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Serial Ketamine Infusions as Adjunctive Therapy to Inpatient Care for Depression

A. Jelovac, Cathal Mccaffrey, Masashi Terao, E. Shanahan, Emma Whooley, Kelly Mcdonagh, Sarah Mcdonogh, Orlaith Loughran, Ellie Shackleton, Anna Igoe, Sarah Thompson, Enas Mohamed, D. Nguyen, Ciaran O’neill, Cathal Walsh, Declan M. Mcloughlin

JAMA Psychiatry October 22, 2025 DOI: 10.1001/jamapsychiatry.2025.3019 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized clinical trial Peer reviewed
Population Inpatients with moderate to severe depression
Intervention Intravenous ketamine
Topics Depression Esketamine Ketamine
Citations 13
Key findings Repeated intravenous ketamine was not superior to midazolam in reducing depressive symptoms among inpatients with moderate to severe depression.

Abstract

Key Points Question For inpatients with moderate to severe depression, is repeated intravenous ketamine superior to a psychoactive placebo (midazolam) in reducing depressive symptoms? Findings In this randomized clinical trial, there was no statistically significant difference in the primary outcome, end-of-treatment Montgomery-Åsberg Depression Rating Scale score, between the ketamine and midazolam groups. No significant differences were observed on secondary efficacy, cognitive, economic, or quality-of-life outcomes. Meaning These findings do not support a superior antidepressant effect for serial intravenous ketamine infusions as an adjunctive therapy to usual inpatient care for moderate to severe depression.

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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