Therapeutic Dose of Fluoxetine
For major depressive disorder in adults, start fluoxetine at 20 mg once daily in the morning, which is sufficient for most patients; doses above 20 mg/day may be considered after several weeks if insufficient clinical improvement is observed, with a maximum of 80 mg/day. 1
Initial Dosing for Depression
Adult Patients:
- Start at 20 mg once daily in the morning 1
- Studies demonstrate that 20 mg/day is sufficient to obtain satisfactory response in major depressive disorder in most cases 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
- Full therapeutic effect may be delayed until 4 weeks of treatment or longer 1
Pediatric Patients (children and adolescents):
- Start at 10 mg/day for lower weight children, or 10-20 mg/day for others 2
- After 1 week at 10 mg/day, increase to 20 mg/day 2
- The starting and target dose for lower weight children may remain at 10 mg/day 2
- Effective dose: 20 mg/day; Maximum: 60 mg/day 2
Therapeutic Drug Monitoring Range
The recommended therapeutic plasma concentration range for fluoxetine plus norfluoxetine is 120-300 ng/mL (Level of recommendation: 3) 2. This represents combined parent drug and active metabolite concentrations at steady state.
Dosing for Obsessive-Compulsive Disorder
For OCD, higher doses are required:
- Effective dose range: 40-60 mg daily 3
- Maximum dose: 60-80 mg daily 4
- Higher SSRI dosing for OCD is associated with greater efficacy, though also higher dropout rates due to adverse effects 4
- Efficacy should not be evaluated before 8 weeks to allow for onset of therapeutic effects 3
- Minimum treatment duration: 1-2 years 3
Special Dosing Considerations
Low-Dose Strategy:
- Some patients, particularly those with panic disorder, may be intolerant of the standard 20 mg/day dose 5
- Starting at 5 mg/day and gradually increasing to 20 mg/day over 1 week may be beneficial 5
- Approximately 28% of patients may be unable to tolerate the full 20 mg dose but can benefit from lower doses 5
Hepatic Impairment:
- Use lower or less frequent dosage in patients with hepatic impairment 1
Elderly Patients:
- Consider lower or less frequent dosage 1
CYP2D6 Poor Metabolizers:
- CYP2D6 poor metabolizers have 3.9-fold higher drug exposure at 20 mg and 11.5-fold higher exposure at 60 mg compared to extensive metabolizers 4
- Consider genetic testing before initiating high-dose therapy in patients with known CYP2D6 poor metabolizer status 4
- FDA has issued warnings about QT prolongation risk in CYP2D6 poor metabolizers 4
Maintenance Treatment
Duration:
- Acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy 1
- Efficacy is maintained for periods of up to 38 weeks following 12 weeks of acute treatment at 20 mg/day 1
- For first episode of major depressive disorder, continue treatment for 4-12 months after remission 6
Weekly Dosing Option:
- Prozac Weekly capsules may be initiated 7 days after the last daily dose of Prozac 20 mg 1
- If satisfactory response is not maintained with weekly dosing, consider reestablishing daily dosing 1
Common Pitfalls and Monitoring
Adverse Effects:
- Most common: insomnia, asthenia, somnolence, nausea, anxiety, anorexia, diarrhea, nervousness, headache, decreased libido 7, 8
- Adverse events leading to discontinuation occur at similar rates to placebo (6.1% vs 5.8%) at 20 mg/day 7
- Nervousness or insomnia at treatment start may predict good response 3
Drug Interactions:
- Fluoxetine is a potent CYP2D6 inhibitor, creating significant drug-drug interactions with medications metabolized by CYP2D6 4
- Fluoxetine converts approximately 43% of extensive metabolizers to poor metabolizer phenotype during chronic use 4
- 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 1
Discontinuation:
- Taper gradually over 10-14 days to limit withdrawal symptoms 6