Zuranolone for the Treatment of Postpartum Depression.

Abstract

OBJECTIVE:

Postpartum depression (PPD) is a common perinatal 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 45-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in depressive 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.

• Authors: Kristina M Deligiannidis, Samantha Meltzer-Brody, Bassem Maximos, E Quinn Peeper, Marlene Freeman, Robert Lasser, Amy Bullock, Mona Kotecha, Sigui Li, Fiona Forrestal, Nilanjana Rana, Manny Garcia, Bridgette Leclair, James Doherty
• Journal: The American journal of psychiatry (Am J Psychiatry) Vol. 180 Issue 9 Pg. 668-675 (09 01 2023) ISSN: 1535-7228 [Electronic] United States
• PMID: 37491938 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• zuranolone
• Pregnanes
• Pyrazoles

Topics

• Pregnancy
• Humans
• Female
• Depression, Postpartum (drug therapy)
• Treatment Outcome
• Pregnanes (therapeutic use)
• Pyrazoles (therapeutic use)
• Double-Blind Method