What are the recommended dosing and titration increments for Prozac (fluoxetine)?

Prozac (Fluoxetine) Dosing and Titration

For most adults with depression, start fluoxetine at 10 mg daily (or 10 mg every other morning) and increase to 20 mg daily after 1-2 weeks, with subsequent dose adjustments at 3-4 week intervals using 5-10 mg increments due to the exceptionally long half-life of fluoxetine and its active metabolite. 1, 2

Initial Dosing Strategy

Standard Adult Dosing

• Begin with 10 mg daily in the morning (or 10 mg every other morning for highly sensitive patients) 1
• Morning dosing is essential because fluoxetine is activating and causes insomnia if taken later in the day 1
• After 1 week for panic disorder or 1-2 weeks for depression/OCD, increase to 20 mg daily 2

Special Considerations for Anxiety-Prone Patients

• Use a subtherapeutic "test dose" strategy when anxiety is a concern, starting even lower than 10 mg 1
• Patients with panic disorder are particularly intolerant of standard 20 mg starting doses and may require slower titration 3
• Research shows 28% of patients cannot tolerate the full 20 mg dose, with half of these discontinuing entirely—most having comorbid panic disorder 3

Titration Intervals and Increments

Critical Timing Considerations

• Increase doses at 3-4 week intervals, NOT 1-2 weeks, due to fluoxetine's extraordinarily long half-life 1
• Fluoxetine has a 1-3 day half-life, but its active metabolite norfluoxetine has a 4-16 day half-life 1, 4
• Side effects may not manifest for several weeks after dose changes because steady-state takes weeks to achieve 1

Increment Size

• Use the smallest available increments of 5-10 mg when titrating upward 1
• For OCD in adolescents and higher-weight children: start 10 mg daily, increase to 20 mg after 2 weeks, then consider additional increases after several more weeks 2
• For lower-weight children with OCD: start 10 mg daily with slower subsequent increases 2

Target and Maximum Doses

Therapeutic Ranges by Indication

• Depression: 20-40 mg daily is optimal; maximum 80 mg daily 2, 4
• OCD: 20-60 mg daily recommended; maximum 80 mg daily 2
• Bulimia nervosa: 60 mg daily is the only dose proven superior to placebo; titrate up over several days 2
• Panic disorder: 20 mg daily most frequently used; maximum 60 mg daily studied 2

Important Dosing Caveat

• Higher doses are associated with more adverse effects without clear evidence of superior efficacy 1
• Doses above 60-80 mg daily have minimal supporting data and significantly increased side effect burden 2, 5

Management of Dose-Related Adverse Effects

If Anxiety or Agitation Worsens After Dose Increase

• Immediately reduce back to the previous tolerated dose (e.g., return to 20 mg if 30 mg caused problems) 1
• Increased anxiety and agitation are recognized initial adverse effects of SSRIs that worsen with dose escalation 1
• Wait a full 3-4 weeks at the tolerated dose before attempting another increase 1

Alternative to Dose Escalation

• Consider adding CBT to the current tolerated fluoxetine dose rather than increasing medication, as combination therapy shows superior outcomes to medication alone for anxiety disorders 1

Special Populations

Hepatic Impairment and Elderly

• Use lower or less frequent dosing in patients with hepatic impairment 2
• Consider lower or less frequent dosing for elderly patients 2
• Renal impairment does not require routine dosage adjustments 2

Pharmacogenetic Considerations

• If anxiety persists despite dose adjustments, consider CYP2D6 testing, as poor metabolizers have 3.9 to 11.5-fold higher fluoxetine levels and can reach toxic levels at standard doses 1

Monitoring Requirements

• Assess anxiety symptoms systematically using standardized rating scales 1
• Monitor weekly during dose adjustments 1
• Watch for suicidal thinking, especially in the first months and after dose changes 1
• Monitor for behavioral activation, hypomania, mania, seizures, abnormal bleeding, and serotonin syndrome 1

Maintenance and Discontinuation

Duration of Treatment

• OCD and panic disorder are chronic conditions; continuation is reasonable for responding patients 2
• Periodically reassess to determine ongoing need for treatment 2

Discontinuation Strategy

• Fluoxetine's long half-life essentially precludes withdrawal phenomena, making it unique among SSRIs 5
• Tapering may be considered in the third trimester of pregnancy 2
• Unlike shorter half-life SSRIs (which require 10-14 day tapers), fluoxetine can often be stopped without gradual tapering due to its self-tapering pharmacokinetics 5