The role of frontal EEG in predicting clinical response of major depressive disorder to intranasal ketamine and esketamine

Nov 24, 2025Journal of affective disorders

Frontal brain activity predicting depression treatment response to nasal ketamine and esketamine

AI simplified

Psychedelic Science on OpenScience ↗PubMed ↗DOI ↗

Abstract

In a study of 43 patients with major depressive disorder, frontal EEG readings may help predict the effectiveness of esketamine or ketamine treatment.

Increased functional connectivity was observed in responders to (es)ketamine compared to non-responders.
Responders showed decreased entropy levels compared to non-responders.
The study found potential predictive biomarkers in EEG measures, particularly phase lag index (PLI) and entropy values.
Area under the ROC curve for Renyi entropy was 0.7065, for Tsallis entropy was 0.7101, and for PLI was 0.7283.
Findings suggest glutamate's role in depression may involve synaptic plasticity and changes in brain activity.

AI simplified

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 the 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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

The role of frontal EEG in predicting clinical response of major depressive disorder to intranasal ketamine and esketamine

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief