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Original Investigation
July 10, 2017

Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea

Author Affiliations
  • 1Department of Neurology, Harvard Medical School, Boston, Massachusetts
  • 2Teva Pharmaceutical Industries, Frazer, Pennsylvania
  • 3Clinical Trials Coordination Center, University of Rochester, Rochester, New York
  • 4Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
  • 5Department of Neurology, Cooper University Hospital, Camden, New Jersey
  • 6CSD Biostatistics, Tucson, Arizona
  • 7Department of Neurology, University of Cincinnati, Cincinnati, Ohio
  • 8The Center for Neurologic Health, Toledo, Ohio
  • 9Department of Neurology, The University of Texas Medical School, Houston
  • 10South Shore Neurologic Associates, Islip, New York
  • 11Department of Neurology, Baylor College of Medicine, Houston, Texas
  • 12Department of Neurology, The Ohio State University, Columbus
  • 13Rocky Mountain Movement Disorders Center, Englewood, Colorado
  • 14Department of Neurology, University of Sydney, Sydney, Australia
  • 16Department of Statistics, University of Rochester, Rochester, New York
  • 17Department of Neurology, Duke University, Durham, North Carolina
  • 18Department of Neurology, University of Alabama School of Medicine, Birmingham
  • 19Department of Neurology, Medical University of South Carolina, Charleston
  • 20Department of Neurology, Virginia Commonwealth University, Richmond
JAMA Neurol. Published online July 10, 2017. doi:10.1001/jamaneurol.2017.1352
Key Points

Question  Is overnight treatment conversion from tetrabenazine to deutetrabenazine safe in patients with Huntington disease?

Findings  In this open-label, single-arm study, 37 patients with chorea associated with Huntington disease switched overnight from a stable, therapeutic tetrabenazine regimen to deutetrabenazine. Deutetrabenazine was generally safe and well tolerated, with chorea scores maintained at the end of week 1 of deutetrabenazine therapy and improved at week 8.

Meaning  Chorea control may be safely maintained after an overnight switch from tetrabenazine to deutetrabenzine.


Importance  Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.

Objectives  To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

Design, Setting, and Participants  In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control.

Interventions  Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen.

Main Outcomes and Measures  Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington’s Disease Rating Scale total maximal chorea score and total motor score were efficacy end points.

Results  Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001).

Conclusions and Relevance  In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.