Mounting scientific evidence continues to dash once-high hopes that lithium can help people with amyotrophic lateral sclerosis. On April 6, a multicenter team of researchers reported online in the journal Lancet that their double-blind, placebo-controlled trial came up negative. Lead authors were Swati Aggarwal of the Massachusetts General Hospital in Boston and Lorne Dinman of the Sunnybrook Health Sciences Center in Toronto, Canada.

The trial was started in the wake of news that Italian researchers found impressive effects from lithium in mice and in a small human cohort (see ARF related news story on Fornai et al., 2008). Aggarwal and colleagues planned their study with a built-in interim analysis once 84 subjects had enrolled. At that time, in September of 2009, a National Institute of Neurological Disorders and Stroke panel decided that more subjects, or more time, would not yield the spectacular results the study was designed to discover. ARF first covered this development in our January round-up of clinical trials news in ALS (see ARF related news story).

The trial organizers used a design that is unusual in ALS trials. Because people with ALS could get lithium off-label (it is used to treat mania), and thus would be wary about landing in the placebo group, the scientists promised that placebo participants would be switched to lithium after their condition progressed by a certain amount. This design, with built-in interim analyses and crossover from placebo, is attractive for ALS trials, wrote Michael Swash of the Royal London Hospital in an accompanying commentary, because it allows researchers to obtain results quickly.


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News Citations

  1. Study Looks to Lithium for Treating ALS—Patients Follow Suit
  2. Clinical Trials for ALS: Taking Stock of 2009, Looking to 2010

Paper Citations

  1. . Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. PubMed.

Further Reading


  1. . A systematic study of brainstem motor nuclei in a mouse model of ALS, the effects of lithium. Neurobiol Dis. 2010 Feb;37(2):370-83. PubMed.
  2. . Autophagy, lithium, and amyotrophic lateral sclerosis. Muscle Nerve. 2009 Aug;40(2):173-94. PubMed.
  3. . Review of lithium effects on brain and blood. Cell Transplant. 2009;18(9):951-75. PubMed.
  4. . Looking at lithium: molecular moods and complex behaviour. Mol Interv. 2008 Oct;8(5):230-41. PubMed.
  5. . Concurrent administration of Neu2000 and lithium produces marked improvement of motor neuron survival, motor function, and mortality in a mouse model of amyotrophic lateral sclerosis. Mol Pharmacol. 2007 Apr;71(4):965-75. PubMed.
  6. . No benefit from chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using a standard mouse model of familial ALS. PLoS One. 2009 Aug 3;4(8):e6489. PubMed.

Primary Papers

  1. . Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 May;9(5):481-8. PubMed.
  2. . Lithium time-to-event trial in amyotrophic lateral sclerosis stops early for futility. Lancet Neurol. 2010 May;9(5):449-51. PubMed.