Volume 30, Issue 172, June 2026

Zuranolone as the First Oral Neuroactive Steroid for Postpartum Depression: Pharmacology, Clinical Efficacy, and Lactation Safety

Mateusz Kwiatkowski^1♦, Zofia Leżańska¹, Emil Pałyga¹, Joanna Sowińska¹, Aleksandra Cieślak¹, Sara Demkow¹, Natalia Paluszkiewicz¹, Katarzyna Marcinkowska¹, Karolina Siemińska¹, Sandra Bryg²

¹Faculty of Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland
²Faculty of Medicine, Medical University of Silesia in Katowice, Józefa Poniatowskiego 15, 40-055 Katowice, Poland

^♦Corresponding author
Mateusz Kwiatkowski, Faculty of Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland

ABSTRACT

Introduction: Postpartum depression is one of the most common mental illnesses associated with childbirth that occurs in about one out of every six mothers and has an impact on their offspring and relatives. For decades, pharmacologic treatment options were scant: SSRIs took weeks to work, and brexanolone, the only drug for PPD approved by the FDA, worked quickly but had a 60-hour inpatient infusion protocol that very few women got access to. FDA-approved in August 2023 as the first pill to treat postpartum depression, the drug acts as a positive allosteric modulator for GABA-A receptors and does everything that brexanolone was able to do, but is available to patients. Methods: A comprehensive search of PubMed and Google Scholar was done to find articles regarding randomized controlled trials, pharmacokinetics, safety studies, and lactation pharmacology related to zuranolone at phase 3. Results: Improvement in the 17-item Hamilton Depression Rating Scale (HAM-D-17) score is observed from days 3 to 15 for both phase 3 RCTs, while effects lasted up to day 45. Similar conclusions are drawn in a meta-analysis, and fewer antidepressants are used as concomitant medication. No serious adverse events occurred, and patients remained conscious and did not show increased suicidality from baseline. In light of the RIDs obtained in lactation data, it can be assumed that breastfeeding can be maintained during therapy. Conclusions: Zuranolone is a novel agent for the treatment of PPD, acting via a target-specific mechanism, with rapid onset and an oral route of administration.

Keywords: postpartum depression; zuranolone; neuroactive steroids; GABA-A receptor; allopregnanolone

Medical Science, 2026, 30, e100ms3903

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Published: 12 June 2026