Abstract
BackgroundThe risk-benefit relationship of memantine treatment for Alzheimer’s disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates.MethodsA systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials.ResultsEighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE.ConclusionsOur study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship.PROSPERO registrationCRD42014015696.
Highlights
The risk-benefit relationship of memantine treatment for Alzheimer’s disease (AD) remains unclear
It is approved for the treatment of moderate to severe AD [6, 7], and some guidelines support using it in combination with a cholinesterase inhibitor (ChEI) [8] whereas others do not recommend it because important gaps in the evidence exist [9]
We considered that memantine was administered in combination with ChEI when more than 50% of patients received donepezil, galantamine or rivastigmine
Summary
The risk-benefit relationship of memantine treatment for Alzheimer’s disease (AD) remains unclear. Memantine has been associated with several side effects such as dizziness, headaches, constipation, somnolence, hypertension and agitation, some of which may be serious [6, 7, 13] In this context, it is difficult to weigh memantine’s efficacy against its safety. It is difficult to weigh memantine’s efficacy against its safety This problem can be partly overcome using “all-cause treatment discontinuation”, a pragmatic outcome that reflects therapeutic benefits in relation to undesirable effects [15]. It is unaffected by attrition bias as this outcome has no missing data. Treatment discontinuation has been used previously in the field of AD [15,16,17] and other disorders [18,19,20]
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