Dosage Effects Of Riluzole In Huntington'S Disease - A Multicenter Placebo-Controlled Study

Background: Riluzole retards striatal glutamate release and pathologic consequences in neurotoxic animal models of Huntington's disease ( HD). Objective: To determine the dosage- related impact of riluzole on chorea in HD. Methods: An 8- week double- blind dose- ranging multicenter study of riluzole was conducted in 63 subjects ( 32 women, 31 men) with HD who were randomized to receive placebo, riluzole 100 mg/ day, or riluzole 200 mg/ day. The prespecified outcome measure was change in the total maximal chorea score of the Unified Huntington's Disease Rating Scale ( UHDRS). Results: Fifty- six ( 89%) subjects completed the study. A reduction ( p < 0.01) in chorea at 8 weeks was found using a linear trend test with dose. Comparing the groups individually, the reduction in chorea for the riluzole 200- mg/ day group ( - 2.2 +/- 3.3) was different ( p = 0.01) from placebo ( + 0.7 +/- 3.4), but the riluzole 100- mg/ day group ( - 0.2 +/- 2.9) was not. Riluzole did not improve other motor, cognitive, behavioral, or functional components of the UHDRS. Alanine aminotransferase was elevated in a dosage- dependent fashion ( p = 0.01). Conclusions: Over 8 weeks of treatment, riluzole 200 mg/ day ameliorated chorea intensity in HD without improving functional capacity or other clinical features of illness. Riluzole 200 mg/ day was attended by reversible liver transaminase abnormalities that would require monitoring in long- term studies.