A preliminary study of fMRI-Guided rTMS in the treatment of generalized anxiety disorder

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method that holds promise for treating several psychiatric disorders. Yet the most effective location and parameters for treatment need more exploration. Also, whether rTMS is an effective treatment for individuals with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not been empirically tested. The goal of this pilot study was to evaluate whether functional magnetic resonance imaging (fMRI)-guided rTMS is effective in reducing symptoms of GAD. Method: Ten participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program, and between the ages of 18 and 56 years were enrolled in the study from August 2006 to March 2007. A pretreatment symptom provocation fMRI experiment was used to determine the most active location in the prefrontal cortex of the participants. Ten participants completed 6 sessions of rTMS over the course of 3 weeks, stereotactically directed to the previously determined prefrontal location. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement of Illness (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of I or 2 ("very much improved" or "much improved," respectively). Results: Overall, rTMS was associated with significant decreases in HAM-A scores (t = 6.044, p = .001) indicative of clinical improvement in GAD symptoms. At endpoint, 6 (60%) of the 10 participants who completed the study showed reductions of 50% or more on the HAM-A and a CGI-I score of I or 2; those 6 subjects also had an endpoint HAM-A score < 8, therefore meeting criteria for remission. Conclusion: Results of the current study suggest that fMRI-guided rTMS treatment may be a beneficial technique for the treatment of anxiety disorders. Limitations include a small sample size and open-label design with a technology that may be associated with a large placebo response. These limitations necessitate further research to determine whether rTMS is indeed effective in treating anxiety disorders. Trial Registration: clinicaltrials.gov Identifier: NCT00539357.