Neuroactive steroid pill reduces postpartum depression symptoms in 2 weeks

A neuroactive steroid in pill form significantly reduced depressive symptoms and was generally well-tolerated among women with postpartum depression, according to results of a randomized clinical trial published in JAMA Psychiatry.

“Brexanolone was the first FDA-approved antidepressant for postpartum depression (and first-in-class antidepressant) and is rapid-acting; however, given that this medication is a 60-hour infusion given in a hospital-like setting, some women may not be able to access that rapid-acting medication,” Kristina M. Deligiannidis, MD, director of women’s behavioral health at Zucker Hillside Hospital and associate professor at the Feinstein Institutes for Medical Research in New York, told Healio Psychiatry. “Zuranolone, the investigational medication we examined in this clinical trial, is a related neuroactive steroid with a similar mechanism of action as brexanolone (given intravenously), but zuranolone is given for 14 days once daily in the evening at home.”

Delgiannidis and colleagues aimed to assess the efficacy and safety of zuranolone (SAGE-217; Sage Therapeutics Inc.) in postpartum depression (PPD). In the current phase 3, double-blind, randomized, outpatient, placebo-controlled clinical trial conducted between January 2017 and December 2018 across 27 U.S. sites, they included women aged 18 to 45 years (mean age, 28.3 years). Other eligibility criteria were being 6 months or fewer postpartum, having PPD with a major depressive episode having begun in the third trimester or 4 weeks after delivery and having a baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) score of 26 or higher. The researchers randomly assigned 76 patients to placebo and 77 to zuranolone 30 mg, administered orally each evening for 2 weeks. Change from baseline in HAMD-17 score for zuranolone compared with placebo at day 15 served as the primary endpoint. Changes from baseline in HAMD-17 total score at other time points, HAMD-17 response and remission rates, Montgomery-Åsberg Depression Rating Scale score and Hamilton Rating Scale for Anxiety score served as secondary endpoint. The researchers assessed safety according to adverse events and clinical assessments.

Results showed significant improvements in day 15 HAMD-17 score from baseline for zuranolone compared with placebo, for a 17.8 vs. 13.6 difference, respectively. From day 3 through day 45, the researchers observed sustained differences in HAMD-17 scores that favored zuranolone. Further, they noted sustained differences at day 15 that favored zuranolone in HAMD-17 response (OR = 2.63; 95% CI, 1.34-5.16), HAMD-17 score remission (OR = 2.53; 95% CI, 1.24-5.17), change from baseline for Montgomery-Åsberg Depression Rating Scale score (difference = 4.6; 95% CI, 8.3 to 0.8) and Hamilton Rating Scale for Anxiety score (difference = 3.9; 95% CI, 6.7 to 1.1). One patient in the zuranolone group experienced confusional state and one in the placebo group experienced pancreatitis, both of which were considered a serious adverse event. In the zuranolone group, one patient discontinued because of an adverse event compared with none in the placebo group.

“As PPD can have devastating effects on both mother and infant (and family), reducing suffering from PPD as rapidly as possible to restore maternal emotional health is of the utmost importance and is the drive for developing new therapeutics for it,” Deligiannidis said.