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A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease

Published online by Cambridge University Press:  08 March 2013

Nathan Herrmann ,
Serge Gauthier ,
Neli Boneva  and
Ole Michael Lemming
Nathan Herrmann*
Affiliation:
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
Serge Gauthier
Affiliation:
McGill Centre for Studies in Aging, Alzheimer's Disease Research Unit, Montreal, Quebec, Canada Douglas Mental Health Research Institute, Montreal, Quebec, Canada
Neli Boneva
Affiliation:
H. Lundbeck A/S, Valby, Denmark
Ole Michael Lemming
Affiliation:
H. Lundbeck A/S, Valby, Denmark
*
Correspondence should be addressed to: Dr Nathan Herrmann, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, FG08, Toronto, Ontario M4N 3M5, Canada. Phone: +416-480-6133; Fax: +416-480-6022. Email: [email protected].
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Abstract

Background: Agitation and aggression in Alzheimer's disease (AD) are amongst the most serious of neuropsychiatric symptoms, and contribute to poor outcomes and worse quality of life. Previous studies have suggested a benefit for memantine on agitation and aggression, but none have examined its efficacy in community-dwelling patients with significant agitation and aggression at baseline, utilizing these behaviors as a primary outcome measure.

Methods: Patients with moderate-to-severe AD with Neuropsychiatric Inventory (NPI) total score ≥13 and NPI agitation/aggression score ≥1 were randomized to placebo or 20-mg memantine in a double-blind, 24-week trial. Co-primary outcome measures were behavior, measured by total NPI score, and cognition, using the Severe Impairment Battery (SIB). Secondary outcome measures included global assessment, function and other measures of behavior. This trial was registered as Clinicaltrials.gov: NCT00857649.

Results: A total of 369 patients (average age = 75, average MMSE = 12) were randomized to placebo or memantine. The study was prematurely terminated due to recruitment problems. There were no statistically significant differences between memantine and placebo in mean change from baseline in NPI, SIB, or any of the secondary outcome measures. Behavior improved in both groups (total NPI change scores −3.90 ± 1.24 for memantine and −5.13 ± 1.23 for placebo). Memantine was generally well tolerated and patient retention in both treatment arms was good.

Conclusions: The study failed to show the superiority of memantine in this sample of patients with moderate-to-severe AD with significant baseline agitation and aggression. Methodological limitations could have contributed to these results.

Keywords

memantineAlzheimer's diseaseagitationaggressionbehaviorrandomized controlled trial
Type
Research Article
Information
International Psychogeriatrics , Volume 25 , Issue 6 , June 2013 , pp. 919 - 927
Copyright
Copyright © International Psychogeriatric Association 2013

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References

Ballard, C., Corbett, A., Chitramohan, R. and Aarsland, D. (2009). Management of agitation and aggression associated with Alzheimer's disease: controversies and possible solutions. Current Opinion in Psychiatry, 22, 532–540. doi:10.1097/YCO.0b013e32833111f9.CrossRefGoogle ScholarPubMed
Cohen-Mansfield, J. (1989). Agitation in the elderly. Advances in Psychosomatic Medicine, 19, 101–113.CrossRefGoogle ScholarPubMed
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A. and Gornbein, J. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308–2314.CrossRefGoogle ScholarPubMed
Cummings, J. L., Schneider, E., Tariot, P. N., Graham, S. M. and Memantine MEM-MD-02 Study Group (2006). Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology, 67, 57–63.CrossRefGoogle ScholarPubMed
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle ScholarPubMed
Fox, C.et al. (2012). Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. PLoS ONE, 7, e35185. doi:10.1371/journal.pone.0035185.CrossRefGoogle ScholarPubMed
Galasko, D.et al. (1997). An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Disease and Associated Disorders, 11 (Suppl. 2), S33–S39.CrossRefGoogle ScholarPubMed
Gauthier, S.et al. (2002). Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. International Psychogeriatrics, 14, 389–404.Google ScholarPubMed
Gauthier, S., Loft, H. and Cummings, J. (2008). Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis. International Journal of Geriatric Psychiatry, 23, 537–545.CrossRefGoogle ScholarPubMed
Gauthier, S.et al. (2010). Management of behavioral problems in Alzheimer's disease. International Psychogeriatrics, 22, 346–372. doi:10.1017/S1041610209991505.CrossRefGoogle ScholarPubMed
Hachinski, V. C.et al. (1975). Cerebral blood flow in dementia. Archives of Neurology, 32, 632–637.CrossRefGoogle ScholarPubMed
Herrmann, N. and Gauthier, S. (2008). Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease. CMAJ, 179, 1279–1287. doi:10.1503/cmaj.070804.CrossRefGoogle ScholarPubMed
Herrmann, N. and Lanctôt, K. L. (2007). Pharmacologic management of neuropsychiatric symptoms of Alzheimer disease. Canadian Journal of Psychiatry, 52, 630–646.CrossRefGoogle ScholarPubMed
Hort, J.et al. (2010). EFNS guidelines for the diagnosis and management of Alzheimer's disease. European Journal of Neurology, 17, 1236–1248. doi:10.1111/j.1468-1331.2010.03040.x.CrossRefGoogle ScholarPubMed
Howard, R. J.et al. (2007). Donepezil for the treatment of agitation in Alzheimer's disease. New England Journal of Medicine, 357, 1382–1392.CrossRefGoogle ScholarPubMed
Howard, R.et al. (2012). Donepezil and memantine for moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 366, 893–903. doi:10.1056/NEJMoa1106668.CrossRefGoogle ScholarPubMed
Ihl, R.et al. (2011). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer's disease and other dementias. World Journal of Biological Psychiatry, 12, 2–32. doi:10.3109/15622975.2010.538083.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
Panisset, M., Roudier, M., Saxton, J. and Boller, F. (1994). Severe impairment battery. A neuropsychological test for severely demented patients. Archives of Neurology, 51, 41–45.CrossRefGoogle ScholarPubMed
Rabins, P. V., Mace, N. L. and Lucas, M. J. (1982). The impact of dementia on the family. JAMA, 248, 333–335.CrossRefGoogle ScholarPubMed
Schneider, L. S.et al. (1997). Validity and reliability of the Alzheimer's Disease Cooperative Study – clinical global impression of change. The Alzheimer's Disease Cooperative Study. Alzheimer Disease and Associated Disorders, 11 (Suppl. 2), S22–S32.CrossRefGoogle ScholarPubMed
Seitz, D. P., Adunuri, N., Gill, S. S., Gruneir, A., Herrmann, N. and Rochon, P. (2011). Antidepressants for agitation and psychosis in dementia. Cochrane Database of Systematic Reviews, (2), CD008191. doi:10.1002/14651858.CD008191.pub2.Google Scholar
Tariot, P. N.et al. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA, 291, 317–324.CrossRefGoogle ScholarPubMed
Wilcock, G. K., Ballard, C. G., Cooper, J. A. and Loft, H. (2008). Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. Journal of Clinical Psychiatry, 69, 341–348.CrossRefGoogle ScholarPubMed