Fluoxetine (Prozac) Dosing
Standard Dosing for Major Depressive Disorder
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
Initial Dosing Strategy
- Adults: The FDA-approved starting dose is 20 mg once daily in the morning 1
- Pediatric patients (children and adolescents): Start with 10 mg daily for one week, then increase to 20 mg daily 1
- Lower weight children: May remain at 10 mg daily as the target dose due to higher plasma levels 1
Alternative Low-Dose Initiation
- For patients with anxiety disorders or panic disorder, consider starting at 5-10 mg daily (or 10 mg every other morning) and gradually titrating up over 1 week, as 28% of patients cannot tolerate the full 20 mg dose but may benefit from lower doses 2, 3
- This "test dose" strategy is particularly important when anxiety is a concern, as fluoxetine is activating and can worsen anxiety symptoms initially 2
Dose Escalation
Timing and Increments
- If insufficient clinical improvement after several weeks at 20 mg, consider dose escalation 1
- Increase doses at 3-4 week intervals (not 1-2 weeks) due to fluoxetine's extremely long half-life (1-3 days for fluoxetine, 4-16 days for norfluoxetine) 2, 4
- Use the smallest available increments of 5-10 mg when increasing 2
Dose Range
- Doses above 20 mg may be administered once daily (morning) or twice daily (morning and noon) 1
- Maximum dose: 80 mg/day 1
- Studies show that 20 mg/day is sufficient for most patients, though doses of 20-60 mg have been used in clinical trials 5, 1
Maintenance Treatment
Daily Dosing
- Continue the effective dose (typically 20 mg/day) for several months or longer, as acute episodes require sustained pharmacologic therapy 1
- Efficacy is maintained for up to 38 weeks following acute treatment at 20 mg/day 1
Weekly Dosing Option
- Fluoxetine Weekly (90 mg once weekly) is available for maintenance treatment after stabilization on daily dosing 1
- Initiate weekly dosing 7 days after the last daily 20 mg dose 1
- Weekly dosing shows superior compliance (87.8%) compared to daily dosing (79.0%) during continuation treatment 6
- If response is not maintained with weekly dosing, reestablish daily dosing 1
Special Populations
Hepatic or Renal Impairment
- Use a lower or less frequent dosage in patients with hepatic impairment 1
- Dosage adjustments for renal impairment are not routinely necessary 1
Elderly Patients
- Consider lower or less frequent dosing 1
- In elderly patients with Alzheimer's disease and depression, maximum recommended dose is only 20 mg daily 7
CYP2D6 Poor Metabolizers
- Exercise extreme caution: Poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and are at significantly higher risk of toxicity, including QT prolongation, even at standard doses 2, 7
- Consider CYP2D6 testing if anxiety or adverse effects persist despite dose adjustments 2
Important Pharmacokinetic Considerations
- Onset of full effect may be delayed 4 weeks or longer 1
- The very long half-life means side effects may not manifest for several weeks after starting or dose changes 2, 4
- Morning dosing is preferred as fluoxetine is activating and may cause insomnia if taken later in the day 2
- At least 5 weeks should elapse after stopping fluoxetine before starting an MAOI due to the long half-life 1
Common Pitfalls to Avoid
- Don't escalate doses too rapidly: The long half-life means steady-state is not reached for weeks, so effects of dose changes are delayed 2, 7
- Don't ignore increased anxiety with dose escalation: This is a recognized adverse effect that warrants dose reduction back to the previously tolerated level 2
- Don't assume higher doses are always better: Higher doses are associated with more adverse effects and increased dropout rates without clear evidence of superior efficacy 2, 8
- Consider adding CBT to the current tolerated dose rather than escalating medication, as combination therapy shows superior outcomes 2