What is the recommended starting dose of fluoxetine (selective serotonin reuptake inhibitor - SSRI)?

Starting Dose of Fluoxetine

The recommended starting dose of fluoxetine is 10 mg once daily in the morning for adolescents, and 20 mg once daily in the morning for adults with major depressive disorder. 1, 2

Adolescent Dosing (Ages 12-17)

• Start with 10 mg once daily for adolescents with depression, as recommended by the American Academy of Pediatrics. 1
• Increase in increments of 10-20 mg based on tolerability and response. 1
• The effective dose range is typically 20 mg daily, with a maximum of 60 mg daily. 1
• Only fluoxetine is FDA-approved for use in children and adolescents with depression among all SSRIs. 1
• Due to fluoxetine's very long half-life (1-3 days for fluoxetine, 4-16 days for norfluoxetine), dose adjustments should occur at 3-4 week intervals, not 1-2 weeks. 3

Critical Safety Consideration for Adolescents

• Never start at higher doses than recommended (i.e., avoid starting above 10 mg in adolescents), as deliberate self-harm and suicide risk are more likely to occur with higher starting doses. 1
• Close monitoring is required, especially during the initial months of treatment and after any dose changes. 1

Adult Dosing

• Start with 20 mg once daily in the morning for adults with major depressive disorder, as this is the FDA-approved initial dose. 2
• Some clinicians may consider starting with 10 mg daily (or even 10 mg every other morning) in patients who are particularly sensitive to medication or have concurrent anxiety/panic disorder. 3, 4
• The 20 mg dose is sufficient for most patients and has been shown to maintain efficacy for up to 38 weeks. 2, 5

When to Consider Lower Starting Doses in Adults

• Patients with panic disorder or significant anxiety may benefit from starting at 5-10 mg daily, as approximately 28% of patients cannot tolerate the full 20 mg dose initially. 4
• CYP2D6 poor metabolizers require cautious dosing due to 3.9 to 11.5-fold higher fluoxetine levels, which can lead to toxicity even at standard doses. 3
• Elderly patients or those with hepatic impairment should start with lower or less frequent dosing. 2

Administration Timing

• Morning dosing is strongly preferred due to fluoxetine's activating properties, which can cause insomnia if taken later in the day. 6, 3
• The very long half-life means side effects may not manifest immediately but can develop over several weeks of treatment. 6, 3

Dose Escalation Strategy

• For adults: If 20 mg is insufficient after several weeks, increase to 40 mg or 60 mg daily. 2
• For adolescents: Increase by 10-20 mg increments after adequate trial at current dose. 1
• Allow 3-4 weeks between dose increases due to the long half-life, as steady-state plasma levels take nearly 4 weeks to achieve. 3, 7
• Maximum recommended dose is 60 mg daily for depression (though up to 80 mg has been used for OCD). 1, 2

Special Populations Requiring Dose Adjustment

• Hepatic impairment: Use lower or less frequent dosing. 2
• Renal impairment: No routine dose adjustment necessary. 2
• Patients with long QT syndrome or family history: Use with extreme caution and consider alternative agents. 6

Common Pitfall to Avoid

The most critical error is starting at doses higher than recommended or escalating too quickly, particularly in adolescents, as this significantly increases the risk of behavioral activation, agitation, and suicidal ideation. 1, 3