Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To evaluate the efficacy and safety of memantine in patients with mild to moderate Alzheimer's disease (AD) receiving cholinesterase inhibitor (ChEI) treatment.


METHODS
Participants (N= 433) with probable AD, Mini-Mental State Exam (MMSE) scores between 10-22 (inclusive), and concurrent stable use of ChEIs (donepezil, rivastigmine, galantamine) were randomized to placebo or memantine (20 mg once daily) for 24 weeks. Primary outcomes were changes from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and on Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) score. Secondary measures comprised the 23-item Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL(23)), Neuropsychiatric Inventory (NPI), and MMSE.


RESULTS
At the end of the trial, there were no statistically significant differences between the memantine- and placebo group on primary and secondary outcome measures. The incidence of adverse events (AEs) was similar between the two groups, with no AE occurring in more than 5% of memantine-treated patients and at a rate twice that of the placebo group.


CONCLUSIONS
In this trial, memantine did not show an advantage over placebo based on protocol-specified primary or secondary analyses in patients with mild to moderate AD on stable ChEI regimens. There were no significant differences in tolerability and safety between the memantine- and placebo groups.
Porsteinsson
Anton P
AP
Alzheimer's Disease Care, Research and Education Program, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14620, USA. Anton_Porsteinsson@urmc.rochester.edu
Grossberg
George T
GT
Mintzer
Jacobo
J
Olin
Jason T
JT
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use*; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine