Zuranolone for the Treatment of Postpartum Depression

Objective: Postpartum depression (PPD) is a common peri-natal complication with adverse maternal and infant outcomes. This study investigated the efficacy and safety of zuranolone, a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid, as an oral, once-daily, 14-day treatment course for patients with severe PPD.Methods: In this double-blind phase 3 trial, women with severe PPD were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15; key secondary endpoints were change from baseline in HAM-D score at days 3, 28, and 45 and change from baseline in Clinical Global Impressions severity (CGI-S) score at day 15. Adverse events were monitored.Results: Among 196 patients randomized (zuranolone, N=98; placebo, N =98), 170 (86.7%) completed the 4 5-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in de-pressive symptoms at day 15 (least squares mean [LSM] change from baseline in HAM-D score,-15.6 vs.-11.6; LSM difference,-4.0, 95% CI=-6.3,-1.7); significant improvement in depressive symptoms was also reported at days 3, 28, and 45. CGI-S score at day 15 significantly improved with zuranolone compared with placebo. The most common adverse events ($10%) with zuranolone were somnolence, dizziness, and sedation. No loss of consciousness, withdrawal symptoms, or increased suicidal ideation or behavior were observed. Conclusions: In this trial, zuranolone demonstrated significant improvements in depressive symptoms and was generally well tolerated, supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.