Dosage effects of riluzole in Huntington’s disease

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Abstract
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.