Table 1.

Safety and efficacy of brexanolone in treating postpartum depression in adults.

References	Groups studied and intervention	Results and findings	Conclusions
Kanes et al. (30)	Phase 2 study of brexanolone for the treatment of severe postpartum depression (HAM-D score >26) involving 21 women in a double-blind, randomized, placebo-controlled trial across four U.S. hospitals. Patients were randomized to receive either placebo (n = 11) or brexanolone (n = 10) intravenously, continuously for 60 h, after which patients were followed for 30 days	Results were quantified in terms of the Hamilton Rating Scale for Depression (HAM-D). At the 60-h mark, patients who received brexanolone had a deviation of 21.0 points from original HAM-D score (standard error 2.9) vs. the placebo score change of 8.8 points (standard error 2.8). Remission from postpartum depression (HAM-D score <7) was observed in 7 of the 10 brexanolone treatment, and this effect was maintained until the end of the 30-day follow-up period; this was the case with two of eleven placebo-treated patients at 30-day follow-up.4 out of 10 brexanolone patients experienced side effects as compared to 8 out of 11 in the placebo group. While no death or serious adverse events occurred, side effects most reported included: dizziness (n = 2 for brexanolone group and n = 3 for placebo), somnolence (n = 2 for brexanolone and n = 0 for placebo groups), sedation (N = 1 in brexanolone group vs. n = 0 in placebo) and a moderate adverse event did occur in the brexanolone group (sinus tachycardia).	Brexanolone results in clinically significant reduction in postpartum depression, and is well-tolerated by postpartum women.
Meltzer-Brody et al. (36)	Two double-blind, randomized, placebo-controlled trials were performed with brexanolone and discussed in this literature. In study 1, women 18–45 year of age with a Hamilton Rating Scale for Depression (HAM-D) score of >26 were randomly assigned 1:1:1 to receive intravenous brexanolone 90 μg/kg/h, intravenous brexanolone 60 μg/kg/h, or placebo. Each treatment was administered for 60 h, and the patients were followed for a 30-day period.	In study 1, 138 total participants were enrolled, n = 45 in the 90 microgram/kilogram/h group, n = 47 in the 60 μg/kg/h group, and n = 46 in the placebo group. Mean change from baseline (HAM-D) score at the 60-h mark was: decreased 19.5 (standard error 1.2) in the 60 μg group, decreased by 17.7 (standard error 1.2) with the 90 μg group, and 14.6 (standard error 0.8) in placebo group. Nineteen of the participants receiving 60 μg brexanolone, 22 of the 90 μg brexanolone group, and 22 of the placebo group experienced adverse events in study 1.	Brexanolone injection has potential as a novel therapeutic option for postpartum depression, resulting in clinically significant reductions in HAM-D score.
Kanes et al. (30)	Open-label proof-of-concept study involving women 18-45 years of age were enrolled in the study. Four women with a Hamilton Rating Scale for Depression (HAM-D) score >20 were admitted 14–20 days following the birth of their child. These participants received a level of brexanolone up-titrated for 12 h to a third trimester allopregnanolone level, and maintained at that level for 36 h, which was followed by a 12 h down-taper. Patients were monitored for one and a half days post infusion, and had follow-up on days 11 and 34.	Mean initial HAM-D score was 26.5 ± 4.1 at the beginning of the trial. At hour 60, HAM-D mean total score was 1.8 ± 1.5. At hour 84, the HAM-D mean score was 5.3 ± 2.9. From 24 h onward, all patients (n = 4) had total HAM-D scores of ≤7, indicating a remission from postpartum depression symptoms. Dose adjustments were required due to incidence in most participants (n = 3), but no serious adverse event occurred throughout this trial.	Allopregnanolone is supported as a player in the pathophysiology of postpartum depression, and brexanolone may play a therapeutic effect in the treatment of this condition.
Cooper et al. (45)	Analysis of 26 studies resulted in 6 studies comparing brexanolone and SSRI's in regard to the Hamilton Rating Scale for Depression (HAM-D) score. Matching-adjusted indirect comparisons were performed for brexanolone vs. placebo, SSRI vs. placebo, and brexanolone vs. SSRI, and data were reported in terms of change from baseline	Change from baseline was greater in women with postpartum depression being treated with brexanolone as compared with women being treated with SSRI's. change from baseline between brexanolone and SSRIs were 12.79 (8.04–17.53) [day 3], 5.87 (−1.62 to 13.37) [week 4] and 0.97 (−6.35 to 8.30) [last observation] for the HAM-D in both patient and clinician-reported outcomes	Brexanolone provides clinically similar or improved outcomes in treating women with postpartum depression