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

J Cohen, AC Reichelt, R Zamyadi, G Roberts, S Hardy, B Fernandes, SG Rhind, EC Lewis, V Bhat, M Palner, R Jetly, BT Dunkley

medRxiv Preprint Server February 25, 2025 preprint DOI: 10.1101/2025.02.25.25322463 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case study Longitudinal Case report
Sample size 1
Population Adult male with moderate-severe generalized anxiety disorder and depressive symptoms
Intervention Ketamine-assisted psychotherapy
Duration 4 of 6 sessions of ketamine administration and 2 integration sessions (part of a protocol of six KAP sessions and four integration sessions)
Topics Neuroplasticity Anxiety Esketamine Ketamine Psychedelic-assisted therapy
Keywords Ketamine therapy Mental health
Citations 1
Key findings Ketamine-assisted psychotherapy was associated with increased functional connectivity in four of five brain networks, increased beta activity, decreased theta oscillations, and reductions in anxiety and depression scores.

Abstract

This detailed case report explores the application of ketamine-assisted psychotherapy (KAP) in the treatment of a male patient in their late 30’s 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.

Comparable studies

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Study Year Design Participants
Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. Adolescents aged 14–19 with comorbid psychiatric diagnoses including... 2023 Case series n = 4
Case report: Adult with bipolar disorder and autism treated with ketamine assisted psychotherapy. A 29-year-old man with bipolar disorder, Autism Spectrum Disorder, and type 2 diabetes 2024 Case study n = 1
Reconnecting through dissociation: a 5-month follow-up case study on ketamine-assisted psychotherapy for anorexia nervosa. Female patient in her late twenties with anorexia nervosa and comorbid depression 2025 Case report n = 1
Ketamine-Assisted Psychotherapy for Treatment of Co-occurring Borderline Personality Disorder and Depression: A Case Study. A patient with co-occurring borderline personality disorder and depression 2025 Case study n = 1
Qualitative analysis of a patient's experience of ketamine-assisted psychotherapy for substance use disorder: Empirical synergies with twelve-step programs 28-year-old female treated for alcohol and opioid use disorder 2025 Case study n = 1

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