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

Fluoxetine Dosing Recommendations

Initial Dosing for Major Depressive Disorder

For adults with 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

• For pediatric patients (children and adolescents), initiate treatment at 10 mg/day for one week, then increase to 20 mg/day 1
• In lower weight children, the starting and target dose may remain at 10 mg/day, with consideration for increasing to 20 mg/day after several weeks if insufficient clinical improvement is observed 1
• Morning dosing is strongly preferred due to fluoxetine's activating properties, which can cause insomnia if taken later in the day 2, 3

Dose Titration Strategy

If insufficient clinical improvement is observed after several weeks at 20 mg/day, consider dose increases, but do so cautiously given fluoxetine's very long half-life. 1

• Fluoxetine has a half-life of 1-3 days, with its active metabolite norfluoxetine having a half-life of 4-16 days, meaning side effects may not manifest for several weeks 2, 3
• When increasing doses, use 3-4 week intervals rather than 1-2 weeks due to the long half-life 2
• Use the smallest available increments (5-10 mg increases) to minimize adverse effects 2
• 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

Indication-Specific Dosing

Obsessive-Compulsive Disorder

• Adults: Start at 20 mg/day in the morning; doses of 20-60 mg/day are recommended, though up to 80 mg/day have been well tolerated 1
• Adolescents and higher weight children: Start at 10 mg/day for 2 weeks, then increase to 20 mg/day, with a recommended range of 20-60 mg/day 1
• Lower weight children: Start at 10 mg/day with a recommended range of 20-30 mg/day 1

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 frequency. 1
• For some patients, titrate up to this target dose over several days 1

Maintenance Treatment

For major depressive disorder, continue treatment for 4 weeks or longer to achieve full therapeutic effect, with maintenance therapy for several months after remission. 1

• Daily dosing at 20 mg/day maintains efficacy for up to 38 weeks following acute treatment 1
• Weekly dosing option: After stabilization on fluoxetine 20 mg daily for at least 13 weeks, patients may be switched to fluoxetine 90 mg once weekly, initiated 7 days after the last daily dose 1, 4
• If satisfactory response is not maintained with weekly dosing, reestablish a daily dosing regimen 1
• Alternative maintenance strategy: Once patients are panic-free or in remission, some may be maintained on once-weekly dosing ranging from 10-60 mg 5

Management of Inadequate Response or Relapse

If a patient relapses on fluoxetine 20 mg/day during long-term treatment, increasing the dose to 40 mg/day is effective, with 67% achieving full response. 6

• If increased anxiety or agitation occurs after dose escalation, immediately reduce back to the previous tolerated dose 2
• Consider adding cognitive behavioral therapy to the current tolerated dose rather than increasing medication, as combination therapy shows superior outcomes 2

Special Population Considerations

• Hepatic impairment: Use a lower or less frequent dosage 1
• Elderly patients: Consider lower or less frequent dosing 1
• CYP2D6 poor metabolizers: May experience 3.9 to 11.5-fold higher fluoxetine levels; consider genetic testing if poor tolerance or unusual response occurs at standard doses 2
• Cardiac risk factors: Use with caution in patients with congenital long QT syndrome, previous QT prolongation, or family history of long QT syndrome 3
• Renal impairment: Dosage adjustments are not routinely necessary 1

Critical Safety Considerations

• Allow at least 5 weeks (perhaps longer) after stopping fluoxetine before starting an MAOI due to the long half-life; allow at least 14 days between stopping an MAOI and starting fluoxetine. 1
• Monitor for serotonin syndrome symptoms (confusion, agitation, tremors, hyperreflexia, autonomic instability), particularly after dose increases or when combining with other serotonergic medications 7
• When coadministering with tricyclic antidepressants, TCA dosage may need reduction and plasma concentrations may require monitoring 1
• The most frequently occurring adverse event is insomnia, occurring more frequently than placebo 8, 9