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Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development

Abstract

Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cognitive, behavioral, and emotional development with lasting consequences. There are a number of therapeutic interventions for postpartum depression including pharmacotherapy, psychotherapy, neuromodulation, and hormonal therapy among others, most of which have been adapted from the treatment of major depressive disorder outside of the peripartum period. Current evidence of antidepressant treatment for postpartum depression is limited by the small number of randomized clinical trials, underpowered samples, and the lack of long-term follow-up. The peripartum period is characterized by rapid and significant physiological change in plasma levels of endocrine hormones, peptides, and neuroactive steroids. Evidence supporting the role of neuroactive steroids and γ-aminobutyric acid (GABA) in the pathophysiology of postpartum depression led to the investigation of synthetic neuroactive steroids and their analogs as potential treatment for postpartum depression. Brexanolone, a soluble proprietary intravenous preparation of synthetic allopregnanolone, has been developed. A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration (decision due in March 2019). SAGE-217, an allopregnanolone analog, with oral bioavailability, was recently tested in a randomized, double-blind, placebo-controlled phase III study in severe postpartum depression, with reportedly positive results. Finally, a 3β-methylated synthetic analog of allopregnanolone, ganaxolone, is being tested in both intravenous and oral forms, in randomized, double-blind, placebo-controlled phase II studies in severe postpartum depression.

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Acknowledgments

We acknowledge Janice Lester, MLS, the Reference and Education Librarian at the Health Science Library of Long Island Jewish Medical Center at Northwell Health for her assistance with the literature review searches.

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Correspondence to Kristina M. Deligiannidis.

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This article was supported by a National Institutes of Health Grant (No. 5K23MH097794). Kristina M. Deligiannidis currently receives royalties from an National Institutes of Health Employee Invention.

Conflict of Interest

Kristina M. Deligiannidis has received research grant support as a site for the clinical trials of brexanolone and SAGE-217 and serves as a consultant for Sage Therapeutics. Ariela Frieder, Madeleine Fersh, and Rachel Hainline have no conflicts of interest that are directly relevant to the contents of this article. The views expressed in this article are those of the authors and do not necessarily reflect the position of the National Institutes of Health.

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Frieder, A., Fersh, M., Hainline, R. et al. Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. CNS Drugs 33, 265–282 (2019). https://doi.org/10.1007/s40263-019-00605-7

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