title: A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease.
abstract: BACKGROUND
  Agitation and aggression in Alzheimer's disease (AD) are amongst the most serious of neuropsychiatric symptoms, and contribute to poor outcomes and worse quality of life. Previous studies have suggested a benefit for memantine on agitation and aggression, but none have examined its efficacy in community-dwelling patients with significant agitation and aggression at baseline, utilizing these behaviors as a primary outcome measure.
  
  
  METHODS
  Patients with moderate-to-severe AD with Neuropsychiatric Inventory (NPI) total score ≥13 and NPI agitation/aggression score ≥1 were randomized to placebo or 20-mg memantine in a double-blind, 24-week trial. Co-primary outcome measures were behavior, measured by total NPI score, and cognition, using the Severe Impairment Battery (SIB). Secondary outcome measures included global assessment, function and other measures of behavior. This trial was registered as Clinicaltrials.gov: NCT00857649.
  
  
  RESULTS
  A total of 369 patients (average age = 75, average MMSE = 12) were randomized to placebo or memantine. The study was prematurely terminated due to recruitment problems. There were no statistically significant differences between memantine and placebo in mean change from baseline in NPI, SIB, or any of the secondary outcome measures. Behavior improved in both groups (total NPI change scores -3.90 ± 1.24 for memantine and -5.13 ± 1.23 for placebo). Memantine was generally well tolerated and patient retention in both treatment arms was good.
  
  
  CONCLUSIONS
  The study failed to show the superiority of memantine in this sample of patients with moderate-to-severe AD with significant baseline agitation and aggression. Methodological limitations could have contributed to these results.
authors.affiliation: Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5, Canada. nathan.herrmann@sunnybrook.ca
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Neli
authors.initials: N
authors.lastname: Boneva
authors.forename: Ole Michael
authors.initials: OM
authors.lastname: Lemming
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects / Q000523:psychology*; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011595:Psychomotor Agitation / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D008559:Memantine