In a phase 3 trial of an investigational oral positive allosteric modulator of the γ-aminobutyric acid type A (GABAA) receptor, zuranolone 50 mg/day significantly improved depressive symptoms by day 15 and had a rapid time to effect of 3 days. “Zuranolone was generally well tolerated, with no new safety findings compared with previously studied lower dosages,” the authors report. “These findings support the potential of zuranolone in treating adults with major depressive disorder.”
In the randomized, double-blind, placebo-controlled trial, adult participants through age 64 with severe major depressive disorder self-administered zuranolone 50 mg or placebo once daily for 14 days. With a primary endpoint of change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15, the investigators found the following: “Of 543 randomized patients, 534 (266 in the zuranolone group, 268 in the placebo group) constituted the full analysis set. Compared with patients in the placebo group, patients in the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, −14.1 vs. −12.3). Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study (through day 42, with the difference remaining nominally significant through day 12). Two patients in each group experienced a serious adverse event; nine patients in the zuranolone group and four in the placebo group discontinued treatment due to adverse events.”