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Serial ketamine infusions not effective as adjunctive care for depression

The Brown University Psychopharmacology Update January 24, 2026 DOI: 10.1002/pu.31401 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Patients receiving inpatient treatment for depression
Interventions Ketamine Midazolam
Topics Ketamine Depression Esketamine
Keywords Depression economics Placebo Midazolam Randomized controlled trial Cognition Anesthesia Clinical trial Adjunctive treatment Depressive symptoms
Key findings Up to eight infusions of ketamine were not more effective than a psychoactive placebo (midazolam) in reducing depressive symptoms or improving cognition and quality of life in patients receiving inpatient treatment for depression.

Abstract

Up to eight infusions of ketamine were not more effective than a psychoactive placebo in reducing depressive symptoms in patients receiving inpatient treatment for depression, a randomized trial has found. Patients receiving ketamine also showed no improvement relative to those receiving midazolam on measures of cognition and quality of life. Study results were published online Oct. 22, 2025 in JAMA Psychiatry .

Comparable studies

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

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
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

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