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Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD. Methods We did a randomised, parallel group, double-blind, placebo-controlled trial of 20 mg memantine taken orally daily for 26 weeks in patients with FTD. Participants met Neary criteria for behavioural variant FTD (bvFTD) or semantic dementia and had characteristic brain atrophy. Use of acetylcholinesterase inhibitors was prohibited. Individuals were randomly assigned to receive either memantine or matched placebo tablets (1:1) in blocks of two and four patients. All patients and study personnel were masked to treatment assignment. Primary endpoints were the change in total NPI score and clinical global impression of change (CGIC) score after 26 weeks and were analysed by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00545974. Findings Of 100 patients screened, 81 were randomly assigned to receive memantine (39 patients) or placebo (42 patients). Five (6%) patients discontinued, and 76 completed the 26-week treatment. Enrolment numbers were lower than planned because of many patients' preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. Memantine treatment had no effect on either the NPI (mean difference 2·2, 95% CI -3·9 to 8·3, p=0·47) or CGIC (mean difference 0·0, -0·4 to 0·4, p=0·90) after 26 weeks of treatment. Memantine was generally well tolerated; however, patients in the memantine group had more frequent cognitive adverse events (six patients) than those in the placebo group (one). Interpretation Memantine treatment showed no benefit in patients with FTD. These data do not support memantine use in FTD. Funding Forest Research Institute.
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“Likewise memantine, an NMDA receptor antagonist, approved for moderate to severe AD, has shown no benefit in patients with bvFTD [38].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [38]
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Metadata
- Authors
- Boxer, A. L., Knopman, D. S., Kaufer, D. I., Grossman, M., Onyike, C., Graf-Radford, N., Mendez, M., Kerwin, D., Lerner, A., Wu, C.-K., Koestler, M., Shapira, J., Sullivan, K., Klepac, K., Lipowski, K., Ullah, J., Fields, S., Kramer, J. H., Merrilees, J., Neuhaus, J., Mesulam, M. M., & Miller, B. L.
- Affiliations
- University of California, San Francisco (US)
- Mayo Clinic (US)
- University of North Carolina at Chapel Hill (US)
- University of Pennsylvania (US)
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- Northwestern University (US)
- Case Western Reserve University (US)
- Texas Tech University (US)
- Corresponding author
- Boxer, Adam L
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 12
- Issue
- 2
- Pages
- 149-156
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC3756890
- OpenAlex
- W2106046611
- Cited by
- 228
- References
- 31
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 7 · 2023: 8 · 2022: 16 · 2021: 17 · 2020: 15 · 2019: 21 · 2018: 15 · 2017: 22 · 2016: 21 · 2015: 23 · 2014: 24 · 2013: 18
- FWCI
- 20.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Larry L. Hillblom Foundation (P50 AG1657303)
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- Agouron Institute
- TauRx Pharmaceuticals
- National Institutes of Health (UL1TR000150)
- Genentech
- University of California, San Francisco (P50 AG023501, P01AG019724)
- National Institute on Aging (P50AG1657303, R01AG031278, P30AG013854, R01AG038791, P01AG019724, P50AG023501)
- National Institute on Deafness and Other Communication Disorders (R01DC008552)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- memantine, frontotemporal lobar degeneration, behavioral variant frontotemporal dementia, semantic dementia, neuropsychiatric symptoms, NPI, Clinical Global Impression of Change, treatment efficacy, drug tolerability
- MeSH terms
- Aged, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Memantine, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Retrospective Studies, Chi-Square Distribution, Treatment Outcome, Excitatory Amino Acid Antagonists, Frontotemporal Lobar Degeneration
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