Memantine therapy of behavioral symptoms in community-dwelling patients with moderate to severe Alzheimer's disease
Abstract
Memantine is a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate receptors, approved for the treatment of moderate to severe Alzheimer's disease (AD). Available data suggest that, in addition to its benefits on cognition, function, and global status, memantine treatment may also help alleviate behavioral symptoms. This article provides an overview of the prevalence, assessment, and treatment of behavioral disturbances in AD, and summarizes current knowledge regarding the effects of memantine on the behavior of community-dwelling patients. We searched EMBASE and PubMed (January 1992 to October 2008) for reports on memantine trials that involved outpatients with moderate to severe AD. All previously unpublished data were obtained from Forest Laboratories, Inc. Behavioral outcomes were assessed in three completed, double-blind, placebo-controlled trials.Overall, patients who received memantine performed better on behavioral measures than those treated with placebo. Post-hoc analyses suggest that memantine treatment was associated with a reduced severity or emergence of specific symptoms, particularly agitation and aggression. Prospective, well-designed trials are warranted to evaluate the efficacy of memantine in patients with significant behavioral symptoms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In moderate and severe AD, short-term efficacy of memantine monotherapy compared with placebo is reported in several randomized controlled trials of 12 to 50 weeks duration and supported by meta-analyses.
“In moderate and severe AD, short-term efficacy of memantine monotherapy compared with placebo is reported in several RCTs of 12 to 50 weeks duration and supported by meta-analyses.”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [103]
Cites
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia
Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051688 · Cited by 5,892 · see citing works
The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration
Altman, D. G., Schulz, K. F., Moher, D., Egger, M., Davidoff, F., Elbourne, D., Gøtzsche, P. C., Lang, T., & for the CONSORT Group (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-8-200104170-00012 · Cited by 3,835 · see citing works
Lyketsos, C. G., Lopez, O., Jones, B., Fitzpatrick, A. L., Breitner, J., & DeKosky, S. (2002) · JAMA · doi:10.1001/jama.288.12.1475 · Cited by 2,049 · see citing works
Memantine in Moderate-to-Severe Alzheimer's Disease
Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S., & Möbius, H. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa013128 · Cited by 2,043 · see citing works
Moher, D., Schulz, K. F., Altman, D. G., & for the CONSORT Group* (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-8-200104170-00011 · Cited by 1,426 · see citing works
Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., Gergel, I., & for the Memantine Study Group (2004) · JAMA · doi:10.1001/jama.291.3.317 · Cited by 1,403 · see citing works
Self-citationEffectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease
Schneider, L. S., Tariot, P. N., Dagerman, K. S., Davis, S. M., Hsiao, J. K., Ismail, M. S., Lebowitz, B. D., Lyketsos, C. G., Ryan, J. M., Stroup, T. S., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061240 · Cited by 1,206 · see citing works
McShane, R., Areosa Sastre, A., & Minakaran, N. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003154.pub5 · Cited by 1,155 · see citing works
The spectrum of behavioral changes in Alzheimer's disease
Mega, M., Cummings, J., Fiorello, T., & Gornbein, J. (1996) · Neurology · doi:10.1212/wnl.46.1.130 · Cited by 1,124 · see citing works
Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder
(2008) · APA Practice Guidelines for the Treatment of Psychiatric Disorders: Comprehensive Guidelines and Guideline Watches · doi:10.1176/appi.books.9780890423363.149114 · Cited by 1,028 · see citing works
Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia: A Review of the Evidence
Sink, K. M., Holden, K. F., & Yaffe, K. (2005) · JAMA · doi:10.1001/jama.293.5.596 · Cited by 910 · see citing works
Patient and Caregiver Characteristics and Nursing Home Placement in Patients With Dementia
Yaffe, K. (2002) · JAMA · doi:10.1001/jama.287.16.2090 · Cited by 903 · see citing works
Parsons, C. G., Stöffler, A., & Danysz, W. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.07.013 · Cited by 701 · see citing works
Antipsychotic Drug Use and Mortality in Older Adults with Dementia
Gill, S. S., Bronskill, S. E., Normand, S.-L. T., Anderson, G. M., Sykora, K., Lam, K., Bell, C. M., Lee, P. E., Fischer, H. D., Herrmann, N., et al. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-11-200706050-00006 · Cited by 624 · see citing works
Atypical antipsychotics for aggression and psychosis in Alzheimer's disease
Ballard, C. G., Waite, J., & Birks, J. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003476.pub2 · Cited by 528 · see citing works
Psychosis of Alzheimer's Disease and Related Dementias: Diagnostic Criteria for a Distinct Syndrome
Jeste, D. V., & Finkel, S. I. (2000) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200002000-00004 · Cited by 394 · see citing works
Neuropsychiatric Syndromes in Dementia
Aalten, P., Verhey, F. R. J., Boziki, M. K., Bullock, R. A., Byrne, E. J., Camus, V., Caputo, M., Collins, D., Deyn, P. P. D., Elina, K., et al. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000110738 · Cited by 388 · see citing works
Schneeweiss, S., Setoguchi, S., Brookhart, A., Dormuth, C., & Wang, P. S. (2007) · Canadian Medical Association Journal · doi:10.1503/cmaj.061250 · Cited by 366 · see citing works
Delusions and Hallucinations Are Associated With Worse Outcome in Alzheimer Disease
Scarmeas, N., Brandt, J., Albert, M., Hadjigeorgiou, G. M., Papadimitriou, A., Dubois, B., Sarazin, M., Devanand, D. P., Honig, L. S., Marder, K. S., et al. (2005) · Archives of Neurology · doi:10.1001/archneur.62.10.1601 · Cited by 350 · see citing works
The Evolution of Psychiatric Symptoms in Alzheimer's Disease: A Natural History Study
Jost, B. C., & Grossberg, G. T. (1996) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1996.tb02942.x · Cited by 341 · see citing works
Self-citationDonepezil for the Treatment of Agitation in Alzheimer's Disease
Howard, R. J., Juszczak, E., Ballard, C. G., Bentham, P., Brown, R. G., Bullock, R., Burns, A. S., Holmes, C., Jacoby, R., Johnson, T., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066583 · Cited by 327 · see citing works
Provisional Diagnostic Criteria for Depression of Alzheimer Disease: Rationale and Background
Olin, J. T., Katz, I. R., Meyers, B. S., Schneider, L. S. S., & Lebowitz, B. D. (2002) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200203000-00004 · Cited by 315 · see citing works
Memantine Treatment in Mild to Moderate Alzheimer Disease: A 24-Week Randomized, Controlled Trial
Peskind, E. R., Potkin, S. G., Pomara, N., Ott, B. R., Graham, S. M., Olin, J. T., & McDonald, S. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000224350.82719.83 · Cited by 306 · see citing works
Self-citationMusic therapy in moderate and severe dementia of Alzheimer's type: a case-control study
Svansdottir, H. B., & Snaedal, J. (2006) · International Psychogeriatrics · doi:10.1017/s1041610206003206 · Cited by 288 · see citing works
Psychiatric Symptoms Vary With the Severity of Dementia in Probable Alzheimer's Disease
Lopez, O. L., Becker, J. T., Sweet, R. A., Klunk, W., Kaufer, D. I., Saxton, J., Habeych, M., & DeKosky, S. T. (2003) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.15.3.346 · Cited by 286 · see citing works
Schnaider Beeri, M., Werner, P., Davidson, M., & Noy, S. (2002) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.490 · Cited by 284 · see citing works
Porsteinsson, A., Grossberg, G., Mintzer, J., & Olin, J. (2008) · Current Alzheimer Research · doi:10.2174/156720508783884576 · Cited by 272 · cited 1× · see citing works
“were combined with those of patients from the three memantine trials in mild to moderate AD [”
ResultSelf-citationThe incremental direct costs associated with behavioral symptoms in AD
Murman, D. L., Chen, Q., Powell, M. C., Kuo, S. B., Bradley, C. J., & Colenda, C. C. (2002) · Neurology · doi:10.1212/01.wnl.0000036904.73393.e4 · Cited by 258 · see citing works
Memantine in Moderate to Severe Alzheimer’s Disease: a Meta-Analysis of Randomised Clinical Trials
Winblad, B. G., Jones, R. W., Wirth, Y., Stöffler, A., & Möbius, H. J. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000102568 · Cited by 253 · see citing works
Wilcock, G. K., Ballard, C. G., Cooper, J. A., & Loft, H. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0302 · Cited by 253 · see citing works
Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment
Cummings, J. L., Schneider, E., Tariot, P. N., & Graham, S. M. (2006) · Neurology · doi:10.1212/01.wnl.0000223333.42368.f1 · Cited by 223 · see citing works
Self-citationGauthier, S., Loft, H., & Cummings, J. (2008) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1949 · Cited by 220 · see citing works
Gauthier, S. G., Wirth, Y., & Möbius, H. J. (2005) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1341 · Cited by 206 · see citing works
van Dyck, C. H., Tariot, P. N., Meyers, B. S., & Resnick, E. M. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318065c495 · Cited by 181 · see citing works
Guidelines for managing Alzheimer's disease: Part II. Treatment.
Cummings, J. L., Frank, J. C., Cherry, D., Kohatsu, N. D., Kemp, B. J., Hewett, L., & Mittman, B. S. (2002) · PubMed · Cited by 176 · see citing works
Verkaik, R., van Weert, J. C. M., & Francke, A. L. (2005) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1279 · Cited by 175 · see citing works
Caregiver Characteristics Are Associated with Neuropsychiatric Symptoms of Dementia
Sink, K. M., Covinsky, K. E., Barnes, D. E., Newcomer, R. J., & Yaffe, K. S. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00697.x · Cited by 167 · see citing works
Natural history of behavioural changes and psychiatric symptoms in Alzheimer's disease
Hope, T., Keene, J., Fairburn, C. G., Jacoby, R. J., & McShane, R. H. (1999) · The British Journal of Psychiatry · doi:10.1192/bjp.174.1.39 · Cited by 155 · see citing works
Ethnic Differences in the Prevalence and Pattern of Dementia‐Related Behaviors
Sink, K. M., Covinsky, K. E., Newcomer, R. J., & Yaffe, K. S. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52356.x · Cited by 140 · see citing works
Bakchine, S., & Loft, H. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11409 · Cited by 136 · see citing works
Finkel, S. I. (2001) · PubMed · Cited by 118 · see citing works
Cholinesterase Inhibitor Therapies and Neuropsychiatric Manifestations of Alzheimer’s Disease
Wynn, Z. J., & Cummings, J. L. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000074281 · Cited by 116 · see citing works
Pitkälä, K. H., Laurila, J., Strandberg, T. E., & Tilvis, R. S. (2004) · International Psychogeriatrics · doi:10.1017/s1041610204000079 · Cited by 112 · see citing works
Carson, S., McDonagh, M. S., & Peterson, K. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.00566.x · Cited by 103 · see citing works
Meta‐analysis of six‐month memantine trials in Alzheimer's disease
Doody, R. S., Tariot, P. N., Pfeiffer, E. A., Olin, J. T., & Graham, S. M. (2007) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.10.004 · Cited by 102 · see citing works
Self-citationHarwood, D. G., Barker, W., Ownby, R. L., & Duara, R. (2000) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(200005)15:5 · Cited by 102 · see citing works
Mintzer, J., Greenspan, A., Caers, I., Van Hove, I., Kushner, S., Weiner, M., Gharabawi, G., & Schneider, L. S. (2006) · The American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000194643.63245.8c · Cited by 94 · see citing works
The Use of Atypical Antipsychotics in Nursing Homes
Liperoti, R., Mor, V., Lapane, K. L., Pedone, C., Gambassi, G., & Bernabei, R. (2003) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v64n0918 · Cited by 90 · see citing works
Jeste, D. V., Meeks, T. W., Kim, D. S., & Zubenko, G. S. (2006) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988706291087 · Cited by 59 · see citing works
Yohannes, A. M., Baldwin, R. C., & Connolly, M. J. (2000) · International Journal of Geriatric Psychiatry · doi:10.1002/1099-1166(200012)15:12 · Cited by 58 · see citing works
The ABC of Alzheimer's Disease: Behavioral Symptoms and Their Treatment
Grossberg, G. T. (2002) · International Psychogeriatrics · doi:10.1017/s1041610203008652 · Cited by 57 · see citing works
Self-citationBullock, R. A. (2004) · Current Medical Research and Opinion · doi:10.1185/030079904x16777 · Cited by 56 · see citing works
A Regulatory Perspective on Psychiatric Syndromes in Alzheimer Disease
LAUGHREN, T. P. (2001) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200111000-00003 · Cited by 45 · see citing works
The Stockton Geriatric Rating Scale: A Shortened Version with British Normative Data
Gilleard, C. J., & Pattie, A. H. (1977) · The British Journal of Psychiatry · doi:10.1192/bjp.131.1.90 · Cited by 40 · see citing works
Clinical application of operationalized criteria for ‘Depression of Alzheimer's Disease’
Rosenberg, P. B., Onyike, C. U., Katz, I. R., Porsteinsson, A. P., Mintzer, J. E., Schneider, L. S. S., Rabins, P. V., Meinert, C. L., Martin, B. K., & Lyketsos, C. G. (2005) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1261 · Cited by 37 · see citing works
Miller, T. P., Tinklenberg, J. R., Brooks, J. O., et al. (1993) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879300600410 · Cited by 37 · see citing works
Sultzer, D. L. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000074279 · Cited by 31 · see citing works
Psychosis in Elderly Patients: Classification and Pharmacotherapy
Mintzer, J. E., & Targum, S. D. (2003) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988703258658 · Cited by 30 · see citing works
Aarsland, D., Sharp, S. I., & Ballard, C. G. (2005) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-005-0058-4 · Cited by 29 · see citing works
Moretti, R., Torre, P., Antonello, R. M., & Pizzolato, G. (2006) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.6.5.705 · Cited by 19 · see citing works
Pharmacotherapy for behavioral and psychological symptoms of dementia in the elderly
Beier, M. T. (2007) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp060594 · Cited by 17 · see citing works
Guidelines for Managing Alzheimer's Disease
Cummings, J. L., Frank, J. C., Cherry, D., et al. (2002) · Cited by 15 · see citing works
Grossberg, G. T., Manes, F. F., Allegri, R., Gutiérrez‐Robledo, L. M., Gloger, S., Xie, L., Jia, X. D., Perhach, J. L., & Graham, S. M. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.2476 · Cited by 10 · see citing works
Self-citationBEHAVIORAL DISTURBANCES IN ALZHEIMER’S DISEASE: A NON-PHARMACOLOGICAL THERAPEUTIC APPROACH
Silvestri, A., Rosano, G. M. C., Zannino, G. D., Ricca, F., Marigliano, V., & Fini, M. (2004) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2004.04.048 · Cited by 9 · see citing works
Alzheimer's Disease: Pharmacological Treatment and Management
Rivas-Vazquez, R. A., Carrazana, E. J., Rey, G. J. F. D., et al. (2000) · The Clinical Neuropsychologist · doi:10.1076/1385-4046(200002)14:1;1-8;ft093 · Cited by 8 · see citing works
Behavior as an efficacy outcome.
Jl, C. (1997) · PubMed · Cited by 2 · see citing works
Winblad (1999) · doi:10.1002/(sici)1099-1166(199902)14:2
Flagged first, then by citations
Cited by
Sorted by citations
The Alzheimer’s Disease Clinical Spectrum
Atri, A. (2019) · Medical Clinics of North America · doi:10.1016/j.mcna.2018.10.009 · Cited by 623 · see citing works
Olivares, D., K. Deshpande, V., Shi, Y., K. Lahiri, D., H. Greig, N., T. Rogers, J., & Huang, X. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322564 · Cited by 407 · see citing works
Current and future treatments in Alzheimer’s disease
Atri, A. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1678581 · Cited by 309 · see citing works
Combination Drug Therapy for the Management of Alzheimer’s Disease
Kabir, M. T., Uddin, M. S., Mamun, A. A., Jeandet, P., Aleya, L., Mansouri, R. A., Ashraf, G. M., Mathew, B., Bin-Jumah, M. N., & Abdel-Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093272 · Cited by 217 · see citing works
Grossberg, G., & Thomas, S. (2009) · Clinical Interventions in Aging · doi:10.2147/cia.s6666 · Cited by 151 · see citing works
- Authors
- Grossberg, G. T., Pejović, V., Miller, M. L., & Graham, S. M.
- Affiliations
- Saint Louis University (US)
- Forest Laboratories (United States) (US)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 27
- Issue
- 2
- Pages
- 164-172
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2041601072
- Cited by
- 59
- References
- 68
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 4 · 2012: 10
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Forest Research Institute
- Forest Laboratories
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- memantine, Alzheimer's disease, behavioral symptoms, NMDA receptor antagonists, agitation, aggression, community-dwelling patients, moderate to severe dementia
- MeSH terms
- Aged, Alzheimer Disease, Behavior, Female, Humans, Male, Memantine, Neuropsychological Tests, Randomized Controlled Trials as Topic, Treatment Outcome, Excitatory Amino Acid Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
