Maximum Recommended Dose of Fluoxetine (SSRI)
The maximum recommended dose of fluoxetine is 80 mg per day, though most patients respond adequately to 20-40 mg daily. 1
Dosing Guidelines by Indication
Major Depressive Disorder
- Initial dose: 20 mg once daily in the morning 1
- Dose increases may be considered after several weeks if insufficient clinical improvement is observed 1
- Doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon) 1
- Maximum dose: 80 mg/day 1
Obsessive-Compulsive Disorder
- Initial dose: 20 mg/day in the morning 1
- Dose range: 20-60 mg/day is recommended 1
- Maximum dose: 80 mg/day (well tolerated in open studies) 1
- Pediatric OCD: 10-60 mg/day depending on weight 1
Bulimia Nervosa
- Recommended dose: 60 mg/day 1
- For some patients, titration to target dose over several days may be advisable 1
- Doses above 60 mg/day have not been systematically studied in bulimia 1
Special Considerations
Dosing Frequency
- Daily dosing: Standard approach 1
- Weekly dosing: May be considered for maintenance treatment in some patients after stabilization on daily dosing 1, 2
Special Populations
- Hepatic impairment: Lower or less frequent dosage should be used 1
- Elderly patients: Lower or less frequent dosage should be considered 1
- Patients with concurrent disease or on multiple medications: Lower or less frequent dosage should be considered 1
- Renal impairment: Dosage adjustments not routinely necessary 1
Pharmacokinetic Considerations
- Long half-life: Fluoxetine (1-3 days) and its active metabolite norfluoxetine (4-16 days) 3
- This long elimination half-life essentially precludes withdrawal phenomena 4
- Fluoxetine inhibits cytochrome P450 (CYP) 2D6 and other CYP enzymes, increasing potential for drug interactions 4
Tolerability and Side Effects
- Common adverse events at 20 mg/day primarily affect gastrointestinal and nervous systems 4
- Higher doses (above 20 mg/day) are associated with increased adverse events 4, 5
- Some patients, particularly those with panic disorder, may benefit from starting at lower doses (5 mg/day) with gradual titration 6
- Common side effects include insomnia, asthenia, somnolence, decreased libido, and gastrointestinal disturbances 5
Clinical Pearls
- While doses up to 80 mg/day are approved, most patients respond adequately to 20-40 mg daily 3
- Starting with lower doses (5-10 mg) may improve tolerability, especially in sensitive patients 6
- Full therapeutic effect may be delayed until 4 weeks of treatment or longer 1
- Monitoring for serotonin syndrome is essential when combining with other serotonergic medications 7
Cautions
- At least 14 days should elapse between discontinuation of an MAOI and initiation of fluoxetine 1
- At least 5 weeks should be allowed after stopping fluoxetine before starting an MAOI due to the long half-life 1
- Abrupt discontinuation of shorter-acting SSRIs can lead to discontinuation syndrome, though this is less common with fluoxetine due to its long half-life 7