Clinical Effects of Continuous Theta Burst Stimulation for Generalized Anxiety Disorder and a Mechanism Involving Alpha Oscillations: A Randomized Controlled Trial

SOURCE: Journal of Psychiatry & Neuroscience. 47(2):E123-E133, 2022 Mar-Apr.

AUTHORS: Li X; Zhang C; Tan J; Ding L; Wang C; Wang M; Lin Y

BACKGROUND: Continuous theta burst stimulation (cTBS) is a much more rapid protocol than low-frequency repetitive transcranial magnetic stimulation (rTMS), but no clinical trial has yet investigated the efficacy and mechanisms of cTBS for the treatment of generalized anxiety disorder. The purpose of this study was to compare the clinical effects and alpha oscillations induced by cTBS versus 1 Hz rTMS as predictors of response, and to assess the underlying mechanisms of the therapeutic effects of cTBS in patients with generalized anxiety disorder.

METHODS: We randomly allocated 120 patients with generalized anxiety disorder to receive cTBS (n = 41), 1 Hz rTMS (n = 40) or sham cTBS (n = 39) over the right dorsolateral prefrontal cortex; we also included healthy controls (n = 30) to compare neurophysiological data. We analyzed changes in Hamilton Anxiety Rating Scale scores and alpha oscillations (frequency and power) at baseline, post-treatment and 1-month follow-up.

RESULTS: After 20 sessions of treatment, patients’ anxiety had improved and alpha power had increased in the cTBS and 1 Hz rTMS groups. However, at 1-month follow-up the cTBS group had significantly more responders and remitters, and higher alpha oscillations than the 1 Hz rTMS group (post hoc analysis: cTBS > rTMS > sham). At baseline, alpha frequency was inversely correlated with psychological symptom scores on the Hamilton Anxiety Rating Scale (r = -0.613, p < 0.001); post-treatment, this correlation was present only in the cTBS group (r = -0.685, p < 0.001).

LIMITATIONS: Electroencephalography data were limited to the alpha band.

CONCLUSION: Our findings provide evidence for the clinical use of cTBS, a novel brain stimulation protocol. Its therapeutic effects may be the result of increasing alpha frequency, thereby improving the psychological symptoms of generalized anxiety disorder.