Tetrabenazine

Abstract

Oral tetrabenazine is currently the only drug approved by the US FDA for the treatment of chorea associated with Huntington's disease (HD). Although the precise antichorea mechanism of action is unknown, it most likely involves reversible depletion of monoamines, particularly dopamine, from presynaptic terminals via inhibition of human vesicular monoamine transporter type 2. In a 12-week, double-blind, placebo-controlled trial conducted in the US in patients with HD, oral tetrabenazine (≤100 mg/day; n = 54) was significantly (p = 0.0001) more efficacious than placebo (n = 30) at improving adjusted mean Unified HD Rating Scale (UHDRS) total maximum chorea scores (reduced from baseline by 5 vs 1.5) [primary endpoint]. After 12 weeks, improvements in UHDRS total maximum chorea scores of >3 were achieved by significantly (p < 0.0001) more patients in the tetrabenazine group than in the placebo group. The antichorea efficacy of tetrabenazine was maintained in an 80-week extension study (n = 75), with the adjusted mean UHDRS total maximum chorea score significantly (p < 0.001) reduced from baseline (score of 14.9) by 4.6 points (primary outcome). In the 12-week trial and 80-week extension study, treatment-emergent adverse events in the tetrabenazine group mainly occurred during the dosage-titration phase, a period during which the dosage was individually optimized. Most of these events were mild to moderate and were manageable with dosage adjustments or discontinuation of study drug.