Efficacy evaluation
depressive symptoms
ADVERSE EFFECTS, SECONDARY, REMISSION, RELAPSE
Efficacy was assessed for relapse and CDRS-R, CGI-S, and Clinical Global Impression-Improvement (CGI-I) Scale. Relapse was defined as (1) worsening of depressive symptoms observed for at least 2 weeks during the double-blind period, and total CDRS-R score of 40 or higher, or (2) investigators deem that treatment must be changed (regardless of the CDRS-R total score). To judge relapse objectively, evaluation was performed by three independent Central Assessment Committee members.The committee members reviewed the information on patients who discontinued treatment during the double-blind period and were considered likely to relapse based on the reason for discontinuation (e.g., lack of efficacy of the investigational drug or adverse effects), and neutrally judged relapse as to whether the patient met the definition. Patients judged to have relapsed by two or more committee members were deemed to have relapsed.CDRS-R, CGI-S, and CGI-I scores were determined by the investigators after training to ensure uniform ratings. The primary endpoint was time to relapse in the double-blind period. In the double-blind period, secondary endpoints were relapse, change from start of double-blind period in CDRS-R total score, change from start of double-blind period in CGI-S, CGI-S worsening, CGI-I, and CGI-I improvement.If the CGI-S increased by 2 or more from start of double-blind period, this was defined as worsening, and a CGI-I of 2 or less (“very much improved” or “much improved”) was defined as improvement. In the open-label period, secondary endpoints were change from baseline in CDRS-R total score, change from baseline in CGI-S, CGI-I, CGI-I improvement, remission, and response at week 12.