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.
D002819:Chorea / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019782:Riluzole / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole