title: Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD.
  
  
  METHODS
  We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00545974.
  
  
  RESULTS
  Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients' preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one).
  
  
  CONCLUSIONS
  Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD.
  
  
  BACKGROUND
  Forest Research Institute.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. aboxer@memory.ucsf.edu
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Kaufer
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Chiadi
authors.initials: C
authors.lastname: Onyike
authors.forename: Neill
authors.initials: N
authors.lastname: Graf-Radford
authors.forename: Mario
authors.initials: M
authors.lastname: Mendez
authors.forename: Diana
authors.initials: D
authors.lastname: Kerwin
authors.forename: Alan
authors.initials: A
authors.lastname: Lerner
authors.forename: Chuang-Kuo
authors.initials: CK
authors.lastname: Wu
authors.forename: Mary
authors.initials: M
authors.lastname: Koestler
authors.forename: Jill
authors.initials: J
authors.lastname: Shapira
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sullivan
authors.forename: Kristen
authors.initials: K
authors.lastname: Klepac
authors.forename: Kristine
authors.initials: K
authors.lastname: Lipowski
authors.forename: Jerin
authors.initials: J
authors.lastname: Ullah
authors.forename: Scott
authors.initials: S
authors.lastname: Fields
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Merrilees
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.forename: M Marsel
authors.initials: MM
authors.lastname: Mesulam
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D057174:Frontotemporal Lobar Degeneration / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine