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. 2020 Nov;10(11):e01831.
doi: 10.1002/brb3.1831. Epub 2020 Sep 10.

Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis

Jiaxun Guo  1 , Zhenyu Wang  1 , Ruishu Liu  2 , Yunxia Huang  1 , Nan Zhang  1 , Ruihan Zhang  1
Affiliations

Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis

Jiaxun Guo et al. Brain Behav. 2020 Nov.

Abstract

Introduction: Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and donepezil are frequently used in its treatment, both as monotherapy and in combination. This multiple treatment comparison meta-analysis assessed the efficacy of these regimens and placebo in the management of AD.

Methods: We searched PubMed, Embase, the Cochrane Library, and Wanfang Med Online and China National Knowledge Infrastructure for English and Chinese publications from the first records to 17 April 2020. Two investigators scanned articles for placebo-controlled trials of memantine and donepezil alone and in combination. We extracted data on the following outcomes: cognition, global assessment, daily activities, neuropsychiatric symptoms, adverse events, and the acceptability and cost of these treatment regimens.

Results: Of 936 records screened, we included 54 trials in this analysis. The combination therapy was more effective in improving cognition (mean difference (MD)-5.01, 95% credible interval (95% Crl) -10.73 to 0.86 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale; MD 9.61, 95% Crl 2.29 to 16.97 in the Severe Impairment Battery), global assessment (MD -2.88, 95% Crl -6.04 to 0.40), daily activities (MD 13.06, 95% Crl -34.04 to 58.92), and neuropsychiatric symptoms (MD -6.84, 95% Crl -10.62 to -2.82) compared with placebo. Memantine was more acceptable than placebo (MD 0.93, 95% Crl 0.69 to 1.22).

Conclusions: Memantine plus donepezil showed superior outcomes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower acceptability than monotherapy and placebo. Combination therapy may be more cost-effective, because memantine slows the progression of AD.

Keywords: Acceptability of healthcare; Activities of daily living; Alzheimer disease; Cognitive function; Cost effectiveness; Disease progress.

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Conflict of interest statement

The authors declare that there have no conflicts of interest.

Figures

Figure 1
Figure 1
Study selection for a network meta‐analysis on Alzheimer's disease treatment (flow diagram)
Figure 2
Figure 2
Risk of bias in studies selected for a network meta‐analysis on Alzheimer's disease treatment. Summary based on Review Manager, version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) assessment
Figure 3
Figure 3
(a) Network meta‐analysis on Alzheimer's disease treatment. Cognition assessment using the Assessment Scale‐cognition subscale. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine; ADAS‐cog, Assessment Scale‐cognition subscale; MD, mean difference; Crl, credible interval. (b) Network meta‐analysis on Alzheimer's disease treatment. Cognition assessment using the Severe Impairment Battery. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine; SIB, Severe Impairment Battery; MD, standardized mean difference; Crl, credible interval
Figure 4
Figure 4
Network meta‐analysis on Alzheimer's disease treatment. Assessment of the change in the clinical global impression. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine; CGI, clinical global impression; MD, standardized mean difference; Crl, credible interval
Figure 5
Figure 5
Network meta‐analysis on Alzheimer's disease treatment. Assessment of Alzheimer's Disease Cooperative Study‐Activities of Daily Living and Activities of Daily Living. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine; ADCS‐ADL, Alzheimer's Disease Cooperative Study‐Activities of Daily Living; ADL, Activities of Daily Living; MD, standardized mean difference; Crl, credible interval
Figure 6
Figure 6
Network meta‐analysis on Alzheimer's disease treatment. Assessment of Neuropsychiatric Inventory. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine; NPI, Neuropsychiatric Inventory; MD, standardized mean difference; Crl, credible interval
Figure 7
Figure 7
Network meta‐analysis on Alzheimer's disease treatment. Analysis of acceptability. Don, donepezil; mem, memantine; mem + don, combination of donepezil and memantine. MD, standardized mean difference; Crl, credible interval
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