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EEG vigilance and response to oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized validation study.

Anna Monn, Corinne Eicher, Annia Rüesch, Golo Kronenberg, Benjamin Offenhammer, Atalìa Adank, Mateo de Bardeci, Cheng-Teng Ip, Hanne Scherer, Linda Schaekel, Michael Colla, Annette B Brühl, Erich Seifritz, Sebastian Olbrich

Psychiatry research. Neuroimaging July 1, 2025 DOI: 10.1016/j.pscychresns.2025.112001 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 21
Population Patients with treatment-resistant depression
Intervention oral prolonged-release ketamine
Dose 240 mg
Topics Depression Ketamine Esketamine
Keywords Biomarkers biomarker Biological marker Molecular marker Brain Activity EEG Electroencephalogram Brainwaves Neural activity Ketamine-assisted therapy
Citations 2
Key findings EEG vigilance stage A1 percentage and stability may serve as predictive biomarkers for ketamine response in treatment-resistant depression, particularly at a 240 mg dose.

Abstract

Treatment-resistant depression (TRD) is associated with reduced quality of life and elevated mortality, posing a major challenge to psychiatric care. After non-response to conventional treatments, next-level interventions such as (es)ketamine are recommended, though remission rates remain variable. Identifying reliable markers of treatment response is therefore critical. Recent evidence suggests that a higher percentage of electroencephalography (EEG) vigilance stage A1 is associated with response to intravenous ketamine in major depression. We aimed to corroborate this finding in TRD patients from a recent phase-2 randomized controlled trial of oral prolonged-release ketamine. An algorithm classified vigilance stages in 21 10-minute resting-state EEG recordings. While no significant response × treatment interaction emerged for percentage of vigilance stage A1, a small-scale meta-analysis showed a significant pooled mean difference between ketamine responders and non-responders. Applying a previously proposed A1 cutoff (43 %) yielded chance-level prediction accuracy in the combined ketamine group, but 75 % accuracy in the 240 mg subgroup. Moreover, responders to 240 mg ketamine exhibited a significantly more stable vigilance over time compared to non-responders. Although further validation in a larger sample is warranted, these findings support the clinical value of EEG vigilance as a predictive biomarker for treatment outcomes in 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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