title: Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial.
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.
  
  
  METHODS
  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.
authors: Department of Neuroscience, via Cherasco 15, 10126 Torino, Italy. achio@usa.net
authors: A
authors: A
authors: Chiò
authors: G
authors: G
authors: Borghero
authors: A
authors: A
authors: Calvo
authors: M
authors: M
authors: Capasso
authors: C
authors: C
authors: Caponnetto
authors: M
authors: M
authors: Corbo
authors: F
authors: F
authors: Giannini
authors: G
authors: G
authors: Logroscino
authors: J
authors: J
authors: Mandrioli
authors: N
authors: N
authors: Marcello
authors: L
authors: L
authors: Mazzini
authors: C
authors: C
authors: Moglia
authors: M R
authors: MR
authors: Monsurrò
authors: G
authors: G
authors: Mora
authors: F
authors: F
authors: Patti
authors: M
authors: M
authors: Perini
authors: V
authors: V
authors: Pietrini
authors: F
authors: F
authors: Pisano
authors: E
authors: E
authors: Pupillo
authors: M
authors: M
authors: Sabatelli
authors: F
authors: F
authors: Salvi
authors: V
authors: V
authors: Silani
authors: I L
authors: IL
authors: Simone
authors: G
authors: G
authors: Sorarù
authors: M R
authors: MR
authors: Tola
authors: P
authors: P
authors: Volanti
authors: E
authors: E
authors: Beghi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D016651:Lithium Carbonate / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D016651:Lithium Carbonate