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

Fluoxetine Dosing Recommendations

For most adults with depression, start fluoxetine at 10 mg daily (or 10 mg every other morning) and increase to the standard therapeutic dose of 20 mg/day after 1-2 weeks, with morning administration preferred to minimize insomnia. 1, 2

Initial Dosing Strategy

Standard Adult Dosing

• Begin with 10 mg daily in the morning (or 10 mg every other morning for particularly sensitive patients) 1
• After 1 week, increase to 20 mg/day as the standard therapeutic dose 3
• Morning dosing is essential because fluoxetine is activating and causes insomnia if taken later in the day 1, 4

Indication-Specific Dosing

Major Depressive Disorder:

• Standard dose: 20 mg/day 3, 5
• Dose range: 20-80 mg/day (maximum 80 mg/day) 3
• The 20 mg/day dose demonstrates significant efficacy with lower adverse event rates compared to higher doses 5

Panic Disorder:

• Start at 10 mg/day for 1 week, then increase to 20 mg/day 3
• Most patients respond to 20 mg/day 3
• Patients with panic disorder are particularly sensitive to initial activation and may require slower titration 6

OCD:

• Adults: Start 20 mg/day, titrate to 60 mg/day for optimal response 3
• Adolescents/higher weight children: Start 10 mg/day for 2 weeks, then 20 mg/day, with target range 20-60 mg/day 3
• Lower weight children: Start 10 mg/day, target range 20-30 mg/day 3

Bulimia Nervosa:

• 60 mg/day administered in the morning is the only dose proven effective 3
• Titrate up to this target dose over several days if needed 3

Dose Titration Principles

Critical Timing Considerations

• Wait 3-4 weeks at each new dose before further adjustments due to fluoxetine's exceptionally long half-life (1-3 days for parent compound, 4-16 days for active metabolite norfluoxetine) 1, 2
• Side effects may not manifest for several weeks after starting or increasing the dose 1, 4
• Assess treatment response using standardized symptom scales after 4-6 weeks at a new dose 2

Dose Escalation Strategy

• Use the smallest available increments (5-10 mg increases) when titrating 1
• If anxiety or agitation develops after dose increase, immediately reduce back to the previous tolerated dose 1
• Higher doses are associated with more adverse effects without clear evidence of superior efficacy for most indications 1

Special Populations

Patients with Anxiety or Panic Features

• Consider starting with 5 mg/day as a "test dose" strategy 1, 6
• 28% of patients cannot tolerate the full 20 mg dose, with half of these responding well to lower doses 6
• Patients with concurrent panic disorder are particularly intolerant of standard starting doses 6

Elderly and Dementia Patients

• Start with 10 mg every other morning, maximum 20 mg every morning 2, 3
• Use lower or less frequent dosing 3

Hepatic Impairment

• Use lower or less frequent dosing 3

CYP2D6 Poor Metabolizers

• Exercise extreme caution: poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels 1
• Significantly increased risk of toxicity, QT prolongation, and elevated drug levels even at standard doses 1, 4
• Consider CYP2D6 testing if anxiety or side effects persist despite dose adjustments 1

Monitoring Requirements

Early Monitoring (First 24-48 Hours)

• Assess for behavioral activation/agitation, restlessness, insomnia, impulsiveness, and increased anxiety 2

Ongoing Monitoring

• Weekly assessments during dose adjustments using standardized rating scales 1
• Monitor systematically for anxiety symptoms 1

Common Pitfalls to Avoid

• Do not increase doses at 1-2 week intervals—the long half-life requires 3-4 weeks between adjustments 1
• Do not dose in the evening—this causes insomnia due to activating properties 1, 4
• Do not assume immediate side effects—adverse effects can develop over several weeks due to the long half-life 1, 4
• Do not push to higher doses prematurely—consider adding CBT to current tolerated dose rather than escalating medication, as combination therapy shows superior outcomes 1

Alternative Dosing Schedules

• Due to the extremely long half-life, every-third-day dosing with 20 mg may be effective after initial 4 weeks of daily dosing, though daily dosing at 40 mg shows reduced relapse rates 7
• Renal impairment does not require routine dosage adjustments 3