In 2019, brexanolone (marketed by Sage Therapeutics as Zulresso) was approved by the FDA for the treatment of postpartum depression (PPD). Because preliminary studies indicated that brexanolone may have potentially serious side effects, including excessive sedation and sudden loss of consciousness, the FDA required a REMS (Risk Evaluation and Mitigation Strategy) for healthcare facilities seeking to administer Zulresso. (More information on the REMS can be found at According to the REMS, patients must be under 24-hour supervision with monitoring by an on-site medical professional and continuous pulse oximetry to detect excessive sedation.

Despite considerable excitement about brexanolone as a new and rapidly effective treatment for postpartum depression, the restrictions dictated by the REMS significantly limited access to brexanolone. A recent study has examined postmarketing surveillance data to better estimate the frequency and severity of adverse events reported in adults treated with brexanolone.  

A Global Safety Database was used for the collection of individual case safety reports (ICSRs).  The researchers analyzed postmarketing surveillance data from a total of 499 patients treated with brexanolone between June 2019 and December 2021. Adverse event (AE) listing from spontaneous and solicited ICSRs were analyzed. The analysis did not include data from clinical trial safety reports. AEs were classified as serious or nonserious as defined by FDA seriousness criteria. AEs were classified as listed or unlisted, depending on whether or not they were included in the FDA-approved brexanolone package insert.

Serious Adverse Events Were Uncommon

Overall, 137 ICSRs (50 solicited and 87 voluntary) were filed, with a total of 396 AEs reported. Of the 17 serious AEs reported, 12 were symptoms of psychiatric illness (e.g., suicidal ideation, anxiety). There were two serious AE reports of excessive sedation. The remaining three serious AEs included seizure (n=1), hypoxia (n=1), and administration site conditions (n = 1). No reports of loss of consciousness were received.

In total, two serious and one nonserious reports of excessive sedation AEs were recorded; all cases resolved after stopping the brexanolone infusion and did not require any additional medical treatment. The three reported events of excessive sedation were similar in nature and severity to those previously reported in clinical trials.

In this postmarketing surveillance data analysis, excessive sedation and loss of consciousness when receiving brexanolone occurred at lower rates (< 1% [3/499] and 0% [0/499] of patients, respectively) than previously reported in completed clinical trials. Also reassuring is the fact that no new safety concerns were reported. That’s good news for patients interested in this treatment; however, there is not yet adequate data to revise the REMS that is currently in place.

Ruta Nonacs, MD, PhD


Garafola S, Shiferaw E, Dev V.  Safety of Brexanolone in Adults with Postpartum Depression: Postmarketing Surveillance Data.  Drugs Real World Outcomes. 2023 Jun 6.

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