Tetrabenazine (Xenazine): Monoamine depleter approved for the treatment of chorea associated with Huntington's disease

Tetrabenazine is a reversible depleter of monoamines; this is believed to be the mechanism by which this agent exerts its antichorea effects. Tetrabenazine was approved on August 15, 2008, for the treatment of chorea associated with Huntington's disease (HD).

Efficacy. The efficacy of tetrabenazine was evaluated in a randomized, double-blind, placebo-controlled, multicenter trial. Patients were treated with tetrabenazine or placebo for 12 weeks. Tetrabenazine was initiated at a dose of 12.5 mg/d and was titrated at weekly intervals in 12.5-mg increments until control of chorea was achieved, side effects were intolerable, or a maximum dose of 100 mg/d was reached. The primary end point was change in total chorea score, which rates chorea on a scale from 0 (no chorea) to 4 for 7 different parts of the body (total scale, 0–28). Patients treated with tetrabenazine demonstrated an estimated decrease in total chorea score of 5.0 units during maintenance therapy versus an estimated decrease of 1.5 units in placebo-treated patients (treatment effect, –3.5 units; P<.05). In a second controlled study, patients who had been treated with open-label tetrabenazine for ≥2 months were randomized to continued treatment with tetrabenazine at the same dose or placebo for 3 days; chorea scores were then compared. The treatment effect was approximately –3.5 units in favor of tetrabenazine, although this difference did not reach statistical significance (P=.1).

Safety. HD is characterized by changes in mood, cognition, chorea, rigidity, and functional capacity. Tetrabenazine has been associated with a slight worsening in mood, cognition, rigidity, and functional capacity. Patients with HD are at an increased risk for depression and suicidal ideation/behavior; tetrabenazine increases these risks. Treatment with tetrabenazine has been associated with neuroleptic malignant syndrome. In clinical trials, tetrabenazine-treated patients demonstrated an increased incidence of akathisia compared with placebo-treated patients. Tetrabenazine has been associated with parkinsonism, sedation, postural dizziness, and a slight increase in the corrected QT (QTc) interval. Patients treated with neuroleptic drugs may develop a potentially irreversible syndrome of involuntary, dyskinetic movements. The most common adverse events associated with tetrabenazine treatment include sedation/somnolence, fatigue, insomnia, depression, akathisia, and nausea.