Maximum Dose of Fluoxetine
The maximum recommended dose of fluoxetine is 80 mg/day for major depressive disorder and obsessive-compulsive disorder, and 60 mg/day for bulimia nervosa. 1
Dosing by Indication
Major Depressive Disorder
- Initial dose: 20 mg/day in the morning 1
- Dose escalation: May increase after several weeks if insufficient clinical improvement, administered once daily (morning) or twice daily (morning and noon) 1
- Maximum dose: 80 mg/day 1
- Studies demonstrate that 20 mg/day is sufficient for most patients, though doses up to 80 mg/day have been well tolerated 1, 2
Obsessive-Compulsive Disorder
- Adults: Start at 20 mg/day, with a recommended range of 20-60 mg/day 1
- Maximum dose: 80 mg/day (doses up to 80 mg/day have been well tolerated in open studies) 1
- Pediatric patients (adolescents/higher weight children): Start 10 mg/day, increase to 20 mg/day after 2 weeks, recommended range 20-60 mg/day 1
- Lower weight children: Start 10 mg/day, recommended range 20-30 mg/day 1
Bulimia Nervosa
- Recommended dose: 60 mg/day administered in the morning 1
- This is the only dose proven statistically superior to placebo in reducing binge-eating and vomiting frequency 1
- Maximum studied dose: 60 mg/day (doses above this have not been systematically studied in bulimia) 1
Important Dosing Considerations
Dose-Related Adverse Events
- Common adverse events at the standard 20 mg/day dose include gastrointestinal and nervous system effects 2
- When higher doses are used, adverse events become more common 2
- At 20 mg/day, the incidence of adverse events leading to discontinuation is similar to placebo (6.1% vs 5.8%) 3
Special Populations Requiring Dose Adjustment
- Hepatic impairment: Lower or less frequent dosing should be used 1
- Elderly patients: Consider lower or less frequent dosing 1
- Patients with concurrent disease or multiple medications: Lower or less frequent dosing recommended 1
- Renal impairment: Dosage adjustments are not routinely necessary 1
Clinical Pitfalls
- A substantial fraction of patients (28%) cannot tolerate the standard 20 mg dose, with half of these discontinuing entirely and half doing well on lower doses 4
- Patients with panic disorder in addition to depression are particularly likely to be intolerant of 20 mg/day 4
- Starting at lower doses (5 mg/day) and titrating up may be beneficial for tolerability 4
- Full therapeutic effect may be delayed 4-5 weeks or longer 1
Drug Interactions and Safety
- Fluoxetine inhibits CYP2D6 and other cytochrome P450 enzymes, though most interactions are not clinically important 2
- Monitor for serotonin syndrome when combining with other serotonergic medications 5
- MAOI interactions: At least 14 days must elapse between stopping an MAOI and starting fluoxetine; at least 5 weeks (perhaps longer) must elapse after stopping fluoxetine before starting an MAOI 1