Dataset Information

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

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.

SUBMITTER: Dou KX

PROVIDER: S-EPMC6309083 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Dou Kai-Xin KX Tan Meng-Shan MS Tan Chen-Chen CC Cao Xi-Peng XP Hou Xiao-He XH Guo Qi-Hao QH Tan Lan L Mok Vincent V Yu Jin-Tai JT

Alzheimer's research & therapy 20181227 1

<h4>Background</h4>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.<h4>Methods</h4>We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 20 ...[more]

PMID: 30591071

Similar Datasets

Project description:BackgroundPharmacological treatment of Alzheimer's disease (AD) involves symptomatic improvement of cognition using cholinesterase inhibitors (ChEIs) and memantine. The cost-effectiveness of these medications will guide decision-makers in making judicious use of scarce healthcare resources, particularly during the advanced disease stages.ObjectiveTo evaluate the cost-effectiveness of ChEIs, memantine, and ChEI-memantine combinations in persons with moderate-to-severe AD from the US healthcare perspective.MethodsThis pharmacoeconomic evaluation study used a state-transition Markov cohort model to simulate the costs and effectiveness of ChEI-memantine combinations compared with monotherapies of ChEI (donepezil, galantamine and rivastigmine) and memantine in persons with moderate-to-severe AD over a lifetime horizon with a 1-year cycle length. We estimated expected quality-adjusted life-years (QALYs), costs (in 2020 $US), net monetary benefits, and incremental cost-effectiveness ratios (ICERs). We discounted future costs and QALYs at the rate of 3%.ResultsIn this study, donepezil monotherapy, galantamine-memantine combination, and rivastigmine transdermal patch formed the cost-effectiveness frontier. Findings suggests that rivastigmine transdermal patch is the optimal treatment strategy at a willingness-to-pay (WTP) threshold of $150,000/QALY (ICER = $93,307/QALY [versus donepezil monotherapy]). Results across subgroups by age and sex also suggest that the rivastigmine transdermal patch is the optimal treatment strategy with the highest net benefit.ConclusionFrom the US healthcare perspective, we found that, for persons with moderate-to-severe AD at a WTP threshold of $150,000/QALY, the rivastigmine transdermal patch is the most cost-effective pharmacological treatment option. Given that the transdermal patch is a preferred route of administration for persons with AD and their caregivers due to its convenience, our findings provide additional incentives for its use.

Project description:IntroductionImmediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors.MethodsIn this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations.ResultsA total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %).ConclusionExtended-release memantine was efficacious, safe, and well tolerated in this population.

Project description:IntroductionAlzheimer's disease (AD) is the most common neurodegenerative form of dementia. Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs) and memantine, have been available in the USA since 2000. Over the past decade, few studies have analyzed real-world anti-dementia treatment patterns in the USA. This study evaluated monotherapy AChEIs and memantine treatment patterns among newly diagnosed AD patients.MethodsA retrospective cohort study was conducted using Medicare data and the Minimum Data Set from 2008 to 2012. Patients aged 65-100 years with newly diagnosed AD (ICD-9 code: 331.0) and monotherapy AChEI or memantine treatment initiated after diagnosis were included. Descriptive treatment pattern analyses, including discontinuation and switch, were undertaken. Kaplan-Meier curves were developed to examine the treatment duration.ResultsA total of 9812 newly diagnosed AD patients were identified, with 56.7% (n = 5567) first receiving anti-dementia treatment after the initial AD diagnosis. Among patients initiating monotherapy AChEIs or memantine after AD diagnosis (N = 5200), 51.6% continued index treatment during the entire follow-up period (mean follow-up: 659.7 days) and 21.7% discontinued treatment. Of those who initiated monotherapy treatment with an AChEI, 11.1% received adjunct therapy with memantine. Among patients with ≥1 year of continuous treatment (mean follow-up: 834 days), 75.6% remained on the index drug, 10.2% discontinued during the remaining follow-up period, and 9.5% of the AD patients initiating AChEIs received adjunct memantine therapy during the remaining follow-up period.ConclusionIn the USA Medicare population, about 50% of the patients who initiated treatment with AChEI or memantine after diagnosis continued the index treatment, and more than 20% discontinued and were untreated afterwards over the observation period. AD patients initiating AChEIs or memantine were more likely to remain on their treatment if they were persistently treated for the first year.

Project description:Memantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer.To compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results.Systematic review and meta-analysis of randomised controlled trials.The Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011.Data from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine.Pooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=-0.29, 95% CI -0.45 to -0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=-0.20, 95% CI -0.31 to -0.09), cognition (SMD=-0.25, 95% CI -0.36 to -0.14) and behaviour and mood (SMD=-0.17, 95% CI -0.32 to -0.03) but not on function (SMD=-0.04, 95% CI -0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found 'no significant benefit' on any clinical measures at 1 year.These results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe.

Project description:Importance:Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. Objective:To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. Data Sources:Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. Study Selection:All studies with data on ChEI and memantine use that included assessment of specified outcome measures. Data Extraction and Synthesis:The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. Main Outcomes and Measures:Annual rate of change on the ADAS-cog. Results:Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). Conclusions and Relevance:Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.

Project description:Background:Dementia is a large and growing health care burden globally, and its major cause is Alzheimer's disease (AD). MLC901 (Neuroaid II) is a simplified form of MLC601 (Neuroaid), a Traditional Chinese Medicine with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury. MLC601 has been shown to modulate amyloid precursor protein (APP) processing in human neuroblastoma cell cultures and increase the levels of soluble APP?. In addition, MLC901 has been shown to reduce tau phosphorylation in vitro. Hence, MLC901 may have possible multimodal actions and a disease-modifying effect in AD. In previous clinical studies, MLC601 has shown promising effects in AD. Objective:To investigate the safety and efficacy of MLC901 add-on therapy to standard treatment in mild-to-moderate probable AD patients stable on standard treatment and to evaluate if MLC901 has a disease-modifying effect in AD. Methods:This is a 6-month randomized, double-blind, placebo-controlled trial in mild-to-moderate probable AD where MLC901 will be given as an add-on therapy to standard AD treatment, followed by an extension study for another 6 months, where all subjects will be treated with open-label MLC901 in addition to standard treatment. The primary outcome is safety as measured by adverse events, vital signs, electrocardiogram, laboratory tests, and physical and neurological examinations. Secondary outcomes evaluating cognition, behavior, and activities of daily living at various time points include the Alzheimer's Disease Assessment Scale-cognitive subscale, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Mini-Mental State Examination. Conclusion:MLC901 has the potential to improve cognition in AD patients. It may also have a role in delaying disease progression. This study will be the first to provide safety and efficacy data for MLC901 in mild-to-moderate probable AD patients already receiving standard therapy.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets