Trial reportCNS drugs2013
The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors.
Trial report in CNS drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00322153 (A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Memantine in Patients With Moderate-to-Severe Dementia of the Alzheimer's Type), which is not on this map. Cited by 67 papers, 11 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Memantine in Patients With Moderate-to-Severe Dementia of the Alzheimer's Type
Who cites it
67 citing papers in PubMed, 11 syntheses or guidelines pooled it, 155 citations in OpenAlex.
- Comparative efficacy and safety of symptomatic therapy and disease-modifying therapy for Alzheimer's disease: a systematic review and network meta-analysis.Frontiers in neuroscience · 2025Pooled it
- Efficacy of 5 and 10 mg donepezil in improving cognitive function in patients with dementia: a systematic review and meta-analysis.Frontiers in neuroscience · 2024Pooled it
- Alzheimer's Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review.Journal of geriatric psychiatry and neurology · 2022Pooled it
- Palliative care interventions in advanced dementia.The Cochrane database of systematic reviews · 2021Pooled it
- Proportion of Women and Reporting of Outcomes by Sex in Clinical Trials for Alzheimer Disease: A Systematic Review and Meta-analysis.JAMA network open · 2021Pooled it
- Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia.The Cochrane database of systematic reviews · 2021Pooled it
- Memantine for dementia.The Cochrane database of systematic reviews · 2019Pooled it
- Pooled it
- Palliative care interventions in advanced dementia.The Cochrane database of systematic reviews · 2016Pooled it
- Efficacy and adverse effects of memantine treatment for Alzheimer's disease from randomized controlled trials.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2015Pooled it
- Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis.The international journal of neuropsychopharmacology · 2014Pooled it
- Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise.Metabolic brain disease · 2021Trial
- A novel once-daily fixed-dose combination of memantine extended release and donepezil for the treatment of moderate to severe Alzheimer's disease: two phase I studies in healthy volunteers.Clinical drug investigation · 2015Trial
- Effect of memantine on cough reflex sensitivity: translational studies in guinea pigs and humans.The Journal of pharmacology and experimental therapeutics · 2015Trial
- Memantine ER Maintains Patient Response in Moderate to Severe Alzheimer's Disease: Post Hoc Analyses From a Randomized, Controlled, Clinical Trial of Patients Treated With Cholinesterase Inhibitors.Alzheimer disease and associated disordersTrial
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- The impact of recent approvals on future alzheimer's disease clinical development: Statistical considerations for combination trials.The journal of prevention of Alzheimer's disease · 2025Article
- Impact of Gut-Brain Axis and Probiotics on Alzheimer's Disease.Neurology international · 2025Review
- Neuroprotective Effects of Tectoridin in HNeurochemical research · 2025Article
- Exploring the Mechanisms and Therapeutic Approaches of Mitochondrial Dysfunction in Alzheimer's Disease: An Educational Literature Review.Molecular neurobiology · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.