Current issues of ACP Journal Club are published in Annals of Internal Medicine


Riluzole increased survival in amyotrophic lateral sclerosis

ACP J Club. 1994 July-Aug;121:9. doi:10.7326/ACPJC-1994-121-1-009

Source Citation

Bensimon G, Lacomblez L, Meininger V, and The ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med. 1994 Mar 3;330:585-91.



To determine if riluzole improves survival and functional status in patients with amyotrophic lateral sclerosis (ALS).


21-month randomized, double-blind, placebo-controlled trial.


7 tertiary care centers in France.


155 eligible patients with ALS, 20 to 75 years of age (mean age 57 y, 59% men). Exclusion criteria were signs of conduction block of motor nerves, sensory nerves, or both on electromyography; paraproteinemia on immunoelectrophoresis; substantial lesions on computed tomography or magnetic resonance imaging; indications of dementia; onset of first symptom ≥ 5 years previously; forced vital capacity ≤ 60% of the expected value; previous tracheostomy; hepatic or renal dysfunction; or pregnancy. Follow-up was 100% for survival and 80% for functional status outcomes.


Patients were stratified by center and site of onset of disease (limb or bulbar region) and randomly assigned to receive riluzole, 100 mg/d (n = 77), or placebo (n = 78).

Main outcome measures

Survival rate determined by death or tracheostomy and functional status assessed by a 4-point rating score with subscores for limb and bulbar function, clinical examination, and patient-reported symptoms. Patients were examined every 2 months.

Main results

Analysis was done on an intention-to-treat basis. Survival rates at 12 and 21 months were greater in the patients receiving riluzole compared with patients receiving placebo (P = 0.014 and P = 0.046, respectively) (Table). Survival was also greater among patients with bulbar-onset disease at 12 months (P = 0.014) and 24 months (P = 0.013); no difference existed in survival for patients with limb-onset disease (P = 0.17 and P = 0.355 at 12 and 21 mo) (Table). The annual rate of deterioration of muscle strength was slower in patients receiving riluzole compared with patients receiving placebo (23% vs 34%, P = 0.028). 19 patients in the riluzole group and 9 patients in the placebo group withdrew from the study because of adverse experiences.


Riluzole improved survival in patients with amyotrophic lateral sclerosis and slowed the rate of deterioration in 1 measure of functional status. The effect on survival was greatest in patients with bulbar-onset disease.

Source of funding: Rhône-Poulenc Rorer.

For article reprint: Dr. V. Meininger, Centre SLA, Hôtel-Dieu de Paris, 1, rue de la Cité, 75004 Paris, France. FAX 33-143-540-568.

Table. Riluzole vs placebo for amyotrophic lateral sclerosis*

Death at 12 mo Riluzole Placebo RRR (95% CI) NNT (CI)
All patients 26% 42% 39% (4 to 61) 7 (4 to 75)
Patients with bulbar-onset disease 27% 65% 59% (7 to 84) 3 (2 to 35)
Patients with limb-onset disease 36% 26% 40% (-18 to 140) Not significant
Death at 21 mo RRR (CI) NNT
All patients 51% 63% 19% (-6.3 to 40) Not significant
Patients with bulbar-onset disease 47% 82% 43% (4.2 to 71) 3 (2 to 45)
Patients with limb-onset disease 52%0 57% 10% (-25 to 35) Not significant

*Abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article.


Bensimon and colleagues report therapeutic benefits of riluzole in ALS. The drug reduced mortality and improved muscle strength. Patients with bulbar-onset ALS had the most favorable results, but patients with limb-onset ALS also improved.

Randomization balanced many potentially confounding variables between the placebo and riluzole groups. No differences were noted between patients taking placebo and those taking riluzole in many baseline characteristics known to affect outcome. Dysphagia, respiratory function, and rate of decline were, by chance, slightly worse in the 17 patients with bulbar ALS assigned to placebo (1). Rowland cautions that most of the positive result could derive from the 15 patients with bulbar-onset ALS who were treated with riluzole (1).

Patients with bulbar-onset ALS are distinguished from patients with limb-onset ALS by greater dysphagia, respiratory compromise, and higher mortality. Detection of an effect is easier when the base rate (e.g., for mortality) is higher, all other factors being equal. Respiratory events are more frequent in the bulbar ALS group, and any improvement in muscle strength may be expected to reduce respiratory fatalities. Muscle strength was improved in the overall sample, using the conservative intention-to-treat analysis. Improved muscle strength in the bulbar and respiratory musculature may account for the improved survival in patients with bulbar ALS. Unfortunately, the causes of death were not provided.

The release of riluzole probably will be pursued quickly because patients with ALS who take riluzole may derive benefit, and no other effective alternative is currently available. Whether the findings substantially alter clinical practice will depend on patient and clinician perceptions gained through experience with the drug and on further trials to fully assess its effectiveness.

John R. Absher, MD
Bowman Gray School of MedicineWinston-Salem, North Carolina, USA


1. Rowland LP. Riluzole for the treatment of amyotrophic lateral sclerosis—too soon to tell (Editorial)? N Engl J Med. 1994;330:636-7.