Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used?

Abstract

Postpartum depression is considered to be a subtype of major depressive disorder that occurs in approximately 10–20% of mothers worldwide. However, in actuality, these numbers are likely underreported due to minimization and the stigma of mental illness. Until recently, there were no approved medications for the treatment of postpartum depression. Allopregnanolone is a naturally occurring neuroactive steroid whose serum levels decline precipitously following childbirth. This hormonal fluctuation has been postulated as playing a role in the pathophysiology of postpartum depression. Brexanolone is the first medication approved by the US Food and Drug Administration for the treatment of postpartum depression. Brexanolone is an intravenous proprietary formulation of allopregnanolone that can be administered to produce stable serum levels comparable with third-trimester concentrations in postpartum mothers. It is hypothesized to modulate neuronal excitability by functioning as an allosteric modulator of γ-aminobutyric acid-A receptors and is administered under monitoring as a 60 h continuous infusion. In this review, we will highlight the results of the clinical trial program, including efficacy and tolerability data. Practical and logistical considerations of brexanolone will be reviewed, as will its potential place in therapy for the treatment of postpartum depression.

GABA System Modifications During Periods of Hormonal Flux Across the Female Lifespan

“…It has been proposed that aberrant GABAergic activity and a failure to properly maintain E/I balance during the transition into the postpartum period may be a precipitating factor leading to postpartum depression (PPD), a disorder in new mothers characterized by symptoms such as sadness, cognitive impairment, and strained mother-infant interactions ( Deligiannidis et al, 2013 , 2016 ; Stewart and Vigod, 2019 ; Deems and Leuner, 2021 ). In particular, PPD is thought to arise, at least in part, when there is a failure of GABA A Rs to adapt to the abrupt decline in ALLO after birth ( Faden and Citrome, 2020 ; Meltzer-Brody and Kanes, 2020 ).…”

“…Recent advances have been made in the treatment of PPD through FDA approval for use of the GABA-modulating drug Brexanolone, a synthetic version of ALLO which stabilizes fluctuations in ALLO levels allowing GABA A Rs to steadily adjust. Brexanolone, a PAM of GABA A Rs, tempers the dramatic changes in E/I balance that arise postpartum due to ALLO withdrawal and, as a result, has been shown to improve mood, cognition, and mother-infant bonding in women with PPD ( Kanes et al, 2017 ; Dacarett-Galeano and Diao, 2019 ; Faden and Citrome, 2020 ; Meltzer-Brody and Kanes, 2020 ). The success of Brexanolone in treating PPD adds further credence to GABAergic dysfunction and withdrawal from ALLO as contributing factors involved in the pathophysiology of PPD.…”

Risk factors for postpartum depression in women undergoing elective cesarean section: A prospective cohort study

“…Several antidepressants seem to be safe during pregnancy and postpartum, but they should be weighed against the risk/benefit by clinicians ( 44 ). Brexanolone was firstly approved by the US Food and Drug Administration for the treatment of patients with PPD in recent years ( 45 ). In the future, many studies comparing brexanolone and conventional antidepressants are still needed.…”

Postpartum depression: A role for psychedelics?

“…Adverse effects include excessive sedation and sudden loss of consciousness during drug administration, requiring admission to a medical ward for brexanolone treatment (Meltzer-Brody et al, 2018). The cost of administering brexanolone is reported to be US$34,000, not including hospital admission costs (Faden and Citrome, 2020). The high cost and prolonged period of admission required for brexanolone treatment are barriers to its accessibility and generalisability.…”