Safety and Efficacy of Tetrabenazine and Use of Concomitant Medications During Long-Term, Open-Label Treatment of Chorea Associated with Huntington's and Other Diseases

Background: Although tetrabenazine, a drug that depletes presynaptic dopamine by inhibiting vesicular monoamine transporter 2 (VMAT2), was approved by the U.S. Food and Drug Administration in 2008 for the treatment of chorea associated with Huntington's disease (HD), there is a paucity of data on its long-term efficacy and safety.

Methods: Approximately 2,000 patients with a variety of hyperkinetic movement disorders had been treated with open-label tetrabenazine at the Movement Disorders Clinic, Baylor College of Medicine, since 1979. Tetrabenazine was usually started at 12.5 mg/day, and the dosage was gradually increased (up to 300 mg/day). Responses were rated by the investigator 1-5, with 1 = marked chorea reduction, excellent improvement in function; 2 = moderate chorea reduction, very good improvement in function; 3 = fair chorea improvement, only mild improvement in function; 4 = poor or no response for chorea and function; and 5 = worsening chorea, some functional deterioration. Efficacy and safety were analyzed retrospectively.

Results: By 2004, 98 HD chorea patients had received tetrabenazine for a mean of 3.1 years (range ≤1-11.4 years). Of those with valid ratings, 75% had either marked or very good responses (rating 1 or 2) at their optimal dosages. The most common adverse events occurring in ≥5% of the patients were somnolence (39%), insomnia (33%), depression (31%), accidental injury (26%), and dysphagia (19%). Efficacy and safety were comparable to results for non-HD chorea patients.

Discussion: Tetrabenazine treatment was associated with long-term improvement in chorea. Adverse event rates were comparable to those reported from controlled trials.