Prozac (Fluoxetine) Dosing for Depression and Anxiety
Standard Adult Dosing
Start fluoxetine at 20 mg once daily in the morning for most adults with depression or anxiety. 1 This is the FDA-approved initial dose and is sufficient to obtain a satisfactory response in major depressive disorder in most cases. 1
Initial Dosing Strategy
For patients with prominent anxiety symptoms or panic disorder, consider starting at 10 mg daily (or even 5 mg daily) for the first week before increasing to 20 mg daily. 2 Approximately 28% of patients cannot tolerate the full 20 mg dose initially, with half of these patients doing well clinically on lower doses. 2
Morning dosing is strongly preferred because fluoxetine is activating and may cause insomnia if taken later in the day. 3
Dose Titration
If insufficient clinical improvement occurs after several weeks at 20 mg daily, increase the dose in increments. 1 The FDA label supports doses up to 80 mg/day for depression and anxiety disorders. 1
For OCD specifically, higher doses (60-80 mg daily) demonstrate superior efficacy compared to lower doses and are often necessary. 4
Allow 4 weeks or longer for full therapeutic effect before concluding treatment failure. 1
Dosing Schedules
Doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon). 1
Maximum dose should not exceed 80 mg/day. 1
Special Populations
Elderly Patients
Use lower or less frequent dosing in elderly patients—approximately 50% of the standard adult starting dose. 3 Older adults are at significantly greater risk of adverse drug reactions. 3
Hepatic Impairment
A lower or less frequent dosage should be used in patients with hepatic impairment. 1
CYP2D6 Poor Metabolizers
CYP2D6 poor metabolizers should start at 10 mg daily with cautious titration due to 3.9 to 11.5-fold higher fluoxetine levels and significantly increased toxicity risk, including QT prolongation. 3 The FDA has issued safety warnings about this risk. 3
Pediatric Dosing (Children and Adolescents)
Start with 10 mg daily for one week, then increase to 20 mg daily. 1 In lower weight children, the starting and target dose may remain at 10 mg/day, with dose increases to 20 mg considered after several weeks if insufficient improvement occurs. 1
Treatment Duration
Continue fluoxetine for 4-9 months minimum after satisfactory response for first-episode depression. 4 For patients with recurrent episodes, consider longer duration of ≥1 year or indefinite maintenance therapy. 4
Critical Safety Monitoring
Monitor closely for treatment-emergent suicidality, particularly in the first 1-2 weeks after initiation or dose changes, especially in patients under age 24. 4 All SSRIs carry FDA black box warnings for increased suicidality risk. 4
Fluoxetine has an exceptionally long half-life (1-3 days for parent compound, 4-16 days for active metabolite norfluoxetine), meaning steady-state is not reached until approximately 5-7 weeks after a dose change. 3 Side effects may not manifest for several weeks. 3
Common Pitfalls to Avoid
Do not discontinue prematurely—full response may take 6-8 weeks, and approximately 38% of patients do not achieve response during initial 6-12 weeks. 4
Do not combine with MAOIs due to serotonin syndrome risk. Allow at least 14 days after stopping an MAOI before starting fluoxetine, and at least 5 weeks after stopping fluoxetine before starting an MAOI. 1
Fluoxetine strongly inhibits CYP2D6 and can cause dangerous interactions with tamoxifen, codeine, tramadol, and other CYP2D6 substrates. 4
Gradual tapering is recommended when discontinuing, although fluoxetine has the lowest risk of discontinuation syndrome among SSRIs due to its long half-life. 4
Comparative Efficacy
Fluoxetine demonstrates equivalent efficacy to other SSRIs (sertraline, paroxetine, escitalopram, citalopram) for treating depression and anxiety. 4 However, venlafaxine may have statistically better response rates than fluoxetine specifically for depression with prominent anxiety symptoms. 4
Fluoxetine is effective in treating major depression with comorbid anxiety disorders, with significant effects on both depression and anxiety symptoms. 5, 6, 7 In one study, 53% of patients with depression and comorbid anxiety disorders were responders (≥50% decrease in depression scores) after 8 weeks of fluoxetine 20 mg daily. 5