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. 2018 Dec 27;10(1):126.
doi: 10.1186/s13195-018-0457-9.

Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer's disease: a network meta-analysis of 41 randomized controlled trials

Kai-Xin Dou  1 , Meng-Shan Tan  1 , Chen-Chen Tan  1 , Xi-Peng Cao  2 , Xiao-He Hou  1 , Qi-Hao Guo  3 , Lan Tan  4 , Vincent Mok  5   6   7 , Jin-Tai Yu  8   9
Affiliations

Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer's disease: a network meta-analysis of 41 randomized controlled trials

Kai-Xin Dou et al. Alzheimers Res Ther. .

Abstract

Background: Cholinesterase inhibitors and memantine have been approved for management of Alzheimer's disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs.

Methods: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis.

Results: Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference - 0.51, 95% credible interval - 0.67 to - 0.35), galantamine 24 mg daily (- 0.50, - 0.61 to - 0.40), and donepezil 10 mg daily (- 0.40, - 0.51 to - 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm2 patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis.

Conclusions: Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms.

Keywords: Alzheimer’s disease; Cholinesterase inhibitors; Memantine; Network meta-analysis.

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Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Flow diagram of study selection
Fig. 2
Fig. 2
Network of eligible comparisons of cognition for mild to moderate AD (a) and moderate to severe AD (b). Width of lines proportional to number of trials comparing every pair of treatments, and size of every node proportional to number of randomly assigned participants (sample size). DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmine
Fig. 3
Fig. 3
Comparative efficacy and tolerability for mild to moderate AD in the network meta-analysis: comparisons should be read from left to right. Efficacy and tolerability estimate located at intersection of column-defining treatment and row-defining treatment. For efficacy (mean changes of cognition), SMD < 0 favors column-defining treatment. For tolerability (all-cause adverse events), OR < 1 favors row-defining treatment. Significant results bold and underlined. CrI credible interval, DON donepezil, GAL galantamine, MEM memantine, OR odds ratio, PBO placebo, RIV rivastigmine, SMD standardized mean difference
Fig. 4
Fig. 4
Rank for efficacy on cognition (solid line) and tolerability (dotted line) for mild to moderate AD. Ranking (x axis) indicates probability to be best treatment, second best, third best, and so on. DON donepezil, GAL galantamine, MEM memantine, PBO placebo, RIV rivastigmine
Fig. 5
Fig. 5
Forest plots of network meta-analysis of efficacy on function (a) and global changes (b) compared with placebo. SMD standardized mean difference, OR odds ratio, CrI credible interval
See this image and copyright information in PMC

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