No abstract

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.

No abstract

The anxiolytic activity and tolerance of four doses of suriclone (0.1, 0.2, 0.3 and 0.4 mg tid), diazepam (5 mg tid), and placebo were compared in six parallel groups of 54-59 outpatients with generalized anxiety disorder (DSM III-R). After a 1-week placebo run-in period, the patients were treated for 4 weeks, with assessments at baseline and after 1, 2, and 4 weeks by the Hamilton anxiety scale and the Clinical Global Impressions. Results showed better improvement with active drugs as compared to placebo, without significant differences among the four different doses of suriclone and diazepam. The number of adverse events, particularly drowsiness, was significantly higher with diazepam than with suriclone, particularly 0.1 and 0.2 mg tid which did not differ from placebo. These results demonstrate that suriclone at daily doses ranging from 0.1 to 0.4 mg tid is an effective anxiolytic, better tolerated than diazepam.