What is the typical dosing regimen for Prozac (fluoxetine)?

Prozac (Fluoxetine) Dosing

Standard Adult Dosing for Major Depressive Disorder

For major depressive disorder, 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
• Dose increases may be considered after several weeks if insufficient clinical improvement is observed 1
• The maximum dose should not exceed 80 mg/day 1
• Doses above 20 mg/day can be given once daily (morning) or twice daily (morning and noon) 1
• Full therapeutic effect may be delayed until 4 weeks of treatment or longer 1

Alternative Low-Dose Strategy

For patients with anxiety disorders or panic disorder comorbid with depression, starting at 5-10 mg/day and titrating slowly is advisable, as approximately 28% of patients cannot tolerate the standard 20 mg dose. 2

• Research demonstrates that 14% of patients benefit from doses lower than 20 mg/day, while another 14% cannot tolerate any dose 2
• Patients with panic disorder are particularly intolerant of the standard 20 mg starting dose 2
• The American Academy of Family Physicians recommends starting with 10 mg every other morning or 10 mg daily for some patients 3

Pediatric Dosing (Children and Adolescents)

In pediatric patients with major depressive disorder, initiate treatment at 10 mg/day for one week, then increase to 20 mg/day. 1

• Lower weight children may remain at 10 mg/day as both starting and target dose 1
• After several weeks at 20 mg/day, dose increases may be considered if insufficient clinical improvement is observed 1

Obsessive-Compulsive Disorder Dosing

For OCD in adults, start at 20 mg/day in the morning, with a therapeutic range of 20-60 mg/day, though doses up to 80 mg/day have been well tolerated. 1

• Full therapeutic effect may be delayed until 5 weeks of treatment or longer 1
• In adolescents and higher weight children with OCD, start at 10 mg/day for 2 weeks, then increase to 20 mg/day 1
• In lower weight children with OCD, start at 10 mg/day with a recommended dose range of 20-30 mg/day 1

Bulimia Nervosa Dosing

For bulimia nervosa, the recommended dose is 60 mg/day administered in the morning, as only this dose was statistically superior to placebo in reducing binge-eating and vomiting. 1

• Titrate up to the 60 mg target dose over several days for some patients 1
• Doses above 60 mg/day have not been systematically studied in bulimia 1

Maintenance Treatment Options

For maintenance treatment of major depressive disorder, fluoxetine can be continued at 20 mg/day or switched to a once-weekly 90 mg formulation after stabilization. 1

• Weekly dosing should be initiated 7 days after the last daily 20 mg dose 1
• If satisfactory response is not maintained with weekly dosing, reestablish a daily dosing regimen 1
• Compliance with once-weekly fluoxetine (87.8%) is significantly better than once-daily dosing (79.0%) during continuation treatment 4

Pharmacokinetic Considerations

Fluoxetine has an exceptionally long half-life of 1-3 days for the parent compound and 4-16 days for its active metabolite norfluoxetine, which means side effects may not manifest for several weeks. 3, 5

• After long-term administration, the elimination half-life averages 4 days for fluoxetine and 7 days for norfluoxetine 5
• The long half-life essentially precludes withdrawal phenomena 6
• Morning dosing is preferred as fluoxetine is activating and may cause insomnia if taken later in the day 3

Special Populations

In patients with hepatic impairment, elderly patients, or those with multiple concomitant medications, use a lower or less frequent dosage. 1

• Dosage adjustments for renal impairment are not routinely necessary 1
• CYP2D6 poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and are at higher risk of toxicity 7
• The FDA warns that fluoxetine should be used with caution in CYP2D6 poor metabolizers due to risk of QT prolongation 7

Common Pitfalls and Caveats

The most common adverse events at the recommended 20 mg/day dose are gastrointestinal (nausea, diarrhea) and nervous system effects (anxiety, insomnia, nervousness, headache). 6, 5

• Adverse events are dose-related and more common at higher doses 6
• Fluoxetine is a potent CYP2D6 inhibitor, increasing potential for drug interactions, though most are not clinically important 6
• At least 5 weeks should elapse after stopping fluoxetine before starting an MAOI due to the long half-life 1
• At least 14 days should elapse between discontinuing an MAOI and starting fluoxetine 1