Insufficient Evidence for Neurosteroid Drugs in Managing Postnatal Depression

Recent research indicates that current evidence does not strongly support the use of new neurosteroid GABAA receptor positive allosteric modulators, such as Zuranolone, Brexanolone, and Ganaxolone, for treating postnatal depression. Antidepressants remain the primary pharmacological treatment, though they often provide limited relief for some women. These neurosteroid drugs were developed as promising alternatives, targeting the GABA system involved in brain activity regulation.

A comprehensive review published in the Cochrane Database of Systematic Reviews, led by scientists from King's College London, examined six U.S.-based randomized controlled trials involving 674 women. The studies investigated the efficacy of these neurosteroids—delivered intravenously or orally—in reducing postnatal depression symptoms.

The findings suggest that intravenous Brexanolone and Ganaxolone may have little to no significant benefit over placebo. Meanwhile, oral Zuranolone appeared to modestly reduce depressive symptoms over a 45-day period but was associated with increased adverse effects, such as drowsiness. Despite Zuranolone's potential, experts emphasize that it is premature to recommend its use in clinical practice due to the lack of comparative studies with established antidepressants and safety data for breastfeeding women.

Currently, these drugs are not approved outside the United States. Researchers advocate for further investigations that compare these neurosteroids with standard treatments, incorporate longer follow-up periods, and evaluate safety for breastfeeding mothers. Dr. Claire Wilson from King's IoPPN highlighted that, although Zuranolone shows promise, more comprehensive trials are essential to determine its effectiveness and safety profile.

The review underscores the need for additional research to validate these agents' efficacy and safety in diverse clinical settings before they can be integrated into routine postpartum depression treatment protocols.