Objective: The aim of this study was to compare fluoxetine dosage titration to 40–60 mg/day with fixed fluoxetine 20-mg/day treatment for an additional 10 weeks in pediatric outpatients with major depressive disorder (MDD) who had not met protocol-defined response criteria after 9-week acute fluoxetine treatment.
Methods: Patients unresponsive (less than or equal to 30% decrease in Children's Depression Rating Scale—Revised [CDRS-R] score) after 9-week fluoxetine treatment were randomly reassigned to continue at 20 mg/day or to increase to 40 mg/day. After 4 weeks, patients unresponsive to 40 mg/day could receive 60 mg/day.
Results: Twenty-nine (29) patients, 9–17 years of age, received fluoxetine 40–60 mg/day (n = 14) or 20 mg/day (n = 15). At the conclusion of this study phase, 10 patients (71%) on 40–60 mg/day met the response criteria, versus 5 patients (36%) on 20 mg/day (p = 0.128). Mean CDRS-R scores improved in both treatment groups (fluoxetine 40–60 mg/day, –9.4; fluoxetine 20 mg/day, –1.5; p = 0.099). Adverse events were similar in both groups. However, this study phase was statistically underpowered for detecting differences between treatment groups.
Conclusion: More than two thirds of patients whose dosage was increased responded within 10 weeks, suggesting dose escalation may benefit some patients. Approximately one third of patients unresponsive to initial treatment with fluoxetine 20 mg responded to this fixed dosage within another 10 weeks. Fluoxetine 20–60 mg/day was well tolerated.
