Clinical Drug Investigation

, Volume 28, Issue 5, pp 291–303 | Cite as

A Markov Model of the Cost Effectiveness of Olanzapine Treatment for Agitation and Psychosis in Alzheimer’s Disease

  • Stephanie Kirbach
  • Kit Simpson
  • Paul J. Nietert
  • Jacobo Mintzer
Original Research Article

Abstract

Background and objective:

Antipsychotics have long been used to treat agitation and psychosis related to Alzheimer’s disease, but in a limited fashion because of troubling adverse effects. The new atypical antipsychotics are thought to be at least as effective as first-generation drugs and to cause fewer adverse effects. These drugs, however, are currently not US FDA-approved for use among elderly demented subjects due to a slight increase in the risk of death and serious cardiovascular events within this population. However, their favourable adverse effect profile has led many physicians to prescribe these drugs as first-line therapy for behaviourally disturbed patients with Alzheimer’s disease. Clinical trials to evaluate the use of atypical antipsychotics have produced varying results, and clarity has not yet been achieved. Thus, a quantitative summary of the risks and benefits may help inform complex decisions that must be made in this area. In this study we set out to compare the expected costs and outcomes for a community-dwelling cohort of patients with Alzheimer’s disease with agitation and/or psychosis who are (a) untreated, or (b) treated with olanzapine.

Methods:

We constructed a Markov state-transition model using the best published data from several sources for Alzheimer’s disease patient progression and treatment. This model allowed us to compare the expected costs and outcomes associated with olanzapine treatment compared with no treatment for a synthetic cohort of US adults aged ≥65 years. The model cycles every 6 months and continues until all patients die from Alzheimer’s disease progression or from co-morbid conditions. Outcome estimates included the incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. The robustness of the estimates was examined by sensitivity analyses of key parameters, including cost of care, olanzapine effectiveness and Alzheimer’s disease progression rates.

Results:

Results indicated that olanzapine was a cost-effective treatment for agitation and psychosis related to Alzheimer’s disease when compared with no treatment (ICER <$US50 000). In addition, sensitivity analyses demonstrated that olanzapine remained cost effective despite multiple variations of several parameters, both alone and concurrently.

Conclusion:

Olanzapine treatment for agitation and psychosis related to Alzheimer’s disease is cost effective when compared with no treatment. Further analysis should be performed as atypical antipsychotics become generic, as more information on health utilities in the Alzheimer’s disease population becomes available, and to compare atypical antipsychotics with first-generation antipsychotics.

References

  1. 1.
    Chung J, Cummings J. Neurobehavioral and neuropsychiatric symptoms in Alzheimer’s disease: characteristics and treatment. Neurol Clin 2007; 18: 1–16Google Scholar
  2. 2.
    Scarmeas N, Brandt J, Albert M, et al. Delusions and hallucinations are associated with worse outcomes in Alzheimer’s disease. Arch Neurol 2005; 62: 1601–8PubMedCrossRefGoogle Scholar
  3. 3.
    Alzheimer’s Association. 2007 Alzheimer’s disease facts and figures [online]. Available from URL: http://www.alz.org/national/documents/Report_2007FactsAndFigures.pdf [Accessed 2007 May 7]
  4. 4.
    Lopez O, Wisniewski S, Becker J, et al. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer’s disease. Arch Neurol 1999; 56: 1266–72PubMedCrossRefGoogle Scholar
  5. 5.
    Devanand D, Jacobs D, Tang M, et al. The course of psycho- pathologic features in mild to moderate Alzheimer’s disease. Arch Gen Psychiatry 1997; 54: 257–63PubMedCrossRefGoogle Scholar
  6. 6.
    Coyne A, Reichman W, Berbig L. The relationship between dementia and elder abuse. Am J Psychiatry 2003; 150: 643–6Google Scholar
  7. 7.
    Schneider L, Dagerman K, Insel P. Efficacy and adverse effects of atypical anti-psychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006; 14(3): 191–210PubMedGoogle Scholar
  8. 8.
    Tariot P, Schneider L, Katz I, et al. Quetiapine treatment of psychosis associated with dementia: a double-blind, randomized, placebo-controlled clinical trial. Am J Geriatr Psychiatry 2006; 14(9): 767–76PubMedCrossRefGoogle Scholar
  9. 9.
    Schneider L, Dagerman K, Insel P. Risk of death with atypical anti-psychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294: 1934–43PubMedCrossRefGoogle Scholar
  10. 10.
    Motsinger C, Perron G, Lacy T. Use of atypical anti-psychotic drugs in patients with dementia. Am Fam Physician 2003; 67: 2335–40PubMedGoogle Scholar
  11. 11.
    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): CD003476PubMedGoogle Scholar
  12. 12.
    Brodaty H, Ames D, Snowdon J, et al. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003; 64(2): 134–43PubMedCrossRefGoogle Scholar
  13. 13.
    Street J, Clark W, Gannon K, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities. Arch Gen Psychiatry 2000; 57: 968–76PubMedCrossRefGoogle Scholar
  14. 14.
    Beard S, Maciver F, Clouth J, et al. A decision model to compare health care costs of olanzapine and risperidone treatment for schizophrenia in Germany. Eur J Health Econ 2006; 7(3): 165–72PubMedCrossRefGoogle Scholar
  15. 15.
    Deberdt W, Dysken M, Rappaport S, et al. Comparison of olanzapine and risperidone in the treatment of psychosis and associated behavioral disturbances in patients with dementia. Am J Geriatr Psychiatry 2005; 13(8): 722–30PubMedGoogle Scholar
  16. 16.
    Suh G, Son H, Ju Y, et al. A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances. Am J Geriatr Psychiatry 2004; 12: 509–16PubMedGoogle Scholar
  17. 17.
    Alexopoulos G, Jeste D, Chung H, et al. The expert consensus guideline series: treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. Postgrad Med 2005; Spec. No.: 6-22Google Scholar
  18. 18.
    Mintzer J, Greenspan A, Caers I, et al. Risperidone in the treatment of psychosis in Alzheimer’s disease: results from a prospective clinical trial. Am J Geriatr Psychiatry 2006; 14(3): 280–91PubMedCrossRefGoogle Scholar
  19. 19.
    Schneider L, Tariot P, Dagerman K, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355(15): 1525–38PubMedCrossRefGoogle Scholar
  20. 20.
    Bernardo M, Azanza J, Rubio-Terres C, et al. Cost-effectiveness analysis of schizophrenia relapse prevention. Clin Drug Invest 2006; 26(8): 447–57CrossRefGoogle Scholar
  21. 21.
    Palmer C, Revicki D, Genduso L, et al. A cost-effectiveness clinical decision analysis model for schizophrenia. Am J Manag Care 1998; 4: 345–55PubMedGoogle Scholar
  22. 22.
    Chumney E, Simpson K. Cost-utility analysis. In: Chumney E, Simpson K, editors. Methods and designs for outcomes research. Bethesda (MD): American Society of Health-System Pharmacists, 2006: 151–5Google Scholar
  23. 23.
    Green C, Picot J, Loveman E, et al. Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer’s disease. Pharmacoeconomics 2006; 23(12): 1271–82CrossRefGoogle Scholar
  24. 24.
    Jones R, McCrone P, Guilaume C. Cost effectiveness of me-mantine in Alzheimer’s disease: an analysis based on a probabilistic Markov model from a UK perspective. Drugs Aging 2004; 21(9): 607–20PubMedCrossRefGoogle Scholar
  25. 25.
    Jonsson L. Cost-effectiveness of memantine for moderate to severe Alzheimer’s disease in Sweden. Am J Geriatr Pharmacother 2005; 3(2): 77–86PubMedCrossRefGoogle Scholar
  26. 26.
    Kirby J, Green C, Loveman E, et al. A systematic review of the clinical and cost-effectiveness of memantine in patients with moderately severe to severe Alzheimer’s disease. Drugs Aging 2006; 23(3): 227–40PubMedCrossRefGoogle Scholar
  27. 27.
    Almond S, O’Donnell O. Cost analysis of the treatment of schizophrenia in the UK: a comparison of olanzapine and haloperidol. Pharmacoeconomics 1998; 13(5 Pt 2): 575–88PubMedCrossRefGoogle Scholar
  28. 28.
    Almond S, O’Donnell O. Cost analysis of the treatment of schizophrenia in the UK: a simulation model comparing olanzapine, risperidone and haloperidol. Pharmacoeconomics 2000; 17(4): 383–9PubMedCrossRefGoogle Scholar
  29. 29.
    Russell L, Gold M, Siegel J, et al. The role of cost-effectiveness analysis in health and medicine. Panel on Cost-Effectiveness in Health and Medicine. JAMA 1996; 276(14): 1172–7PubMedCrossRefGoogle Scholar
  30. 30.
    Neumann P, Araki S, Arcelus A, et al. Measuring Alzheimer’s disease progression with transition probabilities: estimates from CERAD. Neurology 2001; 57: 957–64PubMedCrossRefGoogle Scholar
  31. 31.
    Morris J, Heyman A, Mohs R. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 1989; 39: 1159–65PubMedCrossRefGoogle Scholar
  32. 32.
    Tariot P, Mack J, Patterson M, et al. The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer’s Disease. Am J Psychiatry 1995; 152: 1349–57PubMedGoogle Scholar
  33. 33.
    Ryu SH, Katona C, Rive B, et al. Persistence of and changes in neuropsychiatric symptoms in Alzheimer disease over 6 months: the LASER-AD study. Am J Geriatr Psychiatry 2005; 13: 976–83PubMedGoogle Scholar
  34. 34.
    Holtzer R, Tang MX, Devanand D, et al. Psychopathological features in Alzheimer’s disease: course and relationship with cognitive status. J Am Geriatr Soc 2003; 51(7): 953–60PubMedCrossRefGoogle Scholar
  35. 35.
    Lopez O, Becker J, Sweet R, et al. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer’s disease. J Neuropsychiatry Clin Neurosci 2003; 15: 346–53PubMedCrossRefGoogle Scholar
  36. 36.
    Cohen-Mansfield J, Marx M, Lipson S, et al. Predictors of mortality in nursing home residents. J Clin Epidemiol 1999; 52(4): 273–80PubMedCrossRefGoogle Scholar
  37. 37.
    Chaussalet T, Thompson W. Data requirements in a model of the natural history of Alzheimer’s disease. Health Care Manag Sci 2001; 4: 13–9PubMedCrossRefGoogle Scholar
  38. 38.
    Murman D, Chen Q, Powell M, et al. The incremental direct costs associated with behavioral symptoms in AD. Neurology 2002; 59: 1721–9PubMedCrossRefGoogle Scholar
  39. 39.
    Jonsson L, Jonhagen M, Kilander L, et al. Determinants of cost of care for patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2006; 21: 449–59PubMedCrossRefGoogle Scholar
  40. 40.
    Fleming, T. Red Book. Montvale (NJ): Thomson Publishers, 2006Google Scholar
  41. 41.
    CareScout. Genworth Financial 2007 cost of care survey [online]. Available from URL: http://longtermcare.genworth.com/comweb/consumer/pdfs/longtermcare/CostOf_Care_Survey.pdf [Accessed 2007 May 7]
  42. 42.
    US Department of Labor: Bureau of Labor Statistics CPI Inflation calculator (nd) [online]. Available from URL: http://data.bls.gov/cgi-bin/cpicalc.pl [Accessed 2007 May 7]
  43. 43.
    Murman D, Colenda C. The economic impact of neuropsychiatric symptoms in Alzheimer’s disease: can drugs ease the burden? Pharmacoeconomics 2005; 23(3): 227–42PubMedCrossRefGoogle Scholar
  44. 44.
    Neumann P, Sandberg E, Araki S. A comparison of HUI2 and HUI3 utility scores in Alzheimer’s disease. Med Decis Making 2000; 20: 413–22PubMedCrossRefGoogle Scholar
  45. 45.
    Rosencheck R, Leslie D, Sindelar J, et al. Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia. Am J Geriatr Psychiatry 2006; 163(12): 2080–9Google Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Stephanie Kirbach
    • 1
  • Kit Simpson
    • 2
  • Paul J. Nietert
    • 1
  • Jacobo Mintzer
    • 3
  1. 1.Department of Biostatistics, Bioinformatics and EpidemiologyMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Health Administration and PolicyMedical University of South CarolinaCharlestonUSA
  3. 3.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA

Personalised recommendations