2013 Articles

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

Shen, Vivienne; Clarence-Smith, Kathleen; Hunter, Christine; Jankovic, Joseph

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 less than or equal to 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 greater than or equal to 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.