Starting Dose for Fluoxetine
For adults with depression or anxiety disorders, start fluoxetine at 20 mg once daily in the morning, as this is the FDA-approved initial dose that provides optimal efficacy with acceptable tolerability in most patients. 1
Standard Adult Dosing
The FDA-approved starting dose is 20 mg/day administered in the morning for major depressive disorder, as controlled trials demonstrate this dose is sufficient to obtain a satisfactory response in most cases 1
Studies comparing 20,40, and 60 mg/day to placebo confirm that 20 mg/day achieves adequate efficacy without requiring higher initial doses 1
The full therapeutic effect may be delayed until 4 weeks of treatment or longer, so patience is required before considering dose escalation 1
Alternative Low-Dose Strategy for Specific Populations
Consider starting at 10 mg daily (or even 10 mg every other morning) in patients who may be particularly sensitive to side effects, including those with:
Panic disorder or prominent anxiety symptoms, as 28% of patients in one study could not tolerate the standard 20 mg dose, with panic disorder patients being particularly intolerant 2
Lower body weight or elderly patients, who may experience higher plasma concentrations 3, 1
Known or suspected CYP2D6 poor metabolizer status, as these individuals have 3.9 to 11.5-fold higher fluoxetine levels and significantly increased toxicity risk even at standard doses 3
Dosing Rationale and Pharmacokinetics
Fluoxetine has an exceptionally long half-life of 1-3 days for the parent compound and 4-16 days for its active metabolite norfluoxetine, meaning steady-state is not reached for approximately 5-7 weeks 3
This long half-life permits once-daily dosing and means side effects may not manifest for several weeks after initiation 3
Morning dosing is preferred because fluoxetine is activating and may cause insomnia if taken later in the day 3
Dose Escalation Considerations
If insufficient clinical improvement occurs after several weeks at 20 mg/day, doses may be increased, but should not exceed 80 mg/day 1
Doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon) 1
Due to fluoxetine's long half-life, allow at least 3-4 weeks between dose increases to reach steady-state and accurately assess response 3
Common Pitfalls to Avoid
Do not rush dose escalation - the long half-life means plasma levels continue rising for weeks, and premature increases can lead to cumulative adverse effects 3
Monitor closely for behavioral activation/agitation, particularly in younger patients and those with anxiety disorders, as this can occur early in treatment or with dose increases 4
Be vigilant for suicidal ideation, especially in the first months of treatment and following dose adjustments, as all SSRIs carry a boxed warning for this risk through age 24 4
If unexpected adverse effects develop at standard doses, consider CYP2D6 genetic testing, as poor metabolizers may require substantially lower doses 3
Special Population Adjustments
Elderly patients should receive approximately 50% of the standard adult starting dose due to significantly greater risk of adverse drug reactions 3
Patients with hepatic impairment require lower or less frequent dosing 1
Lower weight children and adolescents may start at 10 mg/day as their target dose, with increases to 20 mg/day considered only after several weeks if needed 1