Zuranolone in Postpartum Depression: A Review of the First Oral Neurosteroid Treatment

Abstract

Background: Postpartum depression (PPD) is a severe mood disorder affecting 1 in 7 postpartum women. It significantly impacts maternal functioning and infant development. SSRIs are currently the first-line treatment, but require 4-8 weeks to take effect and show variable efficacy. The neurosteroid hypothesis connects PPD symptoms to an abrupt drop in allopregnanolone after childbirth. Zuranolone, a synthetic modulator of the GABA-A receptor, is the first oral neurosteroid specifically indicated for postpartum depression.  

Aim: This review analyzes zuranolone’s pharmacology, Phase III clinical efficacy, and its practical use for postpartum depression.  

Material and methods: We conducted a comprehensive literature review using PubMed. Search terms included „zuranolone", „neurosteroid", and "postpartum depression”. We reviewed publications from 2015 to 2025, focusing on Phase III clinical studies, pharmacological analyses, and FDA/EMA regulatory documents.  

Results: Zuranolone is administered as 50 mg once daily for 14 days. Two Phase III randomized, placebo-controlled trials (n=150, n=196) evaluated zuranolone for moderate to severe postpartum depression. In the pivotal trial, the least-squares mean difference on the HAM-D was -4.0 versus placebo (95% CI: -6.3 to -1.7; p=0.001). Response rates were 57.0% versus 38.9% (p=0.021), and remission rates were 26.9% versus 16.7%. Effects were seen by day 3 and lasted through day 45. 

Conclusions: Zuranolone represents a significant therapeutic advance in the treatment of postpartum depression. It offers immediate symptom relief during the critical early postpartum period. Further research is needed to assess effectiveness and safety in a more heterogeneous population, as well as the long-term effects in mood disorders.