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Esketamine monotherapy efficacious in treatment‐resistant depression

The Brown University Psychopharmacology Update November 1, 2025 DOI: 10.1002/pu.31369 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Adults with treatment-resistant depression
Intervention Intranasal esketamine
Dose 56 and 84 mg
Duration 4-week trial
Topics Depression Esketamine
Key findings Twice-weekly intranasal esketamine at 56 and 84 mg significantly improved depressive symptoms compared with placebo in adults with treatment-resistant depression.

Abstract

Twice‐weekly dosing of intranasal esketamine resulted in significant improvement in depressive symptoms compared with placebo in adults with treatment‐resistant depression, a 4‐week trial has found. Esketamine doses of 56 and 84 mg both outperformed ­placebo in the post‐marketing trial. Study results were published online July 2, 2025, in JAMA Psychiatry.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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