What is the recommended initial dosage of fluoxetine (selective serotonin reuptake inhibitor) for a 45-year-old male with no significant medical history or current medications?

Fluoxetine Starting Dosage for a 45-Year-Old Man

Start fluoxetine at 20 mg once daily in the morning for this 45-year-old man with no significant medical history. 1

Initial Dosing Recommendation

• The FDA-approved starting dose is 20 mg/day administered in the morning, as controlled trials demonstrate this dose is sufficient to obtain a satisfactory response in major depressive disorder in most cases 1
• Morning administration is preferred because fluoxetine is activating and may cause insomnia if taken later in the day 2
• The full therapeutic effect may be delayed until 4 weeks of treatment or longer 1

Alternative Lower Starting Dose Strategy

• Consider starting at 10 mg daily (or 10 mg every other morning) if the patient has underlying anxiety or concerns about tolerability, as the American Academy of Family Physicians recommends this approach for patients where anxiety is a concern 2
• A subtherapeutic "test dose" strategy can help identify patients who may experience serotonergic overstimulation 2
• After 1 week at 10 mg/day, increase to the target dose of 20 mg/day if tolerated 1

Pharmacokinetic Considerations

• Fluoxetine has an exceptionally long half-life: 1-3 days for the parent compound and 4-16 days for its active metabolite norfluoxetine 2, 3, 4
• Due to this long half-life, side effects may not manifest for several weeks, and steady-state plasma levels are not reached until approximately 4 weeks 2, 3
• The long half-life means that even after dose adjustments, allow 3-4 weeks at a new dose before making further changes 5

Monitoring During Initial Treatment

• Monitor within 24-48 hours for behavioral activation, agitation, restlessness, insomnia, impulsiveness, and increased anxiety 5
• Assess treatment response using standardized symptom assessment after 4-6 weeks at the initial dose 5
• Be alert for common side effects including nausea, nervousness, insomnia, and headache 3, 4

Dose Escalation if Needed

• If insufficient clinical improvement is observed after several weeks at 20 mg/day, consider increasing the dose 1
• Doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon), with a maximum dose of 80 mg/day 1
• However, studies suggest that doses above 40 mg/day show decreased efficacy and increased adverse effects, indicating a potential therapeutic window 6

Common Pitfall to Avoid

• Do not increase the dose too quickly or assume treatment failure before 4 weeks, as fluoxetine's long half-life means therapeutic effects and side effects both develop gradually 2, 5
• If a patient appears to worsen or "relapse" after initial improvement, consider that this may represent serotonergic overstimulation rather than treatment failure—in such cases, lowering the dose may be more effective than increasing it 6