Ketamine-Assisted Psychotherapy for Generalized Anxiety Disorder: A Comprehensive Case Report with Integrated Neurophysiological Imaging Using Magnetoencephalography

This detailed case report explores the application of ketamine-assisted psychotherapy (KAP) in the treatment of a male patient in their late 30s with Generalized Anxiety Disorder (GAD) and depressive symptoms. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine represents a significant breakthrough in the treatment of mood and anxiety disorders due to its rapid and robust antidepressant effects. Preclinical studies demonstrate that ketamine promotes biological alterations in the brain, including enhancing neuroplasticity. However, no studies to date have examined the longitudinal effects of KAP using magnetoencephalography (MEG), a powerful functional neuroimaging modality. Resting state MEG (rsMEG) scanning allowed the exploration of the neural correlates of KAP-related changes in mood and anxiety symptoms, including the functional connectivity between brain networks involved in cognition and emotion regulation. In this case study, an adult male participant with moderate-severe GAD underwent two rsMEG scans and cognitive testing at baseline and after 4 of 6 sessions of a standard ketamine administration and 2 integration sessions, part of a protocol consisting of a total of six KAP sessions and four sessions of integration. We measured functional connectivity in 5 functional networks - default mode, attention, central executive, motor, and visual, as well as neural oscillatory activity. We saw functional connectivity increases in 4 of the 5 networks. This coincided with significant increases in cortical beta activity, a marker of inhibition, decrease in theta oscillations, reductions in GAD7 and PHQ9 scores, and improved attention. In summary, these findings emphasize the ability of rsMEG to detect KAP-induced brain network changes, offering a promising tool for identifying clinically relevant neural correlates that can both predict and monitor therapeutic outcomes via electrophysiological changes.