Lithium carbonate in amyotrophic lateral sclerosis: Lack of efficacy in a dose-finding trial

A. Chiò, G. Borghero, A. Calvo, M. Capasso, C. Caponnetto, M. Corbo, F. Giannini, G. Logroscino, J. Mandrioli, N. Marcello, L. Mazzini, C. Moglia, M. R. Monsurrò, G. Mora, F. Patti, M. Perini, V. Pietrini, F. Pisano, E. Pupillo, M. SabatelliF. Salvi, V. Silani, I. L. Simone, G. Sorarù, M. R. Tola, P. Volanti, E. Beghi

Research output: Contribution to journalArticlepeer-review


Background: A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). Methods: The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs ( (EudraCT number 2008-001094-15). Results: As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. Conclusions: Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. Classification of evidence: The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs.

Original languageEnglish
Pages (from-to)619-625
Number of pages7
Issue number7
Publication statusPublished - Aug 17 2010

ASJC Scopus subject areas

  • Clinical Neurology


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