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 can have potentially serious negative effects, including excessive sedation and sudden lack of consciousness, the FDA required a REMS (Risk Evaluation and Mitigation Strategy) for healthcare facilities searching for to manage Zulresso. (More information on the REMS might be found at www.zulressorems.com.) In response to the REMS, patients should be under 24-hour supervision with monitoring by an on-site medical skilled and continuous pulse oximetry to detect excessive sedation.
Despite considerable excitement about brexanolone as a brand 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 higher estimate the frequency and severity of opposed events reported in adults treated with brexanolone.
A Global Safety Database was used for the gathering of individual case safety reports (ICSRs). The researchers analyzed postmarketing surveillance data from a complete of 499 patients treated with brexanolone between June 2019 and December 2021. Antagonistic event (AE) listing from spontaneous and solicited ICSRs were analyzed. The evaluation didn’t 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 within the FDA-approved brexanolone package insert.
Serious Antagonistic Events Were Unusual
Overall, 137 ICSRs (50 solicited and 87 voluntary) were filed, with a complete of 396 AEs reported. Of the 17 serious AEs reported, 12 were symptoms of psychiatric illness (e.g., suicidal ideation, anxiety). There have been 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 lack 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 didn’t 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.
On this postmarketing surveillance data evaluation, excessive sedation and lack of consciousness when receiving brexanolone occurred at lower rates (< 1% [3/499] and 0% [0/499] of patients, respectively) than previously reported in accomplished clinical trials. Also reassuring is the indisputable fact that no recent safety concerns were reported. That’s excellent news for patients inquisitive about this treatment; nevertheless, there just isn't yet adequate data to revise the REMS that's currently in place.
Ruta Nonacs, MD, PhD
References
Garafola S, Shiferaw E, Dev V. Safety of Brexanolone in Adults with Postpartum Depression: Postmarketing Surveillance Data. Drugs Real World Outcomes. 2023 Jun 6.