken later in the day 2
- Do not prematurely switch medications before allowing adequate trial duration (6-8 weeks at therapeutic dose) 2