Fluoxetine (Prozac) Dosing Guidelines
For adults with major depressive disorder, start fluoxetine at 20 mg once daily in the morning, as this dose is sufficient to obtain a satisfactory response in most cases. 1
Adult Dosing 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 can be given 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
Obsessive-Compulsive Disorder (OCD)
- Initial dose: 20 mg once daily in the morning 1
- Target dose range: 20-60 mg/day, though doses up to 80 mg/day have been well tolerated 1
- Dose increases may be considered after several weeks if insufficient improvement is observed 1
- Full therapeutic effect may be delayed until 5 weeks or longer 1
- Maximum dose should not exceed 80 mg/day 1
Panic Disorder
- Initial dose: 10 mg/day for 1 week, then increase to 20 mg/day 1
- The most frequently administered dose in clinical trials was 20 mg/day 1
- Dose increases may be considered after several weeks if no clinical improvement is observed 1
- Doses above 60 mg/day have not been systematically evaluated 1
Bulimia Nervosa
- Recommended dose: 60 mg/day administered in the morning 1
- For some patients, titration up to this target dose over several days may be advisable 1
- Only the 60 mg dose was statistically superior to placebo in reducing binge-eating and vomiting frequency 1
Pediatric Dosing (Children and Adolescents)
Major Depressive Disorder
- Initial dose: 10 or 20 mg/day 1
- After 1 week at 10 mg/day, increase to 20 mg/day 1
- In lower weight children, the starting and target dose may be 10 mg/day 1
- A dose increase to 20 mg/day may be considered after several weeks if insufficient improvement is observed 1
Obsessive-Compulsive Disorder
- Adolescents and higher weight children: Start with 10 mg/day, increase to 20 mg/day after 2 weeks 1
- Recommended dose range: 20-60 mg/day 1
- Lower weight children: Start with 10 mg/day 1
- Recommended dose range for lower weight children: 20-30 mg/day 1
- Experience with doses greater than 20 mg is very minimal in this population 1
Critical Titration Considerations
Fluoxetine's Unique Pharmacokinetics
- Fluoxetine has a very long half-life: 1-3 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine 2
- Due to this long half-life, dose increases should occur at 3-4 week intervals, not 1-2 weeks 3, 2
- Side effects may not manifest for several weeks after starting or changing doses 2
- The long half-life essentially precludes a withdrawal phenomenon 4
Managing Anxiety and Agitation
- Initial adverse effects of SSRIs can include anxiety or agitation 3
- Consider starting with a subtherapeutic "test" dose when anxiety is a concern 3, 2
- If increased anxiety occurs after dose escalation, immediately reduce back to the previous tolerated dose 2
- Use the smallest available increments (5-10 mg increases) when titrating 2
- Higher doses are associated with more adverse effects without clear evidence of superior efficacy 3, 2
Maintenance Treatment
Major Depressive Disorder
- Daily dosing: Efficacy maintained for up to 38 weeks at 20 mg/day 1
- Weekly dosing option: Prozac Weekly (90 mg capsule) can be initiated 7 days after the last daily 20 mg dose 1
- If satisfactory response is not maintained with weekly dosing, reestablish daily dosing regimen 1
OCD and Panic Disorder
- These are chronic conditions; continuation for responding patients is reasonable 1
- Patients should be periodically reassessed to determine need for continued treatment 1
Bulimia Nervosa
- Continuing 60 mg/day for up to 52 weeks has demonstrated maintenance benefit 1
Special Populations and Dose Adjustments
Hepatic Impairment
- A lower or less frequent dosage should be used 1
Elderly Patients
- Consider lower or less frequent dosing 1
Renal Impairment
- Dosage adjustments are not routinely necessary 1
CYP2D6 Poor Metabolizers
- Poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels 2
- These patients are at significantly higher risk of toxicity, including QT prolongation, even at standard doses 2
- Consider CYP2D6 testing if anxiety persists despite dose adjustments or if toxicity is suspected 2
Important Drug Interactions and Contraindications
MAOIs
- At least 14 days must elapse between discontinuing an MAOI and starting fluoxetine 1
- At least 5 weeks (perhaps longer) must elapse after stopping fluoxetine before starting an MAOI 1
- This extended washout period is necessary due to fluoxetine's long half-life 1
Serotonin Syndrome Risk
- Avoid combining with other serotonergic drugs, especially MAOIs 3
- Exercise caution when combining two or more non-MAOI serotonergic drugs 3
- When adding a second serotonergic drug, start at low dose, increase slowly, and monitor for symptoms in the first 24-48 hours after dosage changes 3
CYP450 Interactions
- Fluoxetine inhibits CYP2D6 and other CYP enzymes 3, 4
- May interact with drugs metabolized by CYP2D6 3
- Citalopram/escitalopram may have lower propensity for drug interactions compared to fluoxetine 3
Practical Dosing Strategy
For Patients with Anxiety Disorders
- Consider adding CBT to the current tolerated fluoxetine dose rather than increasing medication, as combination therapy shows superior outcomes to medication alone 2
- Start with 10 mg/day as a test dose if anxiety is a primary concern 5
- 28% of patients may be unable to tolerate the full 20 mg dose, but many benefit from lower doses 5
- Patients with panic disorder are particularly likely to be intolerant of standard doses 5