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Rapid-Acting Antidepressant Therapies

Bashkim Kadriu, Subha Subramanian, Z. Deng, Ioline D. Henter, Lawrence T. Park, Carlos A. Zarate

October 23, 2018 preprint DOI: 10.31234/osf.io/xwk57 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review
Interventions Ketamine Esketamine Nitrous oxide Scopolamine GLYX-13 Buprenorphine Sleep deprivation
Key findings Novel glutamatergic agents such as ketamine and esketamine offer rapid antidepressant effects and high remission rates, and can rapidly reduce suicidal thoughts.

Abstract

Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant effects as well as high remission rates, making them attractive therapeutic options. This chapter reviews the evidence for the antidepressant efficacy of several novel therapeutics, including ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine, as well as interventional techniques such as sleep deprivation. Notably, ketamine and esketamine also rapidly reduce suicidal thoughts, making them attractive solutions in an emergency setting. Because studying the rapid onset of antidepressant effects associated with these agents has also improved our understanding of the neurocircuitry and neural signaling systems underlying MDD, some pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed.