Background Amyotrophic lateral sclerosis is a progressive motorneuron disease for which there is no adequate treatment. Someresearch suggests that the excitatory amino acid neurotransmitterglutamate may be involved in the pathogenesis.
Methods To evaluate the efficacy and safety of the antiglutamateagent riluzole, we conducted a prospective, double-blind, placebo-controlledtrial in 155 outpatients with amyotrophic lateral sclerosis.The dose of riluzole was 100 mg per day. Randomization was stratifiedaccording to the site of disease onset (the bulbar region orthe limbs). The primary end points were survival and rates ofchange in functional status. The main secondary end point waschange in muscle strength. Analyses were undertaken after 12months of treatment and at the end of the placebo-controlledperiod (median follow-up, 573 days).
Results After 12 months, 45 of 78 patients (58 percent) in theplacebo group were still alive, as compared with 57 of 77 patients(74 percent) in the riluzole group (P = 0.014). For patientswith 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-yearsurvival was 64 percent and 74 percent, respectively (P = 0.17).The survival advantage 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-controlled period, but it remainedsignificant in the overall population (P = 0.046) as well asin the patients with bulbar-onset disease (18 percent [3 of17] vs. 53 percent [8 of 15], P = 0.013). The deteriorationof muscle strength was significantly slower in the riluzolegroup than in the placebo group (P = 0.028). Adverse reactionsto riluzole included asthenia, spasticity, and mild elevationsin aminotransferase levels. Twenty-seven patients in the riluzolegroup withdrew from the study, as compared with 17 in the placebogroup.
Conclusions The antiglutamate agent riluzole appears to slowthe progression of amyotrophic lateral sclerosis, and it mayimprove survival in patients with disease of bulbar onset.
Source Information
From the Department of Clinical Pharmacology, Hopital de la Pitie-Salpetriere (G.B., L.L.); and the Centre SLA, Hotel-Dieu de Paris (V.M.) -- both in Paris. The participants in the ALS/Riluzole Study Group are listed in the Appendix.
Address reprint requests to Dr. Meininger at the Centre SLA, Hotel-Dieu de Paris, 1, rue de la Cite, 75004 Paris, France.
Riluzole in Amyotrophic Lateral Sclerosis
McKee P., Fuller G. N., Stevens D. L., MacRae K. D., Burgerman R. S., Rogawski M. A., Murphy J. R., Bensimon G., Lacomblez L., Meininger V., Rowland L. P., Caillard C.G., Louvel E., Randle J.C.R.
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N Engl J Med 1994;
331:272-274, Jul 28, 1994.
Correspondence
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