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Study does not support adding lithium to riluzole to slow disease progression in ALS

Wednesday, May 12 2010 | Comments

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What's This? Adding lithium carbonate to riluzole does not slow disease progression in amyotrophic lateral sclerosis (ALS) more than riluzole alone does, according to findings from a double-blind trial conducted in the United States and Canada.

According to the study authors, previous research from a pilot trial conducted in Italy suggested that the addition of lithium to riluzole slowed neurologic decline. The current trial was designed to confirm or refute the findings from this pilot trial.

The study included patients with ALS who had been taking a stable dose of riluzole for >=30 days. The participants were randomized to receive additional treatment with lithium or placebo, with lithium doses titrated to match those of the Italian study (0.4 mEq/L to 0.8 mEq/L). The trial was designed to include 250 patients. The current findings reflect results of the first planned interim analysis, which was conducted after 84 patients had been assigned to treatment.

The primary outcome was time to an event, defined as a decrease of >=6 points in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score or death.

Results of the interim analysis showed that 22 of 40 patients in the lithium group experienced a primary outcome event, compared with 20 of 44 patients in the placebo group who did so (P=.51). The hazard ratio for reaching the primary endpoint was 1.13 (95% CI, 0.61-2.07).

In an analysis that tested the superiority of lithium, the study criterion for futility was met (P>=0.68), and the trial was stopped after a mean follow-up period of 5.4 months.

There were also no significant differences between lithium and placebo in secondary endpoint assessments, including the mean changes in ALSFRS-R scores, slow vital capacity, and self-reported depressive symptoms.

There were no major safety concerns during the trial. Adverse events that were more common with lithium than with placebo included falls (P=.04) and back pain (P=.05).

The study authors said they could not exclude the possibilities that lithium might have had a small positive effect, that other serum levels might be beneficial, or that a small benefit might have been observed if more patients had received therapeutic levels of the drug for longer periods of time.

However, they concluded that there currently remains "no convincing evidence for the use of lithium as a treatment for patients with ALS." (Aggarwal SP, et al. Lancet Neurol 2010;9:481-488.)

This information concerns a use that has not been approved by the Food and Drug Administration.

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