Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer’s disease: post-hoc analysis of a randomized placebo-controlled study

Abstract

BackgroundA large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer’s disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome.MethodsRandomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints.ResultsOverall, 496 (24.3 %) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p = 0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p < 0.0001) and DAD scores (58.0 (23.49) vs 62.5 (20.52), p < 0.0001) than nonusers. Mortality rates (per 100 patient-years) in memantine nonusers (n = 1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24 months, the decline in MMSE scores (effect size (95 % CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores.ConclusionThis post-hoc analysis shows that the beneficial effects of galantamine at 2 years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation.Trial registrationClinicalTrials.gov NCT00679627. Registered 15 May 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0214-x) contains supplementary material, which is available to authorized users.

Proportion of Women and Reporting of Outcomes by Sex in Clinical Trials for Alzheimer Disease

“…To assess whether subsequent articles for a given RCT reported sex-stratified data, we also considered the secondary articles. We found that in this group of 13 articles, [89][90][91][92][93][94][95][96][97][98][99][100][101] a sex-specific data analysis was present in 4 (30.8%). 91,92,99,100 Using a pooled data set from primary and secondary articles (Figure 3 and eFigure 2 in the Supplement), we found a statistically significant increasing temporal trend of articles that referenced a sex-specific data analysis in the methods (R, 0.30; 95% CI, 0.05-0.59; P = .03) and a similar trend for sex stratification in the results (R, 0.26; 95% CI, 0.01-0.55; P = .055).…”

Dificuldades Enfrentadas Pelos Profissionais De Saúde Frente Às Emergências Psiquiátricas

“…A combinação da memantina com inibidores da acetilcolinesterase pode ser utilizada no tratamento da AD devido aos dois mecanismos de ação atuarem de forma a melhorar o processo cognitivo do doente. (HAGER et al, 2016) O canabidiol (CBD) é uma substância da planta Cannabis sativa, não tem efeito psicotrópico e sua molécula atravessa livremente a barreira hematoencefálica, que é uma estrutura especial que envolve os vasos sanguíneos do sistema nervoso central e tem uma função metabólica importante, protegendo-o de substâncias potencialmente tóxicas.…”

The Development of Pharmacological Therapies for Alzheimer’s Disease

“…A 2-year randomized study showed a clinical benefit of galantamine in mild-to-moderate dementia patients in terms of reducing cognitive or functional decline, mortality and nursing home placement [ 76 ]. Surprisingly, a post hoc analysis of the same study revealed that such benefits were diminished in patients additionally taking memantine [ 77 ].…”