Skip to main content
Log in

Cost Effectiveness of Memantine in Alzheimer’s Disease

An Analysis Based on a Probabilistic Markov Model from a UK Perspective

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background

Clinical trials with memantine, an uncompetitive moderate-affinity NMDA antagonist, have shown improved clinical outcomes, increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer’s disease. In a randomised double-blind, placebo-controlled, 28-week study conducted in the US, reductions in resource utilisation and total healthcare costs were noted with memantine relative to placebo. While these findings suggest that, compared with placebo, memantine provides cost savings, further analyses may help to quantify potential economic gains over a longer treatment period.

Objective

To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer’s disease over a 2-year period.

Methods

A Markov model was constructed to simulate patient progression through a series of health states related to severity, dependency (determined by patient scores on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living [ADCS-ADL] inventory and residential status (‘institutionalisation’) with a time horizon of 2 years (each 6-month Markov cycle was repeated four times). Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week, randomised, double-blind, placebo-controlled clinical trial. Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study, while data on quality-adjusted life-years (QALYs) were derived from a Danish longitudinal study. To ensure conservative estimates from the model, the base case analysis assumed drug effectiveness was limited to 12 months. Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model. Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters. Finally, a subgroup analysis was performed to determine which patients were most likely to benefit from memantine. Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective.

Results

The base case analysis found that, compared with no treatment, memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence, years in the community and QALYs. Sensitivity analyses supported these findings. For each category of Alzheimer’s disease patient examined, treatment with memantine was a cost-effective strategy. The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of ≥10.

Conclusion

This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment. These benefits appear to result from prolonged patient independence and delayed institution-alisation for moderately severe and severe Alzheimer’s disease patients on memantine compared with no pharmacological treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II
Table III
Table IV
Table V
Table VI
Table VII
Table VIII
Table IX

Similar content being viewed by others

References

  1. Knopman DS. The initial recognition and diagnosis of dementia. Am J Med 1998; 104(4A): 2–12S

    Article  Google Scholar 

  2. Migliaccio-Walle K, Getsios D, Caro J, et al. Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer’s disease in the United States. Clin Ther 2003; 25(6): 1806–25

    Article  PubMed  Google Scholar 

  3. Reisberg B, Burns A, Brodaty H, et al. Diagnosis of Alzheimer’s disease: report of an International Psychogeriatric Association Special Meeting Work Group under the co-sponsorship of Alzheimer’s Disease International, the European Federation of Neurological Societies, the World Health Organization and the World Psychiatric Association. Int Psychogeriatr 1997; 9Suppl. 1: 11–38

    Article  PubMed  Google Scholar 

  4. Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med 1999; 341(22): 1670–9

    Article  PubMed  CAS  Google Scholar 

  5. 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: 135–46

    Article  PubMed  CAS  Google Scholar 

  6. Wimo A, Winblad B, Aguero-Torres H, et al. The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 2003; 17(2): 63–7

    Article  PubMed  Google Scholar 

  7. Potkin SG. The ABC of Alzheimer’s disease: ADL and improving day-to-day functioning of patients. Int Psychogeriatr 2002; 14Suppl. 1: 7–26

    Article  PubMed  Google Scholar 

  8. Grossberg GT. The ABC of Alzheimer’s disease: behavioral symptoms and their treatment. Int Psychogeriatr 2002; 14Suppl. 1: 27–49

    Article  PubMed  Google Scholar 

  9. Kurz X, Scuvee-Moreau J, Rive B, et al. A new approach to the qualitative evaluation of functional disability in dementia. Int J Geriatr Psychiatry 2003; 18(11): 1050–5

    Article  PubMed  CAS  Google Scholar 

  10. Bullock R, Hammond G. Realistic expectations: the management of severe Alzheimer disease. Alzheimer Dis Assoc Disord 2003; 17Suppl. 3: S80–5

    Article  PubMed  Google Scholar 

  11. Bloom BS, de Pouvourville N, Straus WL. Cost of illness of Alzheimer’s disease: how useful are current estimates? Gerontologist 2003; 43(2): 158–64

    Article  PubMed  Google Scholar 

  12. Lowin A, Knapp M, McCrone P. Alzheimer’s disease in the UK: comparative evidence on cost of illness and volume of health services research funding. Int J Geriatr Psychiatry 2001; 16(12): 1143–8

    Article  PubMed  CAS  Google Scholar 

  13. Andersen CK, Lauridsen J, Andersen K, et al. Cost of dementia: impact of disease progression estimated in longitudinal data. Scand J Public Health 2003; 31(2): 119–25

    Article  PubMed  Google Scholar 

  14. Hux MJ, O’Brien BJ, Iskedjian M, et al. Relation between severity of Alzheimer’s disease and costs of caring. CMAJ 1998; 159(5): 457–65

    PubMed  CAS  Google Scholar 

  15. Leon J, Neumann PJ. The cost of Alzheimer’s disease in managed care: a cross-sectional study. Am J Manag Care 1999 Jul; 5(7): 867–77

    PubMed  CAS  Google Scholar 

  16. Souetre EJ, Qing W, Vigoureux I, et al. Economic analysis of Alzheimer’s disease in outpatients: impact of symptom severity. Int Psychogeriatr 1995; 7(1): 15–22

    Google Scholar 

  17. Souetre E, Thwaites RM, Yeardley HL. Economic impact of Alzheimer’s disease in the United Kingdom: cost of care and disease severity for non-institutionalised patients with Alzheimer’s disease. Br J Psychiatry 1999; 174: 51–5

    Article  PubMed  CAS  Google Scholar 

  18. Meek PD, McKeithan EK, Schumock GT. Economic considerations in Alzheimer’s disease. Pharmacotherapy 1998; 18 (2 Pt 2): 68–73S

    PubMed  CAS  Google Scholar 

  19. Michel JP, Zekry D, Mulligan R, et al. Economic considerations of Alzheimer’s disease and related disorders. Aging (Milano) 2001; 13(3): 255–60

    CAS  Google Scholar 

  20. Feldman H, Gauthier S, Hecker J, et al. Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer’s disease and the effect on caregiver burden. J Am Geriatr Soc 2003; 51(6): 737–44

    Article  PubMed  Google Scholar 

  21. Stewart A, Phillips R, Dempsey G. Pharmacotherapy for people with Alzheimer’s disease: a Markov-cycle evaluation of five years’ therapy using donepezil. Int J Geriatr Psychiatry 1998; 13(7): 445–53

    Article  PubMed  CAS  Google Scholar 

  22. Reisberg B, Doody R, Stoffler 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 

  23. Wimo A, Winblad B, Stoffler A, et al. Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer’s disease. Pharmacoeconomics 2003; 21(5): 327–40

    Article  PubMed  CAS  Google Scholar 

  24. Folstein M, Folstein S, McHugh P. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189–98

    Article  PubMed  CAS  Google Scholar 

  25. Galasko DR, Schmitt FA, Jin S, et al. Detailed assessment of cognition and activities of daily living in moderate to severe Alzheimer’s disease [abstract]. Neurobiol Aging 2000; 21Suppl. 1: S168

    Article  Google Scholar 

  26. Galasko D, Bennett D, Sano M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11Suppl. 2: S33–9

    Article  PubMed  Google Scholar 

  27. Aguero-Torres H, Qiu C, Winblad B, et al. Dementing disorders in the elderly: evolution of disease severity over 7 years. Alzheimer Dis Assoc Disord 2002; 16(4): 221–7

    Article  PubMed  Google Scholar 

  28. National Institute for Clinical Excellence. Guidance on the use of donepezil, rivastigmine and galantamine for the treatment of Alzheimer’s disease. London: National Institute for Clinical Excellence, 2001 Jan. Technology Appraisal Guidance No. 19

    Google Scholar 

  29. Paton J, Johnston K, Katona C, et al. What causes problems in Alzheimer’s disease: attributions by caregivers. Int J Geriatr Psychiatry 2004; 19: 527–32

    Article  PubMed  Google Scholar 

  30. Livingston G, Katona C, Roch B. A dependency model for patients with Alzheimer’s disease: its validation and relationship to the costs of care: the LASER-AD Study. Curr Med Res Opin 2004; 57: 1007–16

    Article  Google Scholar 

  31. Kronborg Andersen C, Sogaard J, Hansen E, et al. The cost of dementia in Denmark: the Odense Study. Dement Geriatr Cogn Disord 1999; 10(4): 295–304

    Article  PubMed  CAS  Google Scholar 

  32. Wolstenholme J, Fenn P, Gray A, et al. Estimating the relationship between disease progression and cost of care in dementia. Br J Psychiatry 2002; 181: 36–42

    Article  PubMed  CAS  Google Scholar 

  33. Neumann PJ, Sandberg EA, Araki SS, et al. A comparison of HUI2 and HUI3 utility scores in Alzheimer’s disease. Med Decis Making 2000; 20(4): 413–22

    Article  PubMed  CAS  Google Scholar 

  34. Briggs AH, Ades AE, Price MJ. Probabilistic sensitivity analysis for decision trees with multiple branches: use of the Dirichlet distribution in a Bayesian framework. Med Decis Making 2003; 23(4): 341–50

    Article  PubMed  Google Scholar 

  35. Rive B, Vercelletto M, Damier FD, et al. Memantine enhances autonomy in patients with moderately-severe to severe Alzheimer’s disease. Int J Geriatr Psych 2004; 19: 458–64

    Article  Google Scholar 

  36. Reisberg B, Mobius H, Stoffler A, et al. Long-term treatment with the NMDA antagonist memantine: results of a 24-week, open-label extension study in moderately severe to severe Alzheimer’s disease [abstract]. 8th International Conference on Alzheimer’s Disease and Related Disorders; 2000 Jul 20–25; Stockholm

  37. Netten A, Curtis L. Unit costs of health and social care 2000. Canterbury: Personal Social Services Research Unit, University of Kent, 2000

    Google Scholar 

  38. National Institute for Clinical Excellence. Incorporating health economics in guidelines and assessing resource impact. London: Guideline Development Methods: Information for National Collaborating Centres and Guideline Developers. National Institute for Clinical Excellence, 2004

    Google Scholar 

  39. Trabucchi M. An economic perspective on Alzheimer’s disease. J Geriatr Psychiatry Neurol 1999; 12(1): 29–38

    Article  PubMed  CAS  Google Scholar 

  40. Small GW, McDonnell DD, Brooks RL, et al. The impact of symptom severity on the cost of Alzheimer’s disease. J Am Geriatr Soc 2002; 50(2): 321–7

    Article  PubMed  Google Scholar 

  41. Gauthier S, Bodick N, Erzigkeit E, et al. Activities of daily living as an outcome measure in clinical trials of dementia drugs. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. Alzheimer Dis Assoc Disord 1997; 11Suppl. 3: 6–7

    PubMed  Google Scholar 

  42. Neumann PJ, Araki SS, Arcelus A, et al. Measuring Alzheimer’s disease progression with transition probabilities: estimates from CERAD. Neurology 2001; 57(6): 957–64

    Article  PubMed  CAS  Google Scholar 

  43. Canadian Coordinating Office for Health Technology Assessment. Guidelines of economic evaluation of Pharmaceuticals: methods and guidelines. Ottawa (ON): CCOHTA, 1997

    Google Scholar 

  44. McGregor M. Cost-utility analysis: use QALYs only with great caution. CMAJ 2003; 168(4): 433–4

    PubMed  Google Scholar 

  45. Ward A, Caro JJ, Getsios D, et al. Assessment of health economics in Alzheimer’s disease (AHEAD): treatment with galantamine in the UK. Int J Geriatr Psychiatry 2003; 18(8): 740–7

    Article  PubMed  CAS  Google Scholar 

  46. Getsios D, Caro JJ, Caro G, et al. Assessment of health economics in Alzheimer’s disease (AHEAD): galantamine treatment in Canada. Neurology 2001; 57(6): 972–8

    Article  PubMed  CAS  Google Scholar 

  47. Neumann PJ, Hermann RC, Kuntz KM, et al. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. Neurology 1999; 52(6): 1138–45

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The funding for this project was provided by Lundbeck A/S and Merz Pharmaceuticals GmbH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chantal Guilhaume.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, R.W., McCrone, P. & Guilhaume, C. Cost Effectiveness of Memantine in Alzheimer’s Disease. Drugs Aging 21, 607–620 (2004). https://doi.org/10.2165/00002512-200421090-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200421090-00005

Keywords

Navigation