Esketamine disinhibits brain networks in depression: Evidence from oscillatory and aperiodic activity.
Progress in neuro-psychopharmacology & biological psychiatry July 5, 2025 Verina Guirguis, Sanvi Korsapathy, Francesca Pupillo et al. 6 citations
Nasal esketamine, a rapid-acting antidepressant, alters brain network activity by reducing top-down control and shifting the excitation/inhibition balance toward excitation. In eight individuals with major depressive disorder, EEG recordings before and up to 90 minutes after esketamine administration showed decreased frontoparietal alpha power and central beta power, along with increased frontal midline delta and low gamma power. The aperiodic exponent decreased, indicating cortical disinhibition. These neural changes correlated with increased subjective ratings of highness and happiness and decreased tension, linking the drug's neurophysiological effects to the immediate subjective experience.