a1 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
a2 McGill Centre for Studies in Aging, Alzheimer's Disease Research Unit, Montreal, Quebec, Canada
a3 Douglas Mental Health Research Institute, Montreal, Quebec, Canada
a4 H. Lundbeck A/S, Valby, Denmark
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.
(Received January 02 2013)
(Reviewed January 20 2013)
(Revised February 02 2013)
(Accepted February 05 2013)
(Online publication March 08 2013)
c1 Correspondence should be addressed to: Dr Nathan Herrmann, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, FG08, Toronto, Ontario M4N 3M5, Canada. Phone: +416-480-6133; Fax: +416-480-6022. Email: firstname.lastname@example.org.