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Ketamine, Esketamine, and A New Generation of Antidepressants

Samuel T. Wilkinson, Brandon M. Kitay

Psychiatric Annals February 1, 2020 DOI: 10.3928/00485713-20200113-02 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Interventions Esketamine Brexanolone AXS-05 SAGE-217
Topics Esketamine Ketamine
Key findings The review reports that esketamine is approved for treatment-resistant depression and brexanolone for postpartum depression, both subject to FDA REMS requirements that pose challenges to clinical adoption; it also reviews late-stage compounds AXS-05 and SAGE-217.

Abstract

Since the discovery of its rapid-acting antidepressant properties, ketamine has helped stimulate a new line of research in the development of rapid-acting antidepressants based on the glutamate and gamma-aminobutyric acid neurotransmitter systems. An intranasal version of the S-enantiomer of ketamine (esketamine) recently received regulatory approval as a therapy for treatment-resistant depression (TRD). Here we review the clinical evidence of esketamine for TRD, challenges to its adoption in clinical practice, and the regulatory requirements imposed by the US Food and Drug Administration (FDA) through a risk evaluation and mitigation strategy (REMS). Brexanolone, an exogenous formulation of allopregnanolone, also recently received FDA approval for the treatment of postpartum depression and is likewise subject to a REMS. Other compounds in late-stage development, including AXS-05 and SAGE-217, are also reviewed. [ Psychiatr Ann . 2020;50(2):54–61.]