HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation Related Collections Huntington's disease Chorea All Clinical trials Clinical trials Randomized controlled (CONSORT agreement)

Tetrabenazine as antichorea therapy in Huntington disease

A randomized controlled trial

From the Clinical Trials Coordination Center, Department of Neurology, University of Rochester School of Medicine and Dentistry, NY.

Address correspondence and reprint requests to Dr Marshall, Clinical Trials Coordination Center, Department of Neurology, University of Rochester School of Medicine and Dentistry, 1359 Mt. Hope Ave., Suite 223, Rochester, NY 14620; e-mail: fred.marshall{at}ctcc.rochester.edu

Background: Tetrabenazine (TBZ) selectively depletes central monoamines by reversibly binding to the type 2 vesicular monoamine transporter. Open-label reports indicate TBZ is effective in treating chorea.

Objective: To examine the safety, efficacy, and dose tolerability of TBZ for treating chorea in Huntington disease (HD).

Methods: The authors randomized 84 ambulatory patients with HD to receive TBZ (n = 54) or placebo (n = 30) for 12 weeks. TBZ was increased over 7 weeks up to a maximum of 100 mg/day or until the desired antichoreic effect occurred or intolerable adverse effects supervened. The primary outcome was the change from baseline in the chorea score of the Unified Huntington's Disease Rating Scale (UHDRS)

Results: TBZ treatment resulted in a reduction of 5.0 units in chorea severity compared with a reduction of 1.5 units on placebo treatment (adjusted mean effect size = –3.5 ± 0.8 UHDRS units [mean ± SE]; 95% CI: –5.2, –1.9; p < 0.0001). There was also a significant benefit on ratings of clinical global improvement. There were five study withdrawals in the TBZ group and five serious adverse events (SAEs) in four subjects (drowning suicide, complicated fall, restlessness/suicidal ideation, and breast cancer) compared with one withdrawal and no SAEs in the placebo group.

Conclusion: Tetrabenazine (TBZ), at adjusted dosages of up to 100 mg/day, effectively lessens chorea in ambulatory patients with Huntington disease. TBZ should be dosed individually based on ongoing assessment of possible adverse side effects.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the February 14 issue to find the title link for this article.

*See the Appendix for a complete listing of authors.

Disclosure: This study was funded by a grant from Prestwick Pharmaceuticals, Inc., to the University of Rochester and in turn through subcontracts to the participating research sites. The Huntington Study Group (HSG) is a nonprofit consortium of Huntington's disease investigators (http://www.huntington-study-group.org/). None of the HSG investigators or staff had equity interests with Prestwick Pharmaceuticals, Inc. Dr. Fahn received consulting fees of less than $10,000. Dr. Marshall presented data at national meetings for which he received travel reimbursement from Prestwick Pharmaceuticals, Inc. Dr. Clarence-Smith, Dr. O'Brien, and Ms. Wilson are employees of Prestwick Pharmaceuticals, Inc. The HSG Coordination and Biostatistics Centers at the University of Rochester independently compiled and analyzed the data for this study.

Received April 4, 2005. Accepted in final form October 18, 2005.

Correspondence: