What is the recommended dosing for fluoxetine (Selective Serotonin Reuptake Inhibitor)?

Fluoxetine Dosing Recommendations

Standard Initial Dosing for Adults

For major depressive disorder in adults, start fluoxetine at 20 mg once daily in the morning, as this dose is sufficient to obtain a satisfactory response in most cases. 1

• The FDA-approved initial dose is 20 mg/day administered in the morning 1
• Studies comparing 20,40, and 60 mg/day to placebo demonstrate that 20 mg/day achieves adequate efficacy in most patients with major depression 1
• Maximum dose should not exceed 80 mg/day 1

Alternative Low-Dose Initiation Strategy

For patients with anxiety disorders or panic disorder, consider starting at 10 mg/day (or even 10 mg every other morning) to minimize activation side effects, then increase to 20 mg after 1-2 weeks. 2, 1

• The American Academy of Family Physicians recommends starting with 10 mg every other morning or 10 mg daily for some patients 2
• For panic disorder specifically, the FDA label recommends initiating at 10 mg/day for 1 week, then increasing to 20 mg/day 1
• Research shows that 28% of depressed patients cannot tolerate the full 20 mg dose, with half of these benefiting from lower doses 3

Pediatric Dosing

In children and adolescents with depression, start at 10 mg/day for 1 week, then increase to 20 mg/day, with a maximum of 60 mg/day. 4, 1

• Lower weight children may remain at 10 mg/day as both starting and target dose 1
• For OCD in adolescents and higher weight children, start at 10 mg/day for 2 weeks, then increase to 20 mg/day 1
• Lower weight children with OCD should target 20-30 mg/day range 1

Condition-Specific Dosing

Obsessive-Compulsive Disorder

Start at 20 mg/day in the morning; doses of 20-60 mg/day are recommended, though up to 80 mg/day may be used. 1

• No clear dose-response relationship was demonstrated in one study, but another suggested possible benefit from higher doses 1
• Full therapeutic effect may be delayed until 5 weeks or longer 1

Bulimia Nervosa

The recommended dose is 60 mg/day administered in the morning, as only this dose was statistically superior to placebo. 1

• Titrate up to 60 mg over several days if needed for tolerability 1
• The 20 mg dose was not effective in controlled trials 1

Panic Disorder

Start at 10 mg/day for 1 week, then increase to 20 mg/day (the most frequently administered effective dose). 1

• Doses above 60 mg/day have not been systematically evaluated 1

Dose Titration Principles

When increasing fluoxetine doses, wait 3-4 weeks between adjustments due to the long half-life (1-3 days for fluoxetine, 4-16 days for norfluoxetine), and use small increments of 5-10 mg. 2

• The American Academy of Child and Adolescent Psychiatry specifically recommends against 1-2 week intervals 2
• Side effects may not manifest for several weeks due to the long half-life 2, 5
• If dose escalation causes increased anxiety, immediately reduce back to the previous tolerated level 2

Special Population Adjustments

Elderly Patients

Maximum dose for elderly patients is 20 mg every morning due to age-related pharmacokinetic changes. 4

• Lower or less frequent dosing should be used 1

Hepatic Impairment

Use lower or less frequent dosing in patients with hepatic impairment. 1

Renal Impairment

Dosage adjustments for renal impairment are not routinely necessary. 1

Timing and Administration

Administer fluoxetine in the morning to avoid insomnia, as it has activating properties. 2, 5

• Doses above 20 mg/day may be given once daily (morning) or twice daily (morning and noon) 1
• The long half-life allows for flexible dosing schedules 5

Maintenance Dosing

For maintenance treatment of depression, 20 mg/day has been shown effective for up to 50 weeks total (38 weeks maintenance following 12 weeks acute treatment). 1

• Weekly dosing with 90 mg capsules (Prozac Weekly) may be initiated 7 days after the last 20 mg daily dose 1
• If response is not maintained with weekly dosing, reestablish daily dosing 1

Critical Safety Considerations

Fluoxetine inhibits CYP2D6 and other cytochrome P450 enzymes, increasing drug interaction potential, particularly at higher doses. 4, 6

• CYP2D6 poor metabolizers may have 3.9 to 11.5-fold higher fluoxetine levels, potentially causing toxicity at standard doses 2
• Use caution in patients with congenital long QT syndrome or family history of QT prolongation 5
• Allow at least 5 weeks after stopping fluoxetine before starting an MAOI due to the long half-life 1

Common Pitfalls to Avoid

• Do not increase doses at 1-2 week intervals—the long half-life requires 3-4 weeks to reach steady state 2
• Do not start at 20 mg in anxious patients or those with panic disorder—use 10 mg or lower to minimize activation 2, 1, 3
• Do not assume higher doses are more effective—20 mg is sufficient for most patients with depression, and higher doses increase adverse effects without clear efficacy benefit 2, 1, 7