Trial PaperDepressive DisordersSuicidalityMajor Depressive Disorder (MDD)Neuroimaging & Brain MeasuresHealthy VolunteersKetamine

Spectral changes of EEG following a 6-week low-dose oral ketamine treatment in adults with major depressive disorder and chronic suicidality

In adults with major depressive disorder and chronic suicidality, a 6‑week low‑dose oral ketamine regimen produced a transient reduction in centro‑parietal alpha power immediately post‑treatment that returned toward baseline by four‑week follow‑up, while theta and low‑beta bands showed delayed changes emerging after treatment cessation. Decreases in occipital theta correlated with improvements in depression and stress scores, suggesting EEG spectral shifts may track clinical response.

Authors

  • Jim Lagopoulos

Published

International Journal of Neuropsychopharmacology
individual Study

Abstract

Background

Ketamine has considerable therapeutic potential in alleviating major depressive disorder and chronic suicidality. However, the clinical diagnosis of neuropsychiatric disorders requires more robust diagnostic criteria. Electroencephalography (EEG) has shown promise in classifying depressive and suicidal patients from healthy individuals. The present study aimed to identify changes in the spectral properties of EEG in patients with major depressive disorder and chronic suicidality after completing the 6-week Oral Ketamine Trial on Suicidality with follow-up occurring 4 weeks after final ketamine treatment and determine associations between EEG spectral output and clinical symptoms.

Methods

Participants (n = 25) had 4-minute eyes closed resting state EEG recorded at frontal, temporal, centro-parietal, and occipital regions. Spectral analysis was performed with Welch’s power spectrum density method, and the power of 4 distinct frequency bands was analyzed: theta, alpha, low-beta, and high-beta. Correlation analyses between changes in clinical symptoms and spectral power were conducted using Spearman’s ranked correlation.

Results

Between pre- and posttreatment, only centro-parietal alpha power decreased. Between posttreatment and follow-up, centro-parietal alpha increased again in addition to increases in temporal alpha, centro-parietal and temporal theta, and occipital low-beta and decreases in occipital theta and temporal low-beta. Additionally, the decrease of occipital theta positively correlated with clinical subscales for depression and stress.

Conclusions

EEG spectral analysis revealed significant changes in theta, alpha, and low-beta frequency bands. Alpha band showed initial changes after treatment; however, this trended back toward baseline levels after the treatment cessation. In contrast, theta and low-beta showed significant power changes only after the treatment had ended.

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Research Summary of 'Spectral changes of EEG following a 6-week low-dose oral ketamine treatment in adults with major depressive disorder and chronic suicidality'

Introduction

Major depressive disorder (MDD) is highly prevalent and a leading contributor to suicide risk, yet clinical diagnosis and prognosis still rely largely on symptom reports and clinical screening. To improve objective characterisation of MDD and suicidality, prior research has explored neurophysiological biomarkers. Electroencephalography (EEG) — especially spectral (frequency-band) analysis of resting-state signals — has shown promise for distinguishing depressed or suicidal individuals from healthy controls and for tracking effects of antidepressant interventions, including ketamine. This study aimed to characterise changes in EEG spectral power following a 6-week course of low-dose oral ketamine in adults with MDD and chronic suicidality, and to test whether EEG changes associate with clinical outcomes. Based on earlier ketamine-EEG work, the investigators hypothesised that at the end of treatment (Post) versus baseline (Pre) there would be: i) decreased theta power across regions, ii) decreased alpha power in the centro-parietal region, and iii) decreased low- and/or high-beta power in the centro-parietal region; they further predicted that at 4-week follow-up (FUP) EEG power would trend back towards pre-treatment values alongside clinical measures.

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