Discussion
psychiatric, MDD, depression, Depression, suicidality
SECONDARY, DISORDERS
The demographics and baseline characteristics in this study, such as gender, age, and CDRS-R total score, were generally similar to those in a placebo-controlled double-blind study of duloxetine previously conducted in Japan for adolescent MDD (Saito et al., For the primary endpoint, time to relapse in the double-blind period, no statistically significant difference was observed between the two groups (This was numerically higher than the HR of 2.47 assumed when the study was planned, indicating a relapse-preventive effect of ESC. Compared with the log-rank test, the generalized Wilcoxon test, which is more sensitive to a difference between groups in the relapse at an early stage, was used as a In this study, although the HR for time to relapse was numerically higher than the 2.47 (assumed when the study was planned), no statistically significant differences were observed in the log-rank test conducted as primary analysis. The reason for this was considered to be a lack of power due to the fact that the number of relapsed patients was lower than expected. Based on the U.S. fluoxetine study (Emslie et al., There were only two relapse prevention studies for adolescent depression available as a reference for relapse rates at the time this study was planned: the U.S. fluoxetine study and the U.S. citalopram study (Cheung et al., This study was a 35-site multicenter trial, whereas the U.S. fluoxetine trial (Emslie et al., This study included psychoeducation provided once a month by a trained practitioner using materials developed for this study, and this may be another reason given the reported preventive effects of psychoeducation (Prieto-Vila et al., The results of the secondary endpoints in the open-label period were not greatly different from those in the U.S. adolescent MDD study (Esmile et al., 2009), and did not provide evidence against the efficacy of ESC.For all secondary endpoints in the double-blind period, the ESC group showed a trend toward improvement compared with the placebo group at week 48, and four of six endpoints, including change from start of the double-blind period in CDRS-R total score, were statistically significantly different between the two groups. In addition, change in CDRS-R total score, change in CGI-S and CGI-I showed greater differences in the two groups than in the U.S. adolescent MDD study (Esmile et al., 2009), although the study design and duration were different (Comparison of Scores with Escitalopram Adolescent Study in the United StatesMean difference between groups (ESC-placebo) of changes from baseline adjusted for start of double-blind period.Difference between groups (ESC-placebo) in ANCOVA modeling with treatment arm and medical organization as factors and baseline values as covariates.ANCOVA, analysis of covariance; CDRS-R, Children's Depression Rating Scale-Revised; CGI-I, Clinical Global Impression-Improvement Scale; CGI-S, Clinical Global Impression-Severity Scale; ESC, escitalopram; LOCF, Last Observation Carried Forward.These results in the double-blind and open-label period suggest that ESC may be effective in preventing relapse.In terms of safety profile, the AEs in this study were generally similar to those previously observed in adult clinical studies in Japan (Hirayasu, The risk of suicide associated with antidepressants used to treat MDD and other psychiatric disorders in pediatric patients is of particular concern. In 2004, the FDA issued a warning to include the risk of suicidality in the Package Insert for all antidepressants used to treat children, adolescents, and young adults (Fornaro et al., 