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Use of Antipsychotic Drugs in Patients with Alzheimer’s Disease Treated with Rivastigmine versus Donepezil

A Retrospective, Parallel-Cohort, Hypothesis-Generating Study

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Abstract

Background and Objective Rivastigmine and donepezil are two cholinesterase inhibitors (ChEIs) indicated for the treatment of mild-to-moderate Alzheimer’s disease. Dementia-related behavioural issues are typically managed by environmental modification and the use of psychotropics including anti-psychotic medications. However, ChEIs have also been associated with reductions in behavioural symptoms in Alzheimer’s disease patients. This retrospective, parallel-cohort, hypothesis-generating study investigated whether treatment with rivastigmine is associated with reduced prescription of antipsychotic medications compared with treatment with donepezil.

Methods A combined analysis of two claims databases was conducted. Patients were included if they had a diagnosis of Alzheimer’s disease and were newly initiated on either rivastigmine or donepezil. Patients with prior use of memantine and/or antipsychotics were excluded. Kaplan-Meier and Cox analyses were conducted to compare the rate of antipsychotic drug use between the rivastigmine and donepezil groups.

Results A total of 956 patients receiving rivastigmine and 12778 patients receiving donepezil formed the study population. Analysis revealed that 64 (6.7%) rivastigmine and 989 (7.7%) donepezil recipients received antipsychotic medications (log-rank test from Kaplan-Meier analysis, p = 0.2289). The Cox regression analysis showed that rivastigmine was associated with a statistically significant reduction in the prescription of antipsychotic drugs relative to donepezil (hazard ratio 0.73; p = 0.044). Older age, longer time between Alzheimer’s disease diagnosis and first ChEI dispensing, lower dose of ChEI at treatment initiation and the presence of baseline depression and neuropsychiatric symptoms were associated with a significantly increased likelihood of antipsychotic drug use.

Conclusions In this retrospective analysis, Alzheimer’s disease patients with no prior use of antipsychotics initiated on rivastigmine had a significantly lower rate of prescription of antipsychotic drugs than those treated with donepezil.

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References

  1. Mega MS, Cummings JL, Fiorello T, et al. The spectrum of behavioral changes in Alzheimer’s disease. Neurology 1996; 46: 130–5

    Article  PubMed  CAS  Google Scholar 

  2. Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment and psycho-pathology in dementia. Neurology 1994; 44: 2308–14

    Article  PubMed  CAS  Google Scholar 

  3. Evans DA, Funkenstein HH, Alberts MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 1989; 262(18): 2551–6

    Article  PubMed  CAS  Google Scholar 

  4. Miech RA, Breitner JC, Zandi PP, et al. Incidence of AD may decline in the early 90s for men, later for women: the Cache County Study. Neurology 2002; 58(2): 209–18

    Article  PubMed  CAS  Google Scholar 

  5. Gilley DW, McCann JJ, Bienias JL, et al. Caregiver psychological adjustment and institutionalization of persons with Alzheimer’s disease. J Aging Health 2005; 17: 172–89

    Article  PubMed  Google Scholar 

  6. Yaffe K, Fox P, Newcommer R, et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002; 287: 2090–7

    Article  PubMed  Google Scholar 

  7. Suh DC, Arcona S, Thomas SK, et al. Risk of antipsychotic drug use in patients with Alzheimer’s disease treated with rivastigmine. Drugs Aging 2004; 21(6): 395–403

    Article  PubMed  CAS  Google Scholar 

  8. Geldmacher DS, Frolich L, Doody RS, et al. Realistic expectations for treatment success in Alzheimer’s disease. J Nutr Health Aging 2006; 10(5): 417–29

    PubMed  CAS  Google Scholar 

  9. Fillit HM, Doody RS, Binaso K, et al. Recommendations for best practices in the treatment of Alzheimer’s disease in managed care. Am J Geriatr Pharmacother 2006; 4Suppl. A: S9–24

    Article  PubMed  Google Scholar 

  10. Rogers SL, Farlow MR, Doody RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 1998; 50: 136–45

    Article  PubMed  CAS  Google Scholar 

  11. Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Arch Intern Med 1998; 158: 1021–31

    Article  PubMed  CAS  Google Scholar 

  12. Rogers SL, Doody RS, Pratt RD, et al. Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study. Eur Neuropsychopharmacol 2000; 10(3): 195–203

    Article  PubMed  CAS  Google Scholar 

  13. Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998; 1: 55–65

    CAS  Google Scholar 

  14. Rösler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomized controlled trial. BMJ 1999; 318(7184): 633–8

    Article  PubMed  Google Scholar 

  15. Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD. Neurology 2000; 54(12): 2269–76

    Article  PubMed  CAS  Google Scholar 

  16. Raskind MA, Peskind ER, Wessel T, et al. Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 2000; 54(12): 2261–8

    Article  PubMed  CAS  Google Scholar 

  17. Reisberg B, Doody RS, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003; 348(14): 1333–41

    Article  PubMed  CAS  Google Scholar 

  18. 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; 291(3): 317–24

    Article  PubMed  CAS  Google Scholar 

  19. 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; 14(2): 135–46

    Article  PubMed  CAS  Google Scholar 

  20. Beier MT. Treatment strategies for the behavioral symptoms of Alzheimer’s disease: focus on early pharmacologic intervention. Pharmacotherapy 2007; 27(3): 399–411

    Article  PubMed  CAS  Google Scholar 

  21. Farlow M, Potkin S, Koumaras B, et al. Analysis of outcome in retrieved dropout patients in a rivastigmine vs placebo, 26-week, Alzheimer disease trial. Arch Neurol 2003; 60(6): 843–8

    Article  PubMed  Google Scholar 

  22. Gauthier S, Feldman H, Hecker J, et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer’s disease. Int Psychogeriatr 2002; 14(4): 389–404

    Article  PubMed  Google Scholar 

  23. Cummings JL, McRae T, Zhang R. Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. Am J Geriatr Psychiatry 2006; 14(7): 605–12

    Article  PubMed  Google Scholar 

  24. Cummings JL, Anand R, Koumaras B, et al. Rivastigmine provides behavioral benefits to Alzheimer’s disease patients residing in a nursing home: findings from a 26-week trial [abstract]. Neurology 2000; 54: A468–9

    Google Scholar 

  25. Cummings JK, Schneider L, Tariot PN, et al. Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer’s disease. Am J Psychiatry 2004; 161(3): 532–8

    Article  PubMed  Google Scholar 

  26. Wooltorton E. Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ 2002; 167: 1269–70

    PubMed  Google Scholar 

  27. Wooltorton E. Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. CMAJ 2004; 170: 1395

    Article  PubMed  Google Scholar 

  28. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293(5): 596–608

    Article  PubMed  CAS  Google Scholar 

  29. 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): CD003476

    Google Scholar 

  30. Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 2009; 8(2): 151–7

    Article  PubMed  CAS  Google Scholar 

  31. 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; 294: 1934–43

    Article  PubMed  CAS  Google Scholar 

  32. Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007; 176: 627–32

    Article  PubMed  Google Scholar 

  33. Center for Drug Evaluation and Research. FDA public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances [online]. Available from URL: http://www.fda.gov/cder/drug/advisory/antipsychotics.htm/ [Accessed 2010 Jan 18]

  34. Center for Drug Evaluation and Research. FDA information for healthcare professionals on antipsychotics [online]. Available from URL: http://www.fda.gov/CDER/drug/InfoSheets/HCP/antipsychotics_conventional.htm/ [Accessed 2010 Jan 18]

  35. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults. Arch Intern Med 2003; 163: 2716–24

    Article  PubMed  Google Scholar 

  36. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotics drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355(15): 1525–38

    Article  PubMed  CAS  Google Scholar 

  37. Rochon PA, Normand SL, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med 2008; 168(10): 1090–6

    Article  PubMed  Google Scholar 

  38. Narayanan S, Beusterien KM, Thomas SK, et al. Antipsychotic drug use among nursing home residents taking rivastigmine. J Am Med Dir Assoc 2006; 7: 12–6

    Article  PubMed  Google Scholar 

  39. Health Insurance Portability and Accountability Act, HR 3103/Pub. L. No. 104-191, 110 Stat. 1936 (1996)

  40. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Hyattsville (MD): National Center for Health Statistics (NCHS), Centers for Medicare and Medicaid Services, 2009 [online]. Available from URL: http://www.cdc.gov/nchs/icd/icd9cm.htm [Accessed 2010 Sep 10]

  41. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987; 40(5): 373–83

    Article  PubMed  CAS  Google Scholar 

  42. Scharre DW, Cummings JL. Chapter 35: dementia. In: Yoshikawa TT, Cobbs EL, Brummel-Smith K, editors. Practical ambulatory geriatrics. 2nd ed. St Louis (MO): Mosby, 1998: 290–301

    Google Scholar 

  43. Fuschillo C, La Pia S, Campana F, et al. Cognitive deficits in Alzheimer’s disease: treatment with acetylcholinesterase inhibitor agents. Arch Gerontol Geriatr 2001; 33: 151–8

    Article  Google Scholar 

  44. Wilkinson DG, Passmore AP, Bullock R, et al. A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer’s disease. Int J Clin Pract 2002; 56: 441–6

    PubMed  CAS  Google Scholar 

  45. Takeda A, Loveman E, Clegg A, et al. A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer’s disease. Int J Geriatr Psychiatry 2006; 21(1): 9–13

    Article  Google Scholar 

  46. Wolfson C, Oremus M, Shukla V, et al. Donepezil and rivastigmine in the treatment of Alzheimer’s disease: a best-evidence synthesis of the published data on their efficacy and cost-effectiveness. Clin Ther 2002; 24(6): 862–86; discussion 837

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This research was funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Novartis manufactures rivastigmine. Francis Vekeman and Patrick Lefebvre are employees of Groupe d’Analyse, Ltée, which has received research grants from Novartis Pharmaceuticals Corporation. Mei Sheng Duh is an employee of Analysis Group, Inc., which has also received research grants from Novartis Pharmaceuticals Corporation. Analysis Group, Inc. and its Montreal office (Groupe d’Analyse, Ltée) were responsible for conducting the analyses. Nikita Mody-Patel was an employee of Novartis Pharmaceuticals Corporation at the time this manuscript was prepared. Kristijan H. Kahler is an employee and shareholder of Novartis Pharmaceuticals Corporation. Douglas W. Scharre has received research grants from Novartis Pharmaceuticals Corporation and has been a member of this company’s speaker’s bureau. He is also a paid consultant to Analysis Group, Inc. All authors contributed to the elaboration of the study design and the methodology, the interpretation of the results, and the development and writing of the draft manuscript, and have approved the current version.

Parts of this manuscript were presented at the 21st Annual Meeting & Showcase of the Academy of Managed Care Pharmacy, 15–18 April 2009, Orlando, Florida, USA.

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Authors and Affiliations

  1. Division of Cognitive Neurology, Department of Neurology, Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH, 43210, USA

    Douglas W. Scharre MD (Director)

  2. Groupe d’Analyse, Ltée, Montréal, Québec, Canada

    Francis Vekeman & Patrick Lefebvre

  3. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

    Nikita Mody-Patel & Kristijan H. Kahler

  4. Analysis Group, Inc., Boston, Massachusetts, USA

    Mei Sheng Duh

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Scharre, D.W., Vekeman, F., Lefebvre, P. et al. Use of Antipsychotic Drugs in Patients with Alzheimer’s Disease Treated with Rivastigmine versus Donepezil. Drugs Aging 27, 903–913 (2010). https://doi.org/10.2165/11584290-000000000-00000

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