What is the starting dose, titration schedule, and maximum dose of fluoxetine (selective serotonin reuptake inhibitor, SSRI) for the treatment of Obsessive-Compulsive Disorder (OCD)?

Fluoxetine Dosing for OCD

For OCD treatment, start fluoxetine at 20 mg daily in the morning, increase to 40-60 mg daily after several weeks if needed, with a maximum dose of 80 mg daily. 1

Starting Dose

• Initiate treatment at 20 mg/day administered in the morning for most adult patients 1
• For lower weight children and adolescents, start at 10 mg/day, then increase to 20 mg/day after 2 weeks 1
• For higher weight children and adolescents, start at 10 mg/day for 2 weeks, then increase to 20 mg/day 1

Titration Schedule

• After several weeks at the initial dose, increase the dose if insufficient clinical improvement is observed 1
• The recommended therapeutic dose range is 20-60 mg/day for adults 1
• For adolescents and higher weight children, the dose range is 20-60 mg/day 1
• For lower weight children, the dose range is 20-30 mg/day 1
• Doses above 20 mg/day can be given once daily (morning) or twice daily (morning and noon) 1

Maximum Dose

• The maximum fluoxetine dose should not exceed 80 mg/day 1
• Doses up to 80 mg/day have been well tolerated in open studies of OCD 1
• Higher doses (40-80 mg daily) are typically necessary for OCD compared to depression treatment 2
• Meta-analyses confirm that higher SSRI dosing for OCD is associated with greater efficacy, though also higher dropout rates due to adverse effects 2

Time to Therapeutic Effect

• Do not evaluate efficacy before 8 weeks of treatment, as the full therapeutic effect may be delayed until 5 weeks or longer 1, 3
• Maximal improvement may not occur until week 12 or later 2
• Some early improvement may begin within 2-4 weeks, but full response requires 8-12 weeks at an adequate dose 4

Treatment Duration

• Continue maintenance treatment for a minimum of 12-24 months after achieving remission to prevent relapse 2, 5
• OCD is a chronic condition requiring prolonged treatment 1
• Efficacy has been maintained for up to 3 years in long-term studies 3

Critical Safety Considerations

• CYP2D6 poor metabolizers are at significantly higher risk for toxicity and QT prolongation at the high doses required for OCD (60-80 mg), with fluoxetine exposure being 3.9-fold higher at 20 mg and 11.5-fold higher at 60 mg in poor metabolizers versus extensive metabolizers 2
• The FDA has issued warnings about QT prolongation risk in CYP2D6 poor metabolizers, with documented fatal cases 2
• Consider pharmacogenetic testing or alternative SSRI before initiating high-dose therapy in patients with known CYP2D6 poor metabolizer status or family history of sudden cardiac death 2
• Fluoxetine is a potent CYP2D6 inhibitor that converts approximately 43% of extensive metabolizers to poor metabolizer phenotype during chronic use, creating significant drug-drug interaction risks 2

Common Pitfalls to Avoid

• Do not discontinue treatment prematurely before 8-12 weeks at an adequate dose, as therapeutic response emerges slowly 1, 3
• Do not use doses lower than 40-60 mg/day for most OCD patients, as higher doses are generally necessary compared to depression treatment 2, 3
• Do not ignore early adverse effects like nervousness or insomnia, as these may actually predict good response to fluoxetine 3
• Be aware that fluoxetine causes more drug-drug interactions than some other SSRIs due to potent CYP2D6 inhibition 2