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Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, Memantine Study Group.. JAMA, 2004-01-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Context Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed. Objective To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil. Design, setting, and participants A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial. Interventions Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n = 203) or placebo (n = 201) for 24 weeks. Main outcome measures Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale). Results The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P Conclusions In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.
What this study adds
Evidence grade: High
This is a trial of 203 participants. In this 24-week trial of 404 people with moderate to severe Alzheimer's who were already on stable donepezil, those given memantine as well kept their cognition scores steady (+0.9 on a 0–100 scale), while those given placebo declined (−2.5). The authors report that adding memantine "resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated".
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., Gergel, I., et al. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. https://doi.org/10.1001/jama.291.3.317
Vancouver
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004. doi:10.1001/jama.291.3.317. PMID: 14734594.
BibTeX
@article{tariot2004-14734594,
author = {Tariot, P. N. and Farlow, M. R. and Grossberg, G. T. and Graham, S. M. and McDonald, S. and Gergel, I. and {Memantine Study Group}},
title = {{Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial}},
journal = {JAMA},
year = {2004},
doi = {10.1001/jama.291.3.317},
pmid = {14734594},
url = {https://doi.org/10.1001/jama.291.3.317}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.
- Results The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03).
- These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.
Why it matters
In this 24-week trial of 404 people with moderate to severe Alzheimer's who were already on stable donepezil, those given memantine as well kept their cognition scores steady (+0.9 on a 0–100 scale), while those given placebo declined (−2.5). The authors report that adding memantine "resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated". However, only the cognition figures survive in this record. The trial covers only people already taking donepezil and only six months of treatment, so it supports memantine as an add-on in that group. It does not show that memantine slows the disease.
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Study details
- Participants203
- Evidence strengthHigh
How this study scored 81/100
Published in a top-tier journal, and it is a randomized controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 78 of the 96 points we could judge it on, which is 81 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — older than 20 years, still counted |
| Sample size | 2 / 4 | 203 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 7 / 7 | Cited 1,404 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 58.5 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 6 / 6 | Cited 75.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 40 other studies in this library |
| Still being cited | 3 / 4 | Cited 108 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author for the Memantine Study Group holds only 1 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | University of Rochester Medicine: institution h-index 953 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14734594) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 78 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 78 of the 96 points we could judge it on is 81 out of 100. |
| Total | 81 / 100 | — |
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