The role of lithium in ALS remains unknown.

In a recent issue of The Lancet Neurology, Aggarwal et al. (1) reported a multicentric, randomized, double-blind, clinical trial comparing lithium carbonate plus riluzole with riluzole plus placebo in sporadic amyotrophic lateral sclerosis (ALS) with a time-to-event design in order to study lithium safety and effi cacy. The study was early fi nished because of a pre-specifi ed futility endpoint suggesting that lithium did not alter ALS progression. Since 1994, when the fi rst evidence of an effective treatment for ALS was published (2), many other clinical trials with different drugs and strategies were developed; none but riluzole produced signifi cant clinical improvements. A systematic review of riluzole treatment in ALS reported a small benefi t in favour of this medication on survival with a small effect on both bulbar and limb functions (3). In 2008, Fornai et al. (4) published the fi rst randomized clinical trial investigating lithium effects in ALS. This trial was developed after the demonstration of lithium effi cacy in a transgenic mouse model of motor neuron disease. Patients treated with lithium plus riluzole showed an increased survival and decreased disease progression rate measured by functional scores compared to patients treated only with riluzole. Although a small sample pilot study, this trial brought hope for ALS treatment together with concerns over the off-label use of lithium due to its availability and low cost. By conducting a larger, randomized, controlled clinical trial, Aggarwal et al. aimed to answer the question raised by Fornai et al. about lithium effi cacy in ALS; however, this study also presented important limitations. After two months of treatment