What is the recommended use and dosage of Fluoxetine (selective serotonin reuptake inhibitor)?

Fluoxetine: Recommended Use and Dosage

Fluoxetine is a first-line selective serotonin reuptake inhibitor (SSRI) indicated for major depressive disorder, obsessive-compulsive disorder, bulimia nervosa, and panic disorder, with dosing that varies significantly by indication—ranging from 20 mg daily for depression to 60 mg daily for bulimia. 1

Major Depressive Disorder

Adults

• Start at 20 mg once daily in the morning 1
• This dose is sufficient for most patients to achieve satisfactory response 1
• If insufficient improvement after several weeks, increase dose 1
• Doses above 20 mg can be given once daily (morning) or twice daily (morning and noon) 1
• Maximum dose: 80 mg/day 1
• Full therapeutic effect may be delayed 4 weeks or longer 1

Pediatric Patients (Children and Adolescents)

• Start at 10-20 mg/day 1
• After 1 week at 10 mg, increase to 20 mg/day 1
• Lower weight children should start at 10 mg/day and may remain at this dose as target due to higher plasma levels 1
• Fluoxetine is the only FDA-approved SSRI for depression in children and adolescents 2

Maintenance Treatment

• Continue for 4-12 months after remission for first episode 3
• Longer duration for recurrent depression 3
• Efficacy maintained up to 38 weeks at 20 mg/day in adults 1
• Weekly dosing option (Prozac Weekly) available after stabilization on 20 mg daily, initiated 7 days after last daily dose 1

Obsessive-Compulsive Disorder

Adults

• Start at 20 mg/day in the morning 1
• Recommended dose range: 20-60 mg/day 2, 1
• Doses up to 80 mg/day have been well tolerated but maximum should not exceed 80 mg/day 1
• Allow 8-12 weeks to determine efficacy, though some improvement may be seen within 2 weeks 2
• Full therapeutic effect may be delayed up to 5 weeks or longer 1
• Doses above 20 mg can be given once daily or twice daily 1

Pediatric Patients

• Adolescents and higher weight children: Start at 10 mg/day, increase to 20 mg/day after 2 weeks 1
• Recommended range: 20-60 mg/day 1
• Lower weight children: Start at 10 mg/day 1
• Recommended range: 20-30 mg/day 1
• Experience with doses >20 mg is minimal in this population 1

Maintenance

• Continue for minimum 12-24 months after remission, though longer treatment often necessary due to relapse risk 2
• OCD is a chronic condition warranting long-term treatment 1
• Efficacy maintained up to 6 months in controlled trials 1

Bulimia Nervosa

Adults Only

• Recommended dose: 60 mg/day administered in the morning 1
• This is the only dose proven superior to placebo 1
• May titrate up to target dose over several days if needed 1
• Doses above 60 mg/day have not been systematically studied 1
• Efficacy maintained up to 52 weeks at 60 mg/day 1

Panic Disorder

Adults

• Start at 10 mg/day 1
• Increase to 20 mg/day after 1 week 1
• 20 mg/day was the most frequently administered dose in clinical trials 1
• Consider dose increase after several weeks if no improvement 1
• Doses above 60 mg/day have not been systematically evaluated 1

Special Populations and Dosing Considerations

Hepatic Impairment

• Use lower or less frequent dosing across all indications 1

Elderly Patients

• Consider lower or less frequent dosing 1
• Paroxetine may be less ideal than fluoxetine in elderly due to anticholinergic effects 3

Renal Impairment

• Dosage adjustments not routinely necessary 1

Patients on Multiple Medications

• Consider lower or less frequent dosing 1
• Fluoxetine inhibits CYP2D6, CYP2C, and CYP3A4, requiring vigilance for drug interactions 4

Pregnancy (Third Trimester)

• Carefully weigh risks versus benefits 1
• Consider tapering in third trimester due to neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding 1

Critical Monitoring and Safety Considerations

Initiation Phase

• Contact within first week (in-person or telephone) to assess adherence, adverse effects, and understanding of treatment 2
• Monitor closely for suicidality, especially in adolescents on fluoxetine 2
• FDA black-box warning requires close observation for clinical worsening, suicidality, and unusual behavior changes, particularly during initial months and dose changes 2

Adverse Effects

• Most common: nausea, nervousness, insomnia 5
• Significantly fewer anticholinergic effects than tricyclic antidepressants 5
• Sexual dysfunction can occur 4
• Risk of behavioral activation or switch to mania 2
• Starting at higher doses increases risk of deliberate self-harm and suicide-related events 2

Low-Dose Strategy for Panic Disorder

• Consider starting at 5 mg/day and gradually increasing to 20 mg over 1 week for patients with panic disorder who may be intolerant of standard dosing 6
• Approximately 28% of depressed patients cannot tolerate 20 mg, with half benefiting from lower doses 6

Discontinuation

• Taper gradually over 10-14 days to limit withdrawal symptoms 3
• Fluoxetine has longer half-life than other SSRIs, reducing but not eliminating discontinuation syndrome risk 3
• Allow at least 5 weeks after stopping fluoxetine before starting an MAOI due to long half-life 1
• At least 14 days must elapse between stopping an MAOI and starting fluoxetine 1

Treatment-Resistant OCD: Augmentation Strategies

Evidence-Based Approaches

• Augmentation with CBT has larger effect sizes than antipsychotic augmentation 2
• If CBT unavailable or not tolerated, consider pharmacological augmentation 2
• Fluoxetine plus clomipramine significantly superior to fluoxetine plus quetiapine in SSRI-resistant OCD 2
• Critical warning: Combining clomipramine with fluoxetine increases blood levels of both drugs, risking seizures, arrhythmias, and serotonin syndrome 2
• Antipsychotic augmentation (risperidone, aripiprazole) has evidence but modest effect size—only one-third achieve meaningful response 2
• Glutamatergic agents (N-acetylcysteine, memantine) show promise for treatment-resistant cases 2

Combination Serotonergic Agents

• Exercise extreme caution when combining two or more serotonergic drugs due to serotonin syndrome risk 7
• Serotonin syndrome can be fatal, presenting with mental status changes, neuromuscular hyperactivity, autonomic instability, fever, seizures, and arrhythmias 7
• Fluoxetine's very long half-life increases drug accumulation risk when combined with other serotonergic agents 7
• If combination absolutely necessary, start second agent at low dose with slow titration and close monitoring 7

Comparative Context

Versus Other Antidepressants

• Comparable efficacy to tricyclic antidepressants (imipramine, amitriptyline, doxepin) but with superior tolerability profile 5
• Similar efficacy to other SSRIs (sertraline, paroxetine) in available comparisons 8, 4
• Safer in overdose than tricyclics and MAOIs 5
• Does not affect cardiac conduction in patients without pre-existing cardiovascular disease 5

First-Line Status

• SSRIs including fluoxetine are first-line agents for OCD due to better tolerability than clomipramine, supporting long-term treatment 2
• Fluoxetine 60 mg daily is first-line for bulimia nervosa alongside CBT 2