title: Memantine for fragile X-associated tremor/ataxia syndrome: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Memantine, an uncompetitive N-methyl-d-aspartate receptor antagonist, is currently approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. Anecdotal reports have suggested that memantine may improve neurologic and cognitive symptoms of individuals with the neurodegenerative disease fragile X-associated tremor/ataxia syndrome (FXTAS); however, its efficacy and safety in this population have not been assessed in a controlled trial.
  
  
  METHODS
  Individuals with FXTAS aged 34-80 years were enrolled in a randomized, double-blind, placebo-controlled, 1-year trial between September 2007 and August 2012. Inclusion required definite, probable, or possible FXTAS in clinical stages 1-5 according to previously published criteria. Primary outcome measures were the Behavioral Dyscontrol Scale (BDS) score and CATSYS intention tremor severity.
  
  
  RESULTS
  Ninety-four participants were randomized from 205 screened; of those, 43 and 45 started treatment with memantine (titrated to 10 mg twice daily) and placebo, respectively. Thirty-four participants receiving memantine and 36 receiving placebo completed the 1-year endpoint assessment (n = 70). Intention-to-treat analysis showed no improvement with respect to intention tremor severity (mean [SD] values with memantine vs placebo: 1.05 [0.73] vs 1.89 [2.19], P = .047) or BDS score (16.12 [5.43] vs 15.72 [3.93], P = .727) at follow-up. Post hoc analyses of participants with early FXTAS (stage ≤ 3), those with late FXTAS (stage > 3), and those in different age groups (≤ 65 years and > 65 years) also indicated no significant improvement. More frequent mild adverse events were observed in the placebo group, while more frequent moderate adverse events occurred in the memantine group (P = .007).
  
  
  CONCLUSIONS
  This randomized, double-blind, placebo-controlled trial of memantine for individuals with FXTAS showed no benefit compared to placebo with respect to the selected outcome measures.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00584948.
authors.affiliation: 2230 Stockton Blvd, Sacramento, CA 95817 andreea.seritan@ucdmc.ucdavis.edu.
authors.forename: Andreea L
authors.initials: AL
authors.lastname: Seritan
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
authors.forename: Yi
authors.initials: Y
authors.lastname: Mu
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: James A
authors.initials: JA
authors.lastname: Bourgeois
authors.forename: Andrea
authors.initials: A
authors.lastname: Schneider
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Cogswell
authors.forename: Kylee R
authors.initials: KR
authors.lastname: Cook
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Leehey
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.forename: John M
authors.initials: JM
authors.lastname: Olichney
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Adams
authors.forename: Wendi
authors.initials: W
authors.lastname: Legg
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001259:Ataxia / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014202:Tremor / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D010919:Placebos; D008559:Memantine