A 24-week Randomized, Controlled Trial of Memantine in Patients With Moderate-to-severe Alzheimer Disease

Abstract

This study examined the efficacy and safety of memantine monotherapy in patients with moderate-to-severe Alzheimer disease (AD). Patients not receiving a cholinesterase inhibitor (N=350) were randomized to receive memantine (20 mg/d) or placebo during this 24-week, double-blind, placebo-controlled trial. Prospectively defined analyses failed to demonstrate a statistically significant benefit of memantine treatment compared with placebo on the Severe Impairment Battery (SIB) at week 24 end point, although a significant advantage was observed for memantine at weeks 12 and 18. The 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL19) did not differ significantly between groups in any analysis. Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-Plus) did not significantly favor memantine at week 24 despite a significant advantage for memantine at weeks 12 and 18. Other secondary outcomes showed no significant treatment differences. Post hoc analyses of potentially confounding covariates and alternative methods of imputing missing data did not substantially alter the results. Because of the violations of normality assumptions for the SIB and ADCS-ADL19, nonparametric analyses were performed; statistically significant benefit of memantine over placebo was demonstrated at week 24 for the SIB but not the ADCS-ADL19. The type and incidence of adverse events were similar in both groups.

Memantine in Patients with Moderate to Severe Alzheimer's Disease: Meta-Analyses Using Realistic Definitions of Response

“…Nine relevant studies had accessible data and were included in the post hoc responder analyses (table 1). These included the 6 pivotal phase III memantine studies previously evaluated by the EMA [3,7,8] (MEM-MD-10 [11], LU-99679 [12], MEM-MD-12 [13], MRZ-9605 [14], MEM-MD-01 [15], and MEM-MD-02 [16]) as well as 3 additional studies which have become accessible since then (IE-2101 [17], LU-10116 [18], and MEM-MD-22 [19]). All studies were 24 weeks in duration, except for study MRZ-9605 (28 weeks) and study LU-10116 (16 weeks).…”

Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

“…[214][215][216] It has also been shown to improve behavioural disturbances, such as agitation and aggression. Its mechanism of action as an NMDA receptor antagonist differs from the cholinesterase inhibitors approved for the treatment of Alzheimer disease (i.e., donepezil, galantamine and revastigmine), suggesting a theoretical potential to be used in combination with these drugs.…”

Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease

“…The magnitude of benefit from treatment with memantine is similar to the magnitude observed for AChE-Is. Two of three moderate to severe AD trials with memantine showed statistical significance on their primary outcomes (Reisberg et al 2003b;van Dyck et al 2007), including an add-on trial, in which patients on long-term treatment with donepezil, randomized to receive either placebo or add-on memantine, showed that add-on therapy with memantine produced a statistically significant benefit compared to add-on therapy with placebo (Tariot et al 2004).…”