Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome

Abstract

Background: A small proportion of individuals with Tourette syndrome (TS) have a lifelong course of illness that fails to respond to conventional treatments. Open label studies have suggested that low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may be effective in reducing tic severity.

Objective/hypothesis: To examine the efficacy of rTMS over the SMA for TS in a randomized double-blind sham-controlled trial (RCT).

Methods: We conducted a two-site RCT-rTMS with 20 adults with severe TS for 3 weeks. Treatment consisted of 15 sessions (1-Hz; 30 min; 1800 pulses per day) of active or sham rTMS at 110% of the motor threshold over the SMA. A subsequent 3 week course of active rTMS treatment was offered.

Results: Of the 20 patients (16 males; mean age of 33.7 ± 12.2 years), 9 received active and 11 received sham rTMS. After 3 weeks, patients receiving active rTMS showed on average a 17.3% reduction in the YGTSS total tic score compared to a 13.2% reduction in those receiving sham rTMS, resulting in no statistically significant reduction in tic severity (P = 0.27). An additional 3 week open label active treatment for those patients (n = 7) initially randomized to active rTMS resulted in a significant overall 29.7% reduction in tic severity compared to baseline (P = 0.04).

Conclusion: This RCT did not demonstrate efficacy of 3-week SMA-targeted low frequency rTMS in the treatment of severe adult TS. Further studies using longer or alternative stimulation protocols are warranted.

Trial registration: ClinicalTrials.gov NCT00529308.

Keywords: Magnetic stimulation; Randomized controlled trial; Tourette syndrome; Transcranial.

Conflict of interest statement

Conflicts of interest:

Dr. Leckman has received support from the National Institutes of Health (salary and research funding R21MH082323, R01 HD070821, R01 MH61940, K05MH076273, T32 MH018268), Tourette Syndrome Association (research funding), United States- Israel Binational Science Foundation, Grifols, LLC (research funding [past]), John Wiley and Sons (book royalties), McGraw Hill (book royalties), Oxford University Press (book royalties), and the Rembrandt Foundation [past]). Dr. Lisanby reports having served as a principal investigator on industry-sponsored research grants to Columbia/RFMH or Duke (Neuronetics [past], Brainsway, ANS/St Jude Medical, Cyberonics [past], and NeoSync); equipment loans to Columbia or Duke (Magstim and MagVenture). She is a co-inventor on a patent application on TMS technology; is supported by grants from NIH (R01MH091083-01, 5U01MH084241-02, and 5R01MH060884-09), Stanley Medical Research Institute, and Brain & Behavior Research Foundation/NARSAD; and has no consultancies, speakers bureau memberships, board affiliations, or equity holdings in related device industries. Drs. Mantovani, Landeros-Weisenberger, Motlagh, Alvarenga, and Ms. Katsovich have no conflicts of interest or financial disclosures to report.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

Figure 1a. YGTSS Total Tic Score Change from Baseline to Week 3 during Double Blind Phase Figure 1b. YGTSS Total Tic Score Change from Week 3 to Week 6 during Open Label Phase Figure 1a and 1b: Figure 1a shows mean Yale Global Tic Severity Scale scores from baseline to week 3 during double blind phase. Figure 1b depicts Yale Global Tic Severity Scale scores from week 3 to week 6 when all patients received active treatment. At the end of 3 weeks (controlled blinded phase) completers showed a reduction of 17.3% with active and 13.2% with sham repetitive transcranial magnetic stimulation (rTMS) in tic severity scores (p=0.56). After a 3-week additional active rTMS patients initially randomized for active rTMS showed further improvement. The mean decrease in the YGTSS total tic severity score from Baseline (36.0 [10.2]) to 6 weeks (25.3 [6.7]) for these 7 individuals was significant (10.7 points [29.7%]; t=2.6, df=6, p=0.04).