A CONTROLLED TRIAL OF RILUZOLE IN AMYOTROPHIC-LATERAL-SCLEROSIS

Background. Amyotrophic lateral sclerosis is a progressive motor neuro n disease for which there is no adequate treatment. Some research sugg ests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis. Methods. To evaluate the efficacy and sa fety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotro phic lateral sclerosis. The dose of riluzole was 100 mg per day. Rando mization was stratified according to the site of disease onset (the bu lbar region or the limbs). The primary end points were survival and ra tes of change in functional status. The main secondary end point was c hange in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median foll ow-up, 573 days). Results. After 12 months, 45 of 78 patients (58 perc ent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014 ), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantag e with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlle d period, but it remained significant in the overall population (P = 0 .046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group. Conclusions. The antiglutama te agent riluzole appears to slow the progression of amyotrophic later al sclerosis, and it may improve survival in patients with disease of bulbar onset.