Evaluating brexanolone for the treatment of postpartum depression

ABSTRACT

Introduction: Postpartum depression (PPD) is a serious and common complication of childbirth that can have deleterious effects not only on the mother but on the cognitive and behavioral development of exposed children. Brexanolone is a novel, soluble synthetic formulation of the natural hormone allopregnanolone and acts as a positive allosteric modulator of the gamma-aminobutyric acid A receptor (GABAA). Allopregnanolone levels dramatically decrease during the postpartum time-period and some studies indicate lower serum levels of allopregnanolone during pregnancy in women that go on to develop PPD.

Areas covered: The author provides an overview of brexanolone as a treatment option for PPD including coverage of its pharmacokinetics, efficacy, safety, and tolerability. Furthermore, the author gives her expert perspectives on its use and its standing in the treatment armamentarium moving forward.

Expert opinion: Brexanolone represents a breakthrough for psychiatry due to its novel mechanism of action, its rapid onset of action, and its sustained effects without continued administration. It is appropriate for use in women with moderate to severe PPD. Experience with the medication and further research is needed to clarify whether the current recommended dosing regimen is required for efficacy.

KEYWORDS:

• Brexanolone
• allopregnanolone
• postpartum depression
• major depression
• GABA; neurosteroids

Article highlights

• Postpartum depression is a serious complication of pregnancy with significant morbidity and mortality.

• Brexanolone is the first pharmacologic agent specifically approved for the treatment of postpartum depression.

• Brexanolone can be thought of as a synthetic version of the neurosteroid allopregnanolone which acts as a positive allosteric modulator of the gamma-aminobutryic acid A receptor thus regulating the major inhibitory neurotransmitter in the brain.

• Brexanolone is given as a 3 day intravenous infusion and requires continuous pulse oximetry monitoring.

• Brexanolone reduces postpartum depression symptoms within hours of administration, results in remission in a large portion of patients and has sustained effects for at least 30 days after infusion.

• Brexanolone with its novel mechanism of action and its rapid, signifiicant and sustained response is an exciting breakthrough agent for psychiatry.

Declaration of interest

JL Payne has, over the past five years, received research funding from Sage Therapeutics. She has also served as a consultant for Sage Therapeutics and Janssen Pharmaceuticals and has a patent entitled ‘Epigenetic Biomarkers of Postpartum Depression’. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Additional information

Funding

This manuscript was supported by the author’s work at John Hopkins School of Medicine.