Esketamine Monotherapy Shows Rapid Efficacy in Treatment-Resistant Depression

This phase 4 trial provides the first placebo-controlled evidence that intranasal esketamine works without a concomitant oral antidepressant, offering an option for treatment-resistant depression (TRD) patients intolerant to standard therapy.

esketamineintranasal esketamineSpravatoNMDA receptor antagonisttreatment-resistant depressionmajor depressive disordermonotherapyrandomized controlled trialpsychopharmacologyMADRS Psychiatry / Psychopharmacology

Background Information

Esketamine offers new hope for treatment-resistant depression monotherapy.

Esketamine nasal spray may offer a new monotherapy option for treatment-resistant depression (TRD) in patients intolerant to oral antidepressants. In this trial, esketamine significantly reduced Montgomery-Asberg Depression Rating Scale (MADRS) scores at day 28 with LS mean differences of -5.1 for 56 mg and -6.8 for 84 mg compared to placebo. This study suggests esketamine monotherapy is effective for TRD, but the high rate of reported adverse effects like nausea and dissociation should be considered. Esketamine nasal spray shows efficacy as a monotherapy for TRD, but monitor for adverse effects.

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Authors: Janik A, Qiu X, Lane R, Popova V, Drevets WC, Canuso CM, Macaluso M, Mattingly GW, Shelton RC, Zajecka JM, Fu DJ

Citation: Janik A, Qiu X, Lane R, et al. Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA psychiatry. 2025;82(9):877-887. doi:10.1001/jamapsychiatry.2025.1317

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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