title: Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing.
abstract: BACKGROUND
  Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme.
  
  
  OBJECTIVE
  To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality.
  
  
  METHODS
  . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012).
  
  
  RESULTS
  To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect.
  
  
  CONCLUSIONS
  There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo.
authors.affiliation: Unidad de ELA, Servicio de Neurología, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, España. Electronic address: josepgamez.bcn@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Gamez
authors.affiliation: Unidad de ELA, Servicio de Neurología, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, España.
authors.forename: M
authors.initials: M
authors.lastname: Salvado
authors.affiliation: Unidad de ELA, Servicio de Neurología, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, España.
authors.forename: A
authors.initials: A
authors.lastname: Martínez de la Ossa
authors.affiliation: Unidad de ELA, Servicio de Neurología, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, España.
authors.forename: M
authors.initials: M
authors.lastname: Badia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D019782:Riluzole / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents; D019782:Riluzole
keywords: Amyotrophic lateral sclerosis; Clinical trial; Cochrane; Compassionate use; Ensayo clínico; Esclerosis lateral amiotrófica; Lithium; Litio; Uso compasivo