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Neurology. 2010 Aug 17;75(7):619-25. doi: 10.1212/WNL.0b013e3181ed9e7c. Epub 2010 Aug 11.

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

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  • 1Department of Neuroscience, via Cherasco 15, 10126 Torino, Italy. achio@usa.net

Abstract

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 (http://oss-sper-clin.agenziafarmaco.it/) (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.

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PMID:
20702794
[PubMed - indexed for MEDLINE]
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