What is the recommended dosing of Prozac (fluoxetine) for an adult patient with depression or anxiety?

Fluoxetine (Prozac) Dosing for Depression and Anxiety

Standard Adult Dosing for Depression

For major depressive disorder in adults, start fluoxetine at 20 mg once daily in the morning, as this dose is sufficient to obtain a satisfactory response in most cases. 1

• The FDA-approved initial dose is 20 mg/day administered in the morning 1
• Doses above 20 mg/day may be administered once daily (morning) or twice daily (morning and noon), with a maximum of 80 mg/day 1
• A dose increase may be considered after several weeks if insufficient clinical improvement is observed 1
• The full antidepressant effect may be delayed until 4 weeks of treatment or longer 1

Alternative Low-Dose Initiation Strategy

For patients with anxiety disorders or those prone to activation side effects, start at 10 mg daily (or even 5-10 mg every other morning) and titrate slowly to 20 mg over 1-2 weeks. 2, 3

• Starting at 10 mg daily is particularly appropriate for patients with concurrent panic disorder, as 28% of patients cannot tolerate the full 20 mg dose initially 3
• Fluoxetine is activating and may cause insomnia if taken later in the day; morning dosing is strongly preferred 2
• Due to fluoxetine's very long half-life (1-3 days for fluoxetine, 4-16 days for norfluoxetine), side effects may not manifest for several weeks after dose changes 2

Pediatric Dosing (Children and Adolescents)

Initiate treatment in pediatric patients at 10 mg/day, then increase to 20 mg/day after 1 week. 1

• In lower weight children, both the starting and target dose may remain at 10 mg/day due to higher plasma levels 1
• After several weeks at 10 mg/day, consider increasing to 20 mg/day if insufficient clinical improvement is observed 1

Dosing for Panic Disorder and Anxiety

For panic disorder, start at 10 mg daily for 1 week, then increase to 20 mg daily, as this gradual titration improves tolerability. 4

• Fluoxetine 20 mg daily is safe and efficacious in reducing panic symptoms after 6 weeks 4
• Patients who fail to obtain satisfactory response at 20 mg daily may benefit from dose increases up to 60 mg daily 4
• Once panic-free on daily dosing, some patients can be maintained on once-weekly dosing (10-60 mg weekly) for up to 26 months 5

Maintenance Treatment

Continue fluoxetine at the dose that induced remission for at least 4-6 months (or longer) to prevent relapse. 1

• Efficacy in major depressive disorder is maintained for up to 38 weeks following acute treatment at 20 mg/day 1, 2
• Weekly dosing with Prozac Weekly (90 mg once weekly) can be initiated 7 days after the last daily 20 mg dose for maintenance therapy 1
• If satisfactory response is not maintained with weekly dosing, reestablish a daily dosing regimen 1

Special Populations

Elderly Patients

Use lower or less frequent dosing in elderly patients—start at approximately 50% of the standard adult dose (10 mg daily). 2

• Older adults are at significantly greater risk of adverse drug reactions 2
• Fluoxetine should generally be avoided in older adults due to higher rates of adverse effects, very long half-life, and extensive CYP2D6 interactions 6
• Sertraline and escitalopram are preferred alternatives in elderly patients 6

Hepatic Impairment

A lower or less frequent dosage should be used in patients with hepatic impairment. 1

CYP2D6 Poor Metabolizers

Start at 10 mg daily with cautious titration in CYP2D6 poor metabolizers, as they have 3.9 to 11.5-fold higher fluoxetine levels and significantly increased toxicity risk. 2

• Single-dose fluoxetine at 20 mg produces 3.9-fold higher drug exposure in poor metabolizers 2
• At 60 mg, drug exposure is 11.5-fold higher in poor metabolizers 2
• The FDA has issued safety warnings about QT prolongation risk in CYP2D6 poor metabolizers 2
• Consider CYP2D6 testing if unexpected adverse effects develop at standard doses 2

Dose Titration Guidelines

When increasing fluoxetine dose, wait 3-4 weeks between increments due to the exceptionally long half-life, not the typical 1-2 weeks used for shorter half-life SSRIs. 2

• Steady-state plasma concentrations are not reached until approximately 5-7 weeks after a dose change 2
• Use the smallest available increments (5-10 mg increases) when titrating 2
• Higher SSRI doses are associated with increased dropout rates due to adverse effects, particularly during the first few weeks when plasma levels are still rising 2

Common Pitfalls to Avoid

• Never increase fluoxetine dose rapidly in patients with anxiety, as increased anxiety and agitation are recognized initial adverse effects that worsen with dose escalation 2
• Do not discontinue fluoxetine abruptly—taper gradually over 10-14 days to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 6
• Avoid fluoxetine in patients taking multiple medications due to potent CYP2D6 inhibition, which converts approximately 43% of extensive metabolizers to poor metabolizer phenotype during chronic use 2
• Do not combine fluoxetine with MAOIs due to risk of serotonin syndrome 6

Monitoring Requirements

• Assess treatment response at 4 weeks and 8 weeks using standardized rating scales 2
• Monitor for behavioral activation, anxiety, or agitation, especially in the first 2-4 weeks 2, 7
• Screen for suicidal thinking, particularly in patients under age 24 2
• If symptoms are stable or worsening after 8 weeks despite good adherence, adjust the regimen by switching medications or adding CBT 2