Tolerability and efficacy of memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer's disease: a multicenter, randomized, open-label, parallel-group study

Choi, Seong Hye; Park, Kyung Won; Na, Duk L.; Han, Hyun Jeong; Kim, Eun-Joo; Shim, Yong S.; Lee, Jae Hong

doi:10.1185/03007995.2011.582484

Cited by 57 publications

(53 citation statements)

References 28 publications

(30 reference statements)

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“…The effect of concomitant memantine use on the efficacy, safety and tolerability of 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate AD has been previously investigated [24,25]. An open-label study reported no marked differences in the safety or efficacy of combination therapy with 9.5 mg/24 h rivastigmine patch and memantine compared with 9.5 mg/24 h rivastigmine patch alone in patients with mild-to-moderate AD [24].…”

Section: Discussionmentioning

confidence: 99%

“…An open-label study reported no marked differences in the safety or efficacy of combination therapy with 9.5 mg/24 h rivastigmine patch and memantine compared with 9.5 mg/24 h rivastigmine patch alone in patients with mild-to-moderate AD [24]. Furthermore, post-hoc analysis of a 25-week, randomized, open-label study reported a non-significant increase in the incidence of AEs in patients with mild-to-moderate AD treated with 9.5 mg/24 h rivastigmine patch plus memantine, compared with memantine alone (73.3% versus 67.5%) [25].…”

Section: Discussionmentioning

confidence: 99%

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Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

Grossberg

Farlow²,

Meng³

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

Grossberg

Farlow²,

Meng³

et al. 2015

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“…This study is based on the EXelon Patch and combination with the mEmantine Comparative Trial (EXPECT) study, which was a randomized, multicenter, parallel group, open-label trial of the rivastigmine transdermal patch or memantine add-on treatment in probable AD patients [11,12]. The study duration was 24 weeks and included a 16-week randomized study with an 8-week run-in period.…”

Section: Methodsmentioning

confidence: 99%

Effect of Rivastigmine or Memantine Add-on Therapy Is Affected by Butyrylcholinesterase Genotype in Patients with Probable Alzheimer's Disease

et al. 2014

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Background: The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene. Objective: To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene. Methods: A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score. Results:BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E I 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables. Conclusion: The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E I 4. i 2014 S. Karger AG, Basel

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“…Several clinical studies demonstrate that combined treatment with memantine and ChEI is safe and well-tolerated [58]. Indeed, efficacies of both drugs in AD patients have already been investigated.…”

Section: Discussionmentioning

confidence: 99%

Combined Memantine and Donepezil Treatment Improves Behavioral and Psychological Symptoms of Dementia-Like Behaviors in Olfactory Bulbectomized Mice

et al. 2017

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Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed. Here, we investigate combined memantine/donepezil effects on cognitive impairment and BPSD-like behaviors in olfactory bulbectomized (OBX) mice. Interestingly, combined administration synergistically improved both depressive-like behaviors and impaired social interaction in OBX mice, whereas only weak synergistic effects on cognitive performance were seen. To address mechanisms underlying these effects, we used in vivo microdialysis study and observed impaired nicotine-induced serotonin (5-HT) release in OBX mouse hippocampus. Combined memantine/donepezil administration, but not single administration of either, significantly antagonized the decrease in nicotine-induced 5-HT release seen in OBX mouse hippocampus. Furthermore, decreased autophosphorylation of calcium/calmodulin dependent protein kinase II (CaMKII) was rescued in hippocampal CA1 and dentate gyrus of OBX mice by combined memantine/donepezil administration. These results suggest that improvement of BPSD-like behaviors by the co-administration of both drugs is in part mediated by enhanced 5-HT release and CaMKII activity in OBX mouse hippocampus.

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Tolerability and efficacy of memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer's disease: a multicenter, randomized, open-label, parallel-group study

Cited by 57 publications

References 28 publications

Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

Effect of Rivastigmine or Memantine Add-on Therapy Is Affected by Butyrylcholinesterase Genotype in Patients with Probable Alzheimer's Disease

Combined Memantine and Donepezil Treatment Improves Behavioral and Psychological Symptoms of Dementia-Like Behaviors in Olfactory Bulbectomized Mice

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