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)
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.
Citations in the library
Cites 14
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- 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) The International Journal of Neuropsychopharmacology July 9, 2019
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. Journal of Affective Disorders November 1, 2020
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
and 9 more in the library