Cochrane Database Syst Rev

Postnatal depression: Zuranolone likely improves symptoms but may increase maternal adverse events

July 17, 2025

Oral zuranolone probably improves depression response, severity, and remissions—yet it also probably increases maternal adverse events (e.g., somnolence) compared with placebo—according to moderate‐certainty evidence in this Cochrane review on neurosteroid GABA-A receptor-positive allosteric modulator drugs for postnatal depression. However, no studies were available comparing the drugs to active treatments (pharmacological, psychosocial, or psychological).

Study details. Researchers identified 6 industry-sponsored, US-based, placebo‐controlled RCTs (N = 674 women with depression in the first 12 months post-childbirth) comparing neurosteroid GABA-A receptor-positive allosteric modulators (brexanolone, ganaxolone, zuranolone). Hamilton Rating Scale for Depression (HAMD‐17) scores were used to assess response; Barkin Index of Maternal Functioning was reported in some studies.

Results: Oral zuranolone (N = 349 women studied) is probably linked to improvements in depression response (risk ratio [RR], 1.26; 95% confidence interval [CI], 1.03-1.55), depression severity (mean difference, ‐3.79; 95% CI, ‐5.60 to ‐1.97), as well as remissions (RR, 1.65; 95% CI, 1.22-2.22) at 45 days from treatment start, according to moderate‐certainty evidence. However, it probably also increases maternal adverse events rates (RR, 1.24; 95% CI, 1.03-1.48). Most frequent adverse event: somnolence. No study reported on quality of life; however, one study reported positive Barkin Index of Maternal Functioning results with zuranolone—but the evidence was deemed low-certainty. Results on the effectiveness of other receptor-positive allosteric modulator drugs, such as IV brexanolone (no longer available in the U.S.), was of low certainty.

Source:

Wilson CA, et al. (2025, June 26). Cochrane Database Syst Rev. Brexanolone, zuranolone and related neurosteroid GABA_A receptor positive allosteric modulators for postnatal depression. https://pubmed.ncbi.nlm.nih.gov/40562419/