Abstract
Objective: To evaluate the efficacy and safety of escitalopram (ESC) in a 48-week relapse prevention study in Japanese adolescents with major depressive disorder (MDD). Methods: This was a 48-week multicenter randomized double-blind placebo-controlled parallel-group study of patients aged 12-17 years with MDD. Patients received ESC for 12 weeks as an open-label treatment period (open-label period). Patients who achieved criteria for remission or response in the open-label period received either ESC or placebo for 36 weeks as a double-blind treatment period (double-blind period). The primary endpoint was the time to relapse during the double-blind period. Safety was evaluated in terms of type, incidence, and severity of adverse events. Results: Of the 128 patients who entered the open-label period, 80 patients entered the double-blind period, all of whom were in the primary analysis population. The primary endpoint, time to relapse, was marginally less than statistically significant between the ESC and placebo groups (p = 0.051, log-rank test). In the Cox proportional hazards model, the estimated hazard ratio [two-sided 95% confidence interval] for relapse in the placebo group versus the ESC group was 2.96 [0.94, 9.30]. There were statistically significant differences between the ESC and placebo groups in several secondary endpoints (change in Children's Depression Rating Scale-Revised, change in Clinical Global Impressions-Severity Scale, etc.). No notable safety/tolerability issues were observed in this study compared with the results of studies in Japanese adults with MDD. Conclusions: Superiority of ESC over placebo for relapse prevention in Japanese adolescents aged 12-17 years with MDD could not be verified with time to relapse evaluated by log-rank test. However, secondary endpoint results and a post hoc analysis of time to relapse suggest that ESC may be effective in preventing MDD relapse. No notable safety/tolerability issues were observed compared with the results of studies in Japanese adults with MDD. Study Registry Number: jRCT2080224520.