Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review

Amber N Edinoff,Omar Viswanath,P Scott Barrilleaux,Ivan Urits,David Lewis,Alan D Kaye,Grace Hunt,Adam Kaye,Amira S Odisho,Kendall Lewis,Amir Kaskas,John Morgan,Elyse M Cornett

doi:10.3389/fpsyt.2021.699740

Abstract

Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABAA receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABAA and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression.

Highlights

Postpartum depression (PPD) can result in mothers’ adverse health consequences, disrupt the mother-child relationship, and causes distress to the family unit [1, 2].PPD is a mood disorder that is defined as a major depressive disorder with postpartum onset
Four women with a Hamilton Rating Scale for Depression (HAM-D) score >20 were admitted 14–20 days following the birth of their child
This study reported a mean initial HAM-D score of 26.5 ± 4.1 at time point 0 before treatment with brexanolone

Summary

INTRODUCTION

Postpartum depression (PPD) can result in mothers’ adverse health consequences, disrupt the mother-child relationship, and causes distress to the family unit [1, 2]. Additional studies have shown that decreased levels of allopregnanolone are associated with increased depressive symptoms in pregnant women [28], and increased allopregnanolone levels have been correlated with a decreased risk of developing PPD [29] As of this writing, there has been no randomized controlled trials looking at progesterone to treat postpartum depression. The study was a phase 2 trial 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. The researchers expanded upon these results, showing remission from postpartum depression was observed in 7 of the women receiving brexanolone treatment and that this effect was maintained until the end of the 30-day follow-up period; comparatively, remission was achieved in only 2 of the placebo-treated patients at 30-day follow-up following their treatment [30]. Each treatment was administered for 60 h, and the patients were followed for a 30-day period. 138 total

Results and findings

Conclusions

CONCLUSION