Spectral Changes of EEG Following a 6-Week Low-Dose Oral Ketamine Treatment in Adults With Major Depressive Disorder and Chronic Suicidality

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.

Keywords: EEG; depression; ketamine; spectral analysis; suicidality.

Figure 1.

Oral Ketamine Trial on Suicidality (OKTOS) design.

Figure 2.

Theta band power for different timepoints and brain regions. Power spectra values have been plotted in a logarithmic scale y-axis. Statistical significance annotations are as follows: *P < .05, **P < .01; exact P values can be found in supplementary Table 1.1.

Figure 3.

Alpha band power for different timepoints and brain regions. Power spectra values have been plotted in a logarithmic scale y-axis. Statistical significance annotations are as follows: *P < .05, **P < .01; exact P values can be found in supplementary Table 1.2.

Figure 4.

Low-beta band power for different timepoints and brain regions. Power spectra values have been plotted in a logarithmic scale y-axis. Statistical significance annotations are as follows: *P < .05; exact P values can be found in supplementary Table 1.3.

Figure 5.

High-beta band power for different timepoints and brain regions. Power spectra values have been plotted in a logarithmic scale y-axis. Statistical significance levels, that is, P values, can be found in supplementary Table 1.4.

Figure 6.

Theta at the occipital region between posttreatment and follow-up timepoints (also had significant change in power; see Figure 1) positively correlates with Depression Anxiety Stress Scale (DASS-S) (left) and for depression (DASS-D) (right). Displayed data are ranked and plotted in percentiles.

Figure 7.

Illustrative visualization of brain regions and significant changes in band powers between Pre-Post (left), Post-FUP (middle), and Pre-FUP (right) timepoints. Created with BioRender.com.