Drugs & Aging

, Volume 29, Issue 10, pp 807–817 | Cite as

Comparative Risk of Cerebrovascular Adverse Events in Community-Dwelling Older Adults using Risperidone, Olanzapine and Quetiapine

A Multiple Propensity Score-Adjusted Retrospective Cohort Study
  • Satabdi Chatterjee
  • Hua Chen
  • Michael L. Johnson
  • Rajender R. Aparasu
Original Research Article

Abstract

Background

Atypical antipsychotic agents have been associated with cerebrovascular adverse events, particularly in elderly dementia patients. However, limited evidence exists regarding comparative cerebrovascular profiles of individual atypical agents, particularly in community settings.

Objective

The objective of this study was to evaluate the risk of cerebrovascular events associated with use of risperidone, olanzapine and quetiapine in community-dwelling older adults in the US.

Methods

A propensity score-adjusted retrospective cohort design involving the IMS LifeLink™ Health Plan Claims Database was used for the study. The study population included all older adults (aged ≥50 years) who initiated risperidone, olanzapine or quetiapine anytime during 1 July 2000 to 30 June 2008. Patients were followed until hospitalization or an emergency room visit for a cerebrovascular event, or the end of the study period, whichever occurred earlier. The Cox proportional hazard regression model with time-varying covariates was used to evaluate the risk of cerebrovascular events during the follow-up period, using olanzapine as the reference. The covariates adjusted for in the final model included multiple propensity scores and exposure to other medications that could be associated with the risk of cerebrovascular events.

Results

A total of 2,458 cerebrovascular events were identified in the study cohort: 1,081 (21.38 %) for risperidone users, 816 (18.75 %) for olanzapine users and 561 (21.05 %) for quetiapine users. After adjusting for propensity scores and other covariates, the Cox proportional hazard model revealed that use of quetiapine [hazard ratio (HR) 0.88; 95 % CI 0.78, 0.99] but not risperidone (HR 1.05; 95 % CI 0.95, 1.16) was associated with a decrease in the risk of cerebrovascular adverse events compared with olanzapine.

Conclusions

The study suggested that quetiapine use may be associated with a moderately lower risk of cerebrovascular events than olanzapine in older adults. Prescribers should closely monitor the patients treated with atypical agents for the incidence of cerebrovascular adverse events.

Notes

Acknowledgments

The statements, findings, conclusions, views and opinions contained and expressed in this article are based in part on data obtained under license from the IMS LifeLink™ Health Plan Claims Database (1999–2003), IMS Health Incorporated. All rights reserved. The statements, findings, conclusions, views and opinions contained and expressed herein are not necessarily those of IMS Health Incorporated or any of its affiliated or subsidiary entities. The authors have no conflicts of interest to disclose that are directly relevant to the content of this study. No sources of funding were received to conduct this study.

References

  1. 1.
    Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373:31–41.PubMedCrossRefGoogle Scholar
  2. 2.
    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
  3. 3.
    Cuesta MJ, Peralta V, Zarzuela A. Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study. Schizophr Res. 2001;48:17–28.PubMedCrossRefGoogle Scholar
  4. 4.
    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(15):1934–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Recupero PR, Rainey SE. Managing risk when considering the use of atypical antipsychotics for elderly patients with dementia-related psychosis. J Psychiatr Pract. 2007;13(3):143–52.PubMedCrossRefGoogle Scholar
  6. 6.
    Gareri P, De Fazio P, De Fazio S, Marigliano N, Ferreri Ibbadu G, De Sarro G. Adverse effects of atypical antipsychotics in the elderly: a review. Drugs Aging. 2006;23(12):937–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Jano E, Johnson M, Chen H, Aparasu RR. Determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly, 1996–2004. Curr Med Res Opin. 2008;24(3):709–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Kleijer BC, van Marum RJ, Egberts AC, Jansen PA, Knol W, Heerdink ER. Risk of cerebrovascular events in elderly users of antipsychotics. J Psychopharmacol. 2009;23(8):909–14.Google Scholar
  9. 9.
    Smith D, Beier M. Association between risperidone treatment and cerebrovascular adverse events: examining the evidence and postulating hypotheses for an underlying mechanism. J Am Med Dir Assoc. 2004;5(2):129–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Wooltorton E. Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ. 2002;167(11):1269–70.PubMedGoogle Scholar
  11. 11.
    Wooltorton E. Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. CMAJ. 2004;170(9):1395.PubMedGoogle Scholar
  12. 12.
    Brodaty H, Ames D, Snowdon J, Woodward M, Kirwan J, Clarnette R, 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):134–43.PubMedCrossRefGoogle Scholar
  13. 13.
    Herrmann N, Lanctôt KL. Do atypical antipsychotics cause stroke? CNS Drugs. 2005;19(2):91–103.PubMedCrossRefGoogle Scholar
  14. 14.
    Street JS, Clark WS, Gannon KS, Cummings JL, Bymaster FP, Tamura RN, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry. 2000;57(10):968–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Finkel S, Kozma C, Long S, Greenspan A, Mahmoud R, Baser O, et al. Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics. Int Psychogeriatr. 2005;17(4):617–29.PubMedCrossRefGoogle Scholar
  16. 16.
    Gill SS, Rochon PA, Herrmann N, Lee PE, Sykora K, Gunraj N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ. 2005;330(7489):445.PubMedCrossRefGoogle Scholar
  17. 17.
    Herrmann N, Mamdani M, Lanctôt KL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry. 2004;161(6):1113–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Liperoti R, Gambassi G, Lapane KL, Chiang C, Pedone C, Mor V, et al. Cerebrovascular events among elderly nursing home patients treated with conventional or atypical antipsychotics. J Clin Psychiatry. 2005;66:1090–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Layton D, Harris S, Wilton LV, Shakir SAW. Comparison of incidence rates of cerebrovascular accidents and transient ischaemic attacks in observational cohort studies of patients prescribed risperidone, quetiapine or olanzapine in general practice in England including patients with dementia. J Psychopharmacol. 2005;19(5):473–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Barnett M, Wehrig H, Perry PJ. Comparison of risk of cerebrovascular events in an elderly VA population with dementia between antipsychotic and nonantipsychotic users. J Clin Psychopharmacol. 2007;27:595–601.PubMedCrossRefGoogle Scholar
  21. 21.
    Perccudani M, Barbui C, Fortino I, Tansella M, Petrovich L. Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly. J Clin Psychopharmacol. 2005;25:468–70.CrossRefGoogle Scholar
  22. 22.
    Mehta S, Johnson ML, Chen H, Aparasu RR. Risk of cerebrovascular adverse events in older adults using antipsychotic agents: a propensity-matched retrospective cohort study. J Clin Psychiatry. 2010;71(6):689–98.PubMedCrossRefGoogle Scholar
  23. 23.
    Ray W. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158:915–20.PubMedCrossRefGoogle Scholar
  24. 24.
    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(5):627–32.PubMedGoogle Scholar
  25. 25.
    Agency for Healthcare Research and Quality Center for Cost and Financing Studies. MEPS HC-052. 2000 medical conditions. June 2003. http://www.meps.ahrq.gov/mepsweb/data_stats/download_data/pufs/h52/h52doc.pdf. Accessed 2009 Apr 16.
  26. 26.
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41–55.CrossRefGoogle Scholar
  27. 27.
    Austin PC. The performance of different propensity-score methods for estimating differences in proportions (risk differences or absolute risk reductions) in observational studies. Stat Med. 2010;29(20):2137–48.PubMedCrossRefGoogle Scholar
  28. 28.
    Weitzen S, Lapane KL, Toledano AY, Hume AL, Mor V. Principles for modeling propensity scores in medical research: a systematic literature review. Pharmacoepidemiol Drug Saf. 2004;13(12):841–53.PubMedCrossRefGoogle Scholar
  29. 29.
    Shah BR, Laupacis A, Hux JE, Austin PC. Propensity score methods gave similar results to traditional regression modeling in observational studies: a systematic review. J Clin Epidemiol. 2005;58(6):550–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Spreeuwenberg MD, Bartak A, Croon MA, Hagenaars JA, Busschbach JJ, Andrea H, et al. The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care. 2010;48(2):166–74.PubMedCrossRefGoogle Scholar
  31. 31.
    Andersen R, Newman JF. Societal and individual determinants of medical care utilization in the United States. Milbank Mem Fund Q Health Soc. 1973;51(1):95–124.PubMedCrossRefGoogle Scholar
  32. 32.
    Aparasu RR, Jano E, Johnson ML, Chen H. Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients. Am J Geriatr Pharmacother. 2008;6(4):198–204.PubMedCrossRefGoogle Scholar
  33. 33.
    Imbens GW. The role of the propensity score in estimating dose–response functions. Biometrika. 2000;87:706–10.CrossRefGoogle Scholar
  34. 34.
    McFadden D, Train K, Tye W. An application of diagnostic tests for the independence from irrelevant alternatives property of the multinomial logit model. Transp Res Rec. 1976;637:39–45.Google Scholar
  35. 35.
    Furie KL, Kelly PJ. Handbook of stroke prevention in clinical practice. Totowa: Humana Press; 2004.CrossRefGoogle Scholar
  36. 36.
    Gottlieb S. Warnings issued over COX 2 inhibitors in US and UK. BMJ. 2005;330(9):4.Google Scholar
  37. 37.
    Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med. 1994;120(11):897–902.PubMedCrossRefGoogle Scholar
  38. 38.
    Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. The risk for and severity of bleeding complications in elderly patients treated with warfarin. Ann Intern Med. 1999;124(11):970–9.CrossRefGoogle Scholar
  39. 39.
    Stephenson J. FDA orders estrogen safety warnings: agency offers guidance for HRT use. JAMA. 2003;289(5):537–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Greenspan A, Eerdekens M, Mahmoud R. Is there an increased risk of cerebrovascular adverse events among dementia patients treated with risperidone? In: Proceedings of the annual meeting of the International College of Geriatric Psychoneuropharmacology, San Juan, 12–14 Dec 2003.Google Scholar
  41. 41.
    Greenspan A, Eerdekens M, Mahmoud R. Is there an increased rate of cerebrovascular adverse events with risperidone in patients with dementia? [abstract]. Int J Neuropsychopharmacol. 2004;7(Suppl. 1):S205.Google Scholar
  42. 42.
    Arnt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18:63–101.PubMedCrossRefGoogle Scholar
  43. 43.
    Hellewell JSE, Gerlach J. Opportunities and challenges presented by new generation antipsychotics. Int J Psych Clin Pract. 2000;4(Suppl 1):53–62.CrossRefGoogle Scholar
  44. 44.
    Hellewell JSE. Quetiapine: a well-tolerated and effective atypical antipsychotic. Hosp Med. 2002;63(10):600–3.PubMedGoogle Scholar
  45. 45.
    Perkins DO. Antipsychotic-induced hyperprolactinemia: pathophysiology and clinical consequences. Adv Stud Med. 2004;4(10F):S982–6.Google Scholar
  46. 46.
    Valuck RJ, Libby AM, Sills MR, Giese AA, Allen RR. Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study. CNS Drugs. 2004;18(15):1119–32.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  • Satabdi Chatterjee
    • 1
  • Hua Chen
    • 1
  • Michael L. Johnson
    • 1
  • Rajender R. Aparasu
    • 1
  1. 1.Department of Clinical Sciences and Administration, College of Pharmacy, Texas Medical CenterUniversity of HoustonHoustonUSA

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