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) via PubMed
Summary
AI-generated from the abstractA higher percentage of EEG vigilance stage A1, a measure of brain activity, is associated with response to intravenous ketamine in major depression. In a phase-2 randomized controlled trial of oral prolonged-release ketamine for treatment-resistant depression, no significant interaction between response and treatment was found for this EEG marker. However, a small-scale meta-analysis showed a significant pooled mean difference between ketamine responders and non-responders. Applying a previously proposed A1 cutoff of 43% yielded chance-level prediction accuracy in the combined ketamine group but 75% accuracy in the 240 mg subgroup. Responders to 240 mg ketamine also showed more stable vigilance over time. These findings support EEG vigilance as a predictive biomarker for treatment outcomes in depression, though further validation is needed.
Study at a glance
| 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 |
| Keywords | Biomarkers biomarker Biological marker Molecular marker Brain Activity EEG |
| Citations | 2 |
| Key finding | 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.