Clinical and biological changes under treatment with lithium carbonate and valproic acid in sporadic amyotrophic lateral sclerosis

J Neurol Sci. 2014 May 15;340(1-2):103-8. doi: 10.1016/j.jns.2014.03.005. Epub 2014 Mar 11.


The aim of this study was to evaluate the ability of lithium carbonate and valproate cotreatment to modify the survival rate and functional score of patients with definite sporadic amyotrophic lateral sclerosis (ALS). The clinical response of 18 enrolled patients was compared to the evolution of 31 ALS out-patients, carefully paired by age, gender, evolution rate and time of the disease, who never received treatment with lithium and/or valproate. The ALS functional rating scale, revised version (ALSFRS-R), was applied at baseline, 1 month, and every 4 months until the outcome (death or an adverse event). Biochemical markers, such as Cu/Zn superoxide dismutase and glutathione peroxidase activity, and reduced glutathione were assayed in plasma samples obtained at the baseline visit and after 5 and 9 months of treatment. Our results showed that lithium and valproate cotreatment significantly increased survival (p=0.016), and this treatment also exerted neuroprotection in our patients because all three markers reached levels that were not significantly different from the matched samples of healthy donors. The trial stopped after 21 months, when the sample was reduced to under two-thirds, due to the late adverse events of the treatment. The results call for large randomized clinical trials with the dual association, but at low doses to avoid adverse events.

Keywords: ALSFRS-R; Amyotrophic lateral sclerosis; Glutathione peroxidase; Lithium carbonate; Superoxide dismutase 1; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / mortality
  • Cadmium / blood
  • Cadmium / urine
  • Cause of Death
  • Disability Evaluation
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Lithium Carbonate / therapeutic use*
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Valproic Acid / therapeutic use*


  • Enzyme Inhibitors
  • SOD1 protein, human
  • Cadmium
  • Lithium Carbonate
  • Valproic Acid
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Glutathione