Handan Gunduz-Bruce, M.D., Christopher Silber, M.D., Inder Kaul, M.D., Anthony J. Rothschild, M.D., Robert Riesenberg, M.D., Abdul J. Sankoh, Ph.D., Haihong Li, Ph.D., Robert Lasser, M.D., Charles F. Zorumski, M.D., David R. Rubinow, M.D., Steven M. Paul, M.D., Jeffrey Jonas, M.D., et al. Abstract BACKGROUND Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of […]
