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Ketamine's Influence on Magnetoencephalography Patterns During a Working Memory Task in Treatment-Resistant Depression: An Exploratory Study.

Adam Fijtman, Mani Yavi, Abigail Vogeley, Dede Greenstein, Jessica R. Gilbert, Carlos A. Zarate

Bipolar Disorders April 2, 2025 DOI: 10.1111/bdi.70027 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Crossover trial Peer reviewed
Sample size 21
Population Individuals with treatment-resistant depression (14 with bipolar disorder, 7 with major depressive disorder)
Interventions Ketamine placebo (normal saline)
Duration 6 to 9 h after infusion
Topics Depression Ketamine Esketamine
Keywords Bipolar disorder Cognition Magnetoencephalography Treatment‐resistant depression Working memory Ketamine therapy Treatment-resistant depression trd Brain activity patterns Cognitive function Antidepressant mechanisms
Citations 2
Key findings Ketamine significantly improved depressive symptoms but had no effect on working memory, attention, or concentration, while inducing distinct gamma power changes in brain regions linked to attention and working memory.

Abstract

Treatment-resistant depression (TRD) remains a challenge, necessitating novel interventions that address associated cognitive deficits. The glutamatergic modulator ketamine exerts rapid antidepressant effects, prompting investigators to assess its impact on cognitive function, specifically working memory. This study explored ketamine's influence on working memory and magnetoencephalography (MEG) patterns during a working memory task in individuals with TRD. To examine the effects of ketamine on working memory, attention, and concentration, and to study MEG patterns during a working memory task in individuals with TRD. Twenty-one individuals with TRD (14 with bipolar disorder, 7 with major depressive disorder) received ketamine and placebo infusions in a crossover trial. Behavioral and MEG data were collected at baseline and 6 to 9 h after ketamine and placebo (normal saline) infusion. Working memory, attention, and concentration were assessed with the N-back task. Ketamine significantly improved depressive symptoms but had no effect on cognitive performance. MEG revealed increased gamma power in the parieto-occipital junction coupled with decreased gamma power in the posterior superior temporal sulcus and inferior frontal gyrus after ketamine administration compared to placebo. Despite robust antidepressant effects, ketamine did not affect working memory, attention, or concentration. However, distinct gamma power changes in brain regions linked to attention and working memory highlight the need to further explore the neurobiological mechanisms underlying ketamine's cognitive effects in TRD. Future research with larger samples, broader cognitive batteries, and repeated ketamine infusions are needed to fully elucidate ketamine's cognitive effects in individuals with TRD.

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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