RTMS for Adults with Severe Tourette Syndrome

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DESCRIPTION (provided by applicant): Tourette syndrome (TS) and related neuropsychiatric conditions affect as many as 0.3 -1% of the population. They are chronic, relapsing disorders that can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond to the available treatments or experience intolerable side effects. Most of the widely used interventions result in at best a 30 to 40% reduction in tic severity. Although the etiology of TS is unknown, emerging knowledge concerning the underlying neurocircuitry has been used to guide the design of focal brain stimulation strategies to study and treat tic disorders. Transcranial magnetic stimulation (TMS) has been used to investigate TS for the past decade and repetitive TMS (rTMS) has been used as an investigational intervention for severe TS for at least the last five years. Initial rTMS studies targeting motor and premotor cortical sites with either 1 Hz or 15 Hz have had limited or no success in treating individuals with severe TS. However, the recent study by Mantovani et al. (2006) which targeted the Supplementary Motor Area (SMA) was the first to demonstrate that 1 Hz rTMS produced clinically significant improvement (67% reduction in tic severity) in five patients with TS. Two of these patients experienced a complete remission of their tic symptoms. These improvements were maintained for three months. This was an open study in which patients were treated five days a week for two weeks, for a total of 10 treatments. No major side effects were noted during the course of treatment or the subsequent three months. This Phase II clinical trial proposes to replicate the Mantovani et al. (2006) study using a sham stimulation control condition. We anticipate screening 50 patients and selecting 30 patients to participate in a randomized clinical trial (15 randomized to sham and 15 to active rTMS). Two sites will administer rTMS, Yale and Columbia. We will monitor the effects of these interventions using a blind, independent evaluator. This pilot/feasibility study will allow us to make accurate power estimates for a subsequent R01 to test the efficacy and side effects of rTMS to the SMA in a larger sample, and to examine side effects, secondary electrophysiological outcomes (paired-pulse TMS to measure the excitability of the motor cortex), secondary clinical outcomes (obsessive-compulsive symptoms, depressive symptoms, and attention deficit hyperactivity disorder symptoms), and the relative impact of concurrently administered medications.