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February 2018

The Promise of Intranasal Esketamine as a Novel and Effective Antidepressant

Author Affiliations
  • 1NORMENT-KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
JAMA Psychiatry. 2018;75(2):123-124. doi:10.1001/jamapsychiatry.2017.3738

Nearly one-third of people with major depressive disorder are considered to have treatment-resistant depression (TRD).1 This diagnosis is a serious health concern due to its consequences for each affected individual and its associated economic burden on society owing to the prevalence of TRD.1,2 Despite the large public health influence, the principal mechanisms of action of pharmacologic agents used for the treatment of depression have remained largely unaltered since the introduction of selective serotonin-reuptake inhibitors in the 1980s. Moreover, current treatments are associated with delayed efficacy onset and inadequate remission rates. The N-methyl-d-aspartate receptor antagonist ketamine has emerged as a promising therapeutic agent, with intravenous administration demonstrating rapid antidepressant effects and striking response rates.3 In this issue of JAMA Psychiatry, Daly and colleagues4 present intriguing findings from the first clinical trial of intranasal esketamine hydrochloride (the more potent S-enantiomer of ketamine) adjunctive to oral antidepressants in TRD, reporting on its efficacy, safety, and dose response.

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