CNS Drugs

, Volume 25, Issue 5, pp 425–433 | Cite as

Changes in Nursing Burden Following Memantine for Agitation and Aggression in Long-Term Care Residents with Moderate to Severe Alzheimer’s Disease

An Open-Label Pilot Study
  • Nathan Herrmann
  • Jaclyn Cappell
  • Goran M. Eryavec
  • Krista L. Lanctôt
Original Research Article


Background: Agitation and aggression are common neuropsychiatric symptoms of Alzheimer’s disease (AD) with a negative impact on caregivers.

Objective: The aim of the study was to determine whether changes in agitation and aggression would follow memantine treatment and, if so, be associated with changes in nursing burden in institutionalized patients with moderate to severe AD.

Study Design: This was a 3-month open-label trial of memantine.

Setting: The setting was two long-term care facilities.

Patients: Thirty-one institutionalized patients with moderate to severe AD and significant behavioural and psychiatric symptoms were included in the study.

Intervention: Memantine was titrated to a target dose of 10mg twice daily.

Main Outcome Measure: Effectiveness was assessed by the change in the Neuropsychiatric Inventory-Nursing Home (NPI-NH) agitation/aggression subscale and Clinical Global Impression of Change (CGI-C) scale using the intent-to-treat population. To establish caregiver impact, the effect on nursing burden was measured by the Modified Nursing Care Assessment Scale (primary outcome). As a secondary analysis, the caregiver distress subscale of the NPI-NH was examined, as well as changes in as required (pro re nata [prn]) psychotropic medication use.

Results: Twenty-four patients completed the study. A significant decrease in agitation and aggression (F-test with 3 and 90 degrees of freedom [F3.90] = 3.721, p = 0.014) was demonstrated following memantine, with 48% of patients improving (either much improved or minimally improved) on the CGI-C scale. In addition, nursing burden (t-test with 30 degrees of freedom [t30] = 3.02, p = 0.005), caregiver distress (F3.90 = 4.125, p = 0.009) and the use of prn psychotropics decreased following memantine treatment (Z = −1.99, p = 0.046). Fourteen patients experienced at least one adverse event during memantine treatment. The most common adverse event associated with treatment was somnolence (n = 5).

Conclusion: The results of this study suggest that the decreased agitated and aggressive behaviour in institutionalized patients with moderate to severe AD following treatment with memantine was accompanied by improvements in nursing burden and decreased psychotropic use. These findings should be confirmed in a larger, controlled trial. Identifier: NCT00401167



This research was supported by Lundbeck Canada, Inc. as an Investigator Initiated Trial. Dr Herrmann has received research support, consultation fees and speaker’s honoraria from Pfizer, Janssen-Ortho, Novartis, Lundbeck, Wyeth and Sonexa. In addition, Dr Herrmann is a co-investigator in an ongoing memantine clinical trial (Lundbeck Canada-NCT00857649). Jaclyn Cappell and Dr Eryavec have no conflicts of interest to declare. Dr Lanctôt has received research support, consultation fees and speaker’s honoraria from Abbott, Pfizer, Janssen-Ortho, Lundbeck, Wyeth and Sonexa.


  1. 1.
    Tariot PN. Medical management of advanced dementia. J Am Geriatr Soc 2003 May; 51(5 Suppl. Dementia): S305–13PubMedCrossRefGoogle Scholar
  2. 2.
    The incidence of dementia in Canada. Neurology 2000 Jul 12; 55 (1): 66–73Google Scholar
  3. 3.
    Matsumoto N, Ikeda M, Fukuhara R, et al. Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community. Dement Geriatr Cogn Disord 2007; 23(4): 219–24PubMedCrossRefGoogle Scholar
  4. 4.
    Hurt C, Bhattacharyya S, Burns A, et al. Patient and caregiver perspectives of quality of life in dementia: an investigation of the relationship to behavioural and psychological symptoms in dementia. Dement Geriatr Cogn Disord 2008; 26(2): 138–46PubMedCrossRefGoogle Scholar
  5. 5.
    Buhr GT, White HK. Difficult behaviors in long-term care patients with dementia. J Am Med Dir Assoc 2006 Mar; 7(3): 180–92PubMedCrossRefGoogle Scholar
  6. 6.
    Keene J, Hope T, Fairburn CG, et al. Natural history of aggressive behaviour in dementia. Int J Geriatr Psychiatry 1999 Jul; 14(7): 541–8PubMedCrossRefGoogle Scholar
  7. 7.
    Evans LK, Strumpf NE. Tying down the elderly: a review of the literature on physical restraint. J Am Geriatr Soc 1989 Jan; 37(1): 65–74PubMedGoogle Scholar
  8. 8.
    Marx MS, Cohen-Mansfield J, Werner P. Agitation and falls in institutionalized elderly persons. J Appl Gerontol 1990 Mar; 9(1): 106–17PubMedCrossRefGoogle Scholar
  9. 9.
    Lopez OL, Wisniewski SR, Becker JT, et al. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol 1999 Oct; 56(10): 1266–72PubMedCrossRefGoogle Scholar
  10. 10.
    Moritz DJ, Fox PJ, Luscombe FA, et al. Neurological and psychiatric predictors of mortality in patients with Alzheimer disease in California. Arch Neurol 1997 Jul; 54(7): 878–85PubMedCrossRefGoogle Scholar
  11. 11.
    Herrmann N, Lanctot KL, Sambrook R, et al. The contribution of neuropsychiatric symptoms to the cost of dementia care. Int J Geriatr Psychiatry 2006 Oct; 21(10): 972–6PubMedCrossRefGoogle Scholar
  12. 12.
    Herrmann N, Lanctot KL. Do atypical antipsychotics cause stroke? CNS Drugs 2005; 19(2): 91–103PubMedCrossRefGoogle Scholar
  13. 13.
    Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev 2006; (1): CD003476Google Scholar
  14. 14.
    Zheng L, Mack WJ, Dagerman KS, et al. Metabolic changes associated with second-generation antipsychotic use in Alzheimer’s disease patients: the CATIE-AD study. Am J Psychiatry 2009 May; 166(5): 583–90PubMedCrossRefGoogle Scholar
  15. 15.
    Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005 Oct 19; 294(15): 1934–43PubMedCrossRefGoogle Scholar
  16. 16.
    Kuehn BM. FDA warns antipsychotic drugs may be risky for elderly. JAMA 2005 May 25; 293(20): 2462PubMedCrossRefGoogle Scholar
  17. 17.
    Winblad B, Poritis N. Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 1999 Feb; 14(2): 135–46PubMedCrossRefGoogle Scholar
  18. 18.
    Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003 Apr 3; 348(14): 1333–41PubMedCrossRefGoogle Scholar
  19. 19.
    Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004 Jan 21; 291(3): 317–24PubMedCrossRefGoogle Scholar
  20. 20.
    van Dyck CH, Tariot PN, Meyers B, et al. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord 2007 Apr–Jun; 21(2): 136–43PubMedCrossRefGoogle Scholar
  21. 21.
    Wilcock GK, Ballard CG, Cooper JA, et al. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry 2008 Mar; 69(3): 341–8PubMedCrossRefGoogle Scholar
  22. 22.
    Gauthier S, Loft H, Cummings J. Improvement in behavioural symptoms in patients with moderate to severe Alzheimer’s disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry 2008 May; 23(5): 537–45PubMedCrossRefGoogle Scholar
  23. 23.
    van der Kam P, Mol F, Wimmers M. Beoordelingsschaal voor patienten (BOP). Deventer, The Netherlands: Van Loghum Slaterus, 1971Google Scholar
  24. 24.
    Zuidema SU, Derksen E, Verhey FR, et al. Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia. Int J Geriatr Psychiatry 2007 Jul; 22(7): 632–8PubMedCrossRefGoogle Scholar
  25. 25.
    Schneider LS, Olin JT, Doody RS, et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change: the Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11 Suppl. s2: S22–32PubMedCrossRefGoogle Scholar
  26. 26.
    Cohen-Mansfield J. Agitation in the elderly. Adv Psychosom Med 1989; 19: 101–13PubMedGoogle Scholar
  27. 27.
    Kleinman L, Frank L, Ciesla G, et al. Psychometric performance of an assessment scale for strain in nursing care: the M-NCAS. Health Qual Life Outcomes 2004; 2: 62PubMedCrossRefGoogle Scholar
  28. 28.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975 Nov; 12(3): 189–98PubMedCrossRefGoogle Scholar
  29. 29.
    Galasko D, Schmitt F, Thomas R, et al. Detailed assessment of activities of daily living in moderate to severe Alzheimer’s disease. J Int Neuropsychol Soc 2005 Jul; 11(4): 446–53PubMedGoogle Scholar
  30. 30.
    Weiner MF, Martin-Cook K, Svetlik DA, et al. The Quality of Life in Late-Stage Dementia (QUALID) scale. J Am Med Dir Assoc 2000 May–Jun; 1(3): 114–6PubMedGoogle Scholar
  31. 31.
    Barber C, Iwai M. Role conflict and role ambiguity as predictors of burnout among staff caring for elderly dementia patients. J Gerontol Soc Work 1996; 26: 101–16CrossRefGoogle Scholar
  32. 32.
    Cullen A. Burnout: why do we blame the nurse? Am J Nurs 1995 Nov; 95(11): 22–7; quiz 8PubMedCrossRefGoogle Scholar
  33. 33.
    Mitchell SL, Morris JN, Park PS, et al. Terminal care for persons with advanced dementia in the nursing home and home care settings. J Palliat Med 2004 Dec; 7(6): 808–16PubMedCrossRefGoogle Scholar
  34. 34.
    Gambassi G, Landi F, Lapane KL, et al. Predictors of mortality in patients with Alzheimer’s disease living in nursing homes. J Neurol Neurosurg Psychiatry 1999 Jul; 67(1): 59–65PubMedCrossRefGoogle Scholar
  35. 35.
    Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med 2009 Oct 15; 361(16): 1529–38PubMedCrossRefGoogle Scholar
  36. 36.
    Cohen-Mansfield J, Marx MS, Werner P. Agitation in elderly persons: an integrative report of findings in a nursing home. Int Psychogeriatr 1992; 4 Suppl. 2: 221–40PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Nathan Herrmann
    • 1
    • 2
  • Jaclyn Cappell
    • 2
  • Goran M. Eryavec
    • 3
  • Krista L. Lanctôt
    • 1
    • 2
    • 4
  1. 1.Department of PsychiatryUniversity of TorontoTorontoCanada
  2. 2.Sunnybrook Health Sciences CentreTorontoCanada
  3. 3.North York General HospitalTorontoCanada
  4. 4.Department of Pharmacology and ToxicologyUniversity of TorontoTorontoCanada

Personalised recommendations