The role of frontal EEG in predicting clinical response of major depressive disorder to intranasal ketamine and esketamine.
Carlos Trenado, Erich Seifritz, Sebastian Olbrich, Stefano Ferrea
Journal of Affective Disorders November 22, 2025 DOI: 10.1016/j.jad.2025.120751 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective study Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Patients affected by major depressive disorder treated with esketamine or ketamine |
| Interventions | esketamine ketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | EEG Biomarker Entropy Functional connectivity Rapid-acting depression treatments Distinct brain signals |
| Citations | 4 |
| Key points | Increased frontal functional connectivity and decreased entropy in theta-band EEG before treatment predicted antidepressant response to (es)ketamine in major depressive disorder. |
Abstract
Ketamine and its enantiomer esketamine are NMDA receptor antagonists that have shown consistent antidepressant effects in major depression disorder (MDD). These effects suggest an active role of glutamate in the pathophysiology of depression. It has been hypothesized that acute increase of glutamate neurotransmission in the prefrontal cortex following treatment with (es)ketamine leads to synaptic plasticity and neurotrophic changes with following influence on theta activity of encephalography (EEG). The present retrospective study included a total of 43 patients affected by MDD and treated with either esketamine or ketamine. EEG recordings before treatment were related to clinical outcome as measured by both a self-rating and a rater-based psychometric scale. EEG measures were considered as possible predictive biomarkers for responsivity of MDD to (es)ketamine. In particular, we utilized phase locking value (PLV), phase lag index (PLI), Renyi and Tsallis entropy, as well as aperiodic spectral parameters (offset and decay exponent) by focusing on the frontal region and theta band. We found increased functional connectivity (PLI and PLV) and decreased entropy in responders to (es)ketamine compared to non-responders. Although, we did not find a predictive effect of aperiodic spectral parameters, we observed decreased values in responders compared to non-responders. Our results emphasize the role of frontal EEG as possible biomarker [area under the ROC curve of 0.7065 (Renyi entropy), 0.7101 (Tsallis entropy) and 0.7283 (PLI)] in predicting antidepressant effects of (es)ketamine.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.