Impact of demographic factors on the antidepressant effect: A patient-level data analysis from depression trials submitted to the Pharmaceuticals and Medical Devices Agency in Japan

A substantial and variable placebo response can cause unreliable findings in clinical trials designed to demonstrate the efficacy of antidepressants, and the high rate of failed trials represents a major obstacle in the development of new drugs for major depressive disorder (MDD). However, the influence of demographic and symptom factors on the antidepressant effect remains to be established. The purpose of this study was to estimate the magnitude of this influence. A patient-level meta-analysis of data from double-blind, randomized, placebo controlled trials involving the use of antidepressants for adults with MDD was performed. Data from five confirmatory trials evaluating the efficacy of four antidepressants that were submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) to support new drug applications were pooled (n = 1898). The change in the total score of 17-item Hamilton Depression Rating Scale (HDRS17) was the primary outcome of interest in our analysis. The changes in the total HDRS17 score in both the antidepressant medication group (ADM) and the placebo group (PBO) increased in relation to baseline symptom severity. Among older patients and those with a history of prior treatment with antidepressants, the changes in the total HDRS17 score decreased in ADM and remained static in PBO. There were no notable clinical symptoms that influenced the change in the total HDRS17 score. Baseline symptom severity, participant age and a history of previous treatment with antidepressants were suggested as moderators of the antidepressant effect. The drug-placebo difference in the estimated changes as a function of baseline symptom severity varied depending on the regression models used, and further studies are required to investigate appropriate models.