Starting Dose of Prozac (Fluoxetine) for Adult Depression
For adult patients with major depressive disorder, start fluoxetine at 20 mg once daily in the morning. 1
Standard Adult Dosing
- The FDA-approved starting dose is 20 mg/day administered in the morning, which is sufficient to obtain a satisfactory response in most cases of major depressive disorder 1
- Clinical trials demonstrate that 20 mg/day provides significant efficacy with optimal tolerability, showing significantly greater remission and response rates compared to placebo (p < .001) 2
- At the standard 20 mg/day dose, only nausea and insomnia occur significantly more frequently than placebo, whereas higher doses (60 mg/day) are associated with additional adverse events including anxiety and dizziness 3
Alternative Lower-Dose Strategy for Specific Populations
Consider starting at 10 mg/day (or even 5 mg/day) and titrating up in patients with:
- Concurrent panic disorder, as these patients frequently cannot tolerate the standard 20 mg dose 4
- High anxiety sensitivity, since fluoxetine is activating and may cause initial anxiety symptoms 5
- History of medication sensitivity, as approximately 28% of patients cannot tolerate the full 20 mg dose but respond well to lower doses 4
Low-Dose Titration Protocol
- Start at 10 mg daily (or 10 mg every other morning for highly sensitive patients) 5
- Increase to 20 mg after 1 week if tolerated 1
- Due to fluoxetine's exceptionally long half-life (1-3 days for parent compound, 4-16 days for active metabolite norfluoxetine), allow 3-4 weeks between dose adjustments to reach steady state 5
- Morning dosing is strongly preferred due to activating properties that may cause insomnia if taken later in the day 5
Special Population Considerations
Elderly Patients
- Use lower or less frequent dosing in elderly patients (approximately 50% of the standard adult starting dose) 6, 7, 1
- Older adults are at significantly greater risk of adverse drug reactions 6
CYP2D6 Poor Metabolizers
- Start at 10 mg daily with cautious titration in patients with known or suspected CYP2D6 poor metabolizer status 5
- Poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and are at significantly increased risk of toxicity even at standard doses 5
- Consider CYP2D6 genetic testing if unexpected adverse effects develop at standard doses 5
- The FDA has issued safety warnings regarding QT prolongation risk in this population 5
Hepatic Impairment
- Lower or less frequent dosing should be used in patients with hepatic impairment 1
Critical Timing Considerations
- Full antidepressant effect may be delayed until 4 weeks of treatment or longer 1
- Steady-state plasma concentrations are not reached until approximately 5-7 weeks after initiating or changing the dose due to the long half-life 5
- This extended time to steady state means side effects may not manifest for several weeks after dose initiation or changes 5
Common Pitfalls to Avoid
- Do not increase the dose too rapidly: Allow at least 3-4 weeks between dose adjustments, not 1-2 weeks, due to the long half-life 5
- Do not assume treatment failure too early: Some patients who appear to "fail" at 20 mg may actually be experiencing serotonergic overstimulation and respond better to lower doses (10 mg or even 5 mg) 8
- Do not dismiss initial anxiety as treatment failure: Increased anxiety and agitation are recognized initial adverse effects that often resolve with continued treatment at the same dose or reduction to a lower dose 5