Around 10–20% of mothers worldwide have postpartum depression (PPD), which is regarded as a subtype of major depressive disorder. Due to minimization and the stigma associated with mental illness, these figures may be underreported.1 For the treatment of postpartum depression, there were no approved drugs up until recently. The first drug recognized by the US Food and Drug Administration for the treatment of postpartum depression is brexanolone.2
What is brexanolone and how does it work?
The serum levels of allopregnanolone, a naturally occurring neuroactive steroid, sharply decrease after childbirth. The pathogenesis of postpartum depression has been hypothesized to involve this hormone imbalance.3 Brexanolone is an allopregnanolone intravenous proprietary formulation that can be delivered to postpartum mothers to produce stable serum levels that are comparable to third-trimester amounts. It is given as a 60-hour continuous infusion while being monitored and is expected to affect neuronal excitability by acting as an allosteric modulator of -aminobutyric acid-A receptors.2
Brexanolone Has a Strong Antidepressant Effect
A metanalysis investigated brexanolone infusion's efficiency, acceptability, and safety in treating PPD.4 Included were two studies describing three randomized controlled trials (RCTs) with four active arms (n = 267) encompassing 156 PPD patients receiving brexanolone infusion and 111 PPD patients receiving a placebo. Women with PPD who got brexanolone had a considerably better reaction than those who received a placebo. This response began at 24 hours, peaked at 36 hours, and lasted until Day 7. Similar to how PPD women treated with brexanolone experienced a markedly better remission that began at 24 hours, peaked at 60 hours, and lasted for 72 hours.4 They concluded that for PPD, a single brexanolone infusion appears to produce an ultra-rapid, up to one-week-long antidepressant effect.4
Another meta-analytical study comprised adults with PPD who were randomly assigned to receive a 60-h infusion of brexanolone 90 g/kg/h (BRX90) or a placebo from the 3 trials. The 17-item Hamilton Rating Scale for Depression (HAMD-17) overall score, the HAMD-17 Anxiety/Somatization and Insomnia subscales, and the Clinical Global Impression of Improvement (CGI-I) scale were all given a change from baseline (CFB) score. Patients receiving BRX90 (n = 102) experienced a faster HAMD-17 reaction than those getting a placebo (n = 107).5 When compared to a placebo, brexanolone was related with a quick reduction in depression, anxiety, and sleeplessness symptoms in PPD women. These findings support the continued use of brexanolone in the management of PPD in adults.5
Challenges Facing Brexanolone Pharmacological Intervention for PPD
Only an intravenously administered version of brexanolone is available, which restricts its usefulness as a simple to administer PPD treatment. But zuranolone, an oral medication in development, is similar to brexanolone in terms of its molecular pharmacologic profile.5 Brexanolone is predicted to be reserved for patients with severe PPD because of its high cost, and in many cases, logistical and practical obstacles may exist that hinder the start of brexanolone treatment.5 Brexanolone must be delivered under close supervision in a medical facility for the duration of the 60-hour infusion due to the possibility of side effects. Brexanolone is unlike any other drug now on the market for the treatment of depression or PPD. Because of this, doctors have little experience using it, which may discourage them from recommending it.5
What is the final verdict for brexanolone?
Brexanolone is facing several obstacles, including continuous infusion, the need for an inpatient facility, the requirement for continuous pulse oximetry monitoring, and side effects like sedation that force patients to stop receiving the medication. Nonetheless, it is being lauded as a "breakthrough" drug. As was noted in the RCTs' positive findings regarding the clinical use of the medicine, they provided strong support for the safety, tolerability, and effectiveness of brexanolone. As a result, the FDA designated brexanolone as a "breakthrough medicine" and gave it a "priority review," which finally resulted in its approval. Brexanolone offers the promise of being successful in treating PPD and reducing the negative impact of this public health burden.
1. Howard LM, Molyneaux E, Dennis CL, et al. Non-psychotic mental disorders in the perinatal period. Lancet. 2014;384(9956):1775–1788. doi:10.1016/S0140-6736(14)61276-9.
2. Sage therapeutics announces FDA approval of ZULRESSO™ (brexanolone) injection, the first and only treatment specifically indicated for postpartum depression press release. News release. Sage Therapeutics; March 19, 2019. Accessed June 9, 2020. https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-announces-fda-approval-zulressotm-brexanolone
3. Kanes S, Colquhoun H, Gunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390(10093):480-489. doi:10.1016/S0140-6736(17)31264-3
4. Zheng W, Cai DB, Zheng W, Sim K, et al. Brexanolone for postpartum depression: A meta-analysis of randomized controlled studies. Psychiatry Research. 2019;279:83-89. doi:10.1016/j.psychres.2019.07.006
5. Epperson CN, Rubinow DR, Meltzer-Brody S et al. Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord. 2023;320:353-359. doi:10.1016/j.jad.2022.09.143
6. Faden J, Citrome L. Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used?. Ther Adv Psychopharmacol. 2020;10:2045125320968658. doi:10.1177/2045125320968658