Prozac (Fluoxetine) Therapeutic Dose
For adults with major depressive disorder, start with 20 mg daily in the morning, which is sufficient for most patients, with a maximum dose of 80 mg/day if needed after several weeks of inadequate response. 1
Initial Dosing Strategy
- Start with 20 mg once daily in the morning as the FDA-approved initial dose for major depressive disorder in adults 1
- If anxiety or agitation is a concern, consider starting with a subtherapeutic "test dose" of 10 mg daily (or 10 mg every other morning), then increase slowly due to fluoxetine's activating properties 2, 3
- Morning dosing is preferred because fluoxetine is activating and may cause insomnia if taken later in the day 2
Dose Escalation
- A dose increase may be considered after several weeks if insufficient clinical improvement is observed, but 20 mg/day is sufficient to obtain a satisfactory response in most cases 1
- Doses above 20 mg/day can be administered once daily (morning) or twice daily (morning and noon), with a maximum of 80 mg/day 1
- Increase doses at 3-4 week intervals, not 1-2 weeks, using the smallest available increments (5-10 mg increases) due to fluoxetine's exceptionally long half-life 2
- The full therapeutic effect may be delayed until 4 weeks of treatment or longer 1
Pharmacokinetic Considerations
- Fluoxetine has a very long half-life: 1-3 days for the parent compound and 4-16 days for its active metabolite norfluoxetine 2, 4
- Steady-state plasma concentrations are not reached until approximately 5-7 weeks after a dose change, meaning side effects may not manifest for several weeks 2, 3
- This long half-life makes fluoxetine essentially free from withdrawal phenomena 5
Special Populations and Genetic Considerations
- CYP2D6 poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and are at significantly higher risk of toxicity even at standard doses 2
- Start at 10 mg daily with cautious titration in known CYP2D6 poor metabolizers 2
- Consider CYP2D6 genetic testing if patients develop unexpected adverse effects or unusual sensitivity to standard doses 2, 3
- The FDA has issued safety warnings about QT prolongation risk in CYP2D6 poor metabolizers 2, 3
- Use lower or less frequent dosing in elderly patients (approximately 50% of standard adult starting dose) as they are at significantly greater risk of adverse drug reactions 2, 1
- Lower or less frequent dosage should be used in patients with hepatic impairment 1
Condition-Specific Dosing
- For OCD, higher doses (40-60 mg daily) are generally necessary and more effective than lower doses, with efficacy maintained over long-term treatment 2, 6
- For panic disorder, doses up to 60 mg daily may be needed for inadequate responders 2
Maintenance Treatment
- Continue treatment for 4-12 months after first episode of major depressive disorder 3
- Efficacy is maintained for up to 38 weeks following acute treatment at 20 mg/day 2, 1
- For recurrent depression, prolonged treatment may be beneficial 3
Critical Safety Warnings
- Higher doses are associated with more adverse effects and higher dropout rates without clear evidence of superior efficacy for depression 2, 5
- Monitor for increased anxiety and agitation, particularly during dose escalation, as these are recognized initial adverse effects 2
- Fluoxetine is a potent CYP2D6 inhibitor that converts approximately 43% of extensive metabolizers to poor metabolizer phenotype during chronic use, increasing drug interaction risks 2, 3
- Exercise caution when combining with other serotonergic drugs due to risk of serotonin syndrome 3
- Use with caution in patients with congenital long QT syndrome, family history of sudden cardiac death, or conditions predisposing to QT prolongation 3