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 this intolerance being particularly common in patients with comorbid panic disorder. 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, though doses above 20 mg may be administered once daily (morning) or twice daily (morning and noon). 1
For OCD specifically, higher doses (60-80 mg daily) demonstrate superior efficacy compared to lower doses and are often necessary. 4 The dose range of 20-60 mg/day is recommended for OCD, with doses up to 80 mg/day being well tolerated. 1
Allow 3-4 weeks between dose increases due to fluoxetine's exceptionally long half-life (1-3 days for fluoxetine, 4-16 days for active metabolite norfluoxetine). 3 Steady-state plasma concentrations are not reached until approximately 5-7 weeks after a dose change. 3
Expected Timeline
The full therapeutic effect may be delayed until 4-5 weeks of treatment or longer. 1 For OCD, the full effect may take 5 weeks or more. 1
Assess treatment response at 4 weeks and 8 weeks using standardized symptom rating scales. 4
Special Populations and Safety Considerations
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
Patients with Hepatic Impairment
- A lower or less frequent dosage should be used in patients with hepatic impairment. 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 starting at 10 mg daily with cautious titration in known poor metabolizers. 3
If unexpected adverse effects develop at standard doses, consider CYP2D6 genetic testing. 3 The FDA has issued safety warnings about QT prolongation risk in CYP2D6 poor metabolizers. 4, 3
Critical Safety Monitoring
Monitor closely for treatment-emergent suicidality, particularly in the first 1-2 weeks after initiation or dose changes. 4 All SSRIs carry FDA black box warnings for increased suicidality risk, especially in patients under age 24. 4
Initial adverse effects can include anxiety or agitation, which typically resolve with continued treatment. 4 If anxiety worsens after a dose increase, reduce back to the previous tolerated dose immediately. 3
Never combine fluoxetine with MAOIs due to serotonin syndrome risk. 4 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
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 (≥1 year or indefinite maintenance therapy). 4
Fluoxetine efficacy is maintained for up to 38 weeks following acute treatment at 20 mg/day. 1
Common Pitfalls to Avoid
Do not increase doses too rapidly. Due to the long half-life, side effects may not manifest for several weeks after dose changes. 3
Do not discontinue abruptly. Although fluoxetine has the lowest risk of discontinuation syndrome among SSRIs due to its long half-life, gradual tapering is still recommended when stopping. 4
Be aware of significant drug interactions. Fluoxetine strongly inhibits CYP2D6 and can cause dangerous interactions with tamoxifen, codeine, tramadol, and other CYP2D6 substrates. 4
Efficacy in Depression with Anxiety
Fluoxetine is effective for treating major depression with comorbid anxiety disorders, with significant effects on both depression and anxiety symptoms. 5, 6 In patients with major depression and comorbid anxiety, fluoxetine reduces anxiety by 55% and depression by 60%. 4 The presence of anxiety does not affect response to fluoxetine. 7