What is the recommended dosage of fluoxetine (Selective Serotonin Reuptake Inhibitor) for adults?

Fluoxetine Dosage for Adults

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

Initial Dosing Strategy

• The FDA-approved starting dose is 20 mg/day administered in the morning. 1
• A lower starting dose of 10 mg every other morning (or 10 mg daily) may be considered in specific populations, particularly elderly patients or those with concurrent medical conditions. 2
• For patients prone to anxiety or activation symptoms, starting at 10 mg daily or even 5 mg daily with gradual titration may reduce early adverse effects and improve tolerability. 3

Dose Escalation

• If insufficient clinical improvement occurs after several weeks at 20 mg/day, consider increasing the dose. 1
• The FDA-approved maximum dose is 80 mg/day, though doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon). 1
• Due to fluoxetine's very long half-life (1-3 days for fluoxetine, 4-16 days for norfluoxetine), dose adjustments should be made slowly, with intervals of 3-4 weeks between increases, as side effects may not manifest for several weeks. 2, 4

Maintenance Treatment

• The full antidepressant effect may be delayed until 4 weeks of treatment or longer. 1
• Efficacy is maintained for up to 38 weeks following acute treatment at 20 mg/day. 4, 1
• After achieving remission, continue treatment for several months or longer, as acute episodes of major depressive disorder require sustained pharmacologic therapy. 1

Special Populations and Considerations

• Use lower or less frequent dosing in patients with hepatic impairment, elderly patients, or those on multiple concomitant medications. 1
• Dosage adjustments for renal impairment are not routinely necessary. 1
• For CYP2D6 poor metabolizers, exercise extreme caution as they have 3.9 to 11.5-fold higher fluoxetine levels and are at significantly higher risk of toxicity even at standard doses. 4

Common Pitfalls to Avoid

• Do not escalate doses too rapidly. The long half-life means steady-state levels take approximately 4 weeks to achieve, so premature dose increases can lead to accumulation and increased adverse effects. 2, 4
• Morning dosing is preferred as fluoxetine is activating and may cause insomnia if taken later in the day. 2, 1
• If a patient cannot tolerate 20 mg/day, do not automatically discontinue—approximately 28% of patients benefit from lower doses (5-15 mg/day). 3
• Higher doses (above 20 mg/day) are associated with more adverse effects without clear evidence of superior efficacy in most patients. 4, 5

Adverse Effects Profile

• Common side effects at 20 mg/day include nausea, nervousness, insomnia, headache, sweating, tremors, dizziness, and gastrointestinal and sexual disturbances. 2, 5
• The incidence of adverse events leading to discontinuation at 20 mg/day is similar to placebo (6.1% vs 5.8%). 5
• Fluoxetine is significantly safer in overdose compared to tricyclic antidepressants and does not cause cardiac conduction abnormalities or orthostasis at therapeutic doses. 6