Drugs & Aging

, Volume 14, Issue 3, pp 231–239

Epidemiology of Adverse Drug Reactions in the Elderly by Drug Class

Review Article


As the growth of the elderly population continues, the burden on the health care system and society will also increase. Since chronic diseases such as hypertension, coronary artery disease, arthritis, stroke, cancer and diabetes mellitus are more prevalent with age, the number of people with multiple chronic diseases will also increase. These patients are likely to be treated for some or all of their conditions with drug therapies. When used appropriately, drugs may be the single most important intervention in the care of an older patient, but when used inappropriately they no longer provide therapeutic benefit, and they may even endanger the health of an older patient by causing an adverse drug reaction (ADR).

Factors believed to be responsible for increased adverse reactions in elderly patients are polypharmacy (including prescription and over-the-counter medications), increased drug-drug interaction, pharmacokinetic changes, pharmacodynamic changes, the pathology of aging and compliance. The exact role that age plays in ADRs is not clear. This is in part because few older patients are included in the large randomised trials, and so much of the information used to ascertain the age-associated risks of drugs comes from observational studies. Although the interactions of aging, concurrent comorbidities and polypharmacy are known, older patients do appear to be at increased risk. Improvements in the management of drug therapies of older patients can lead to improvements in their overall health, functioning and safety, as well as providing potential benefits to society by ameliorating some of the burden of their health care.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ostrom JF, Hammarlund ER, Christensen DB, et al. Medication usage in an elderly population. Med Care 1985; 23: 157–64CrossRefPubMedGoogle Scholar
  2. 2.
    US Department of Health and Human Services. Healthy people 2000: National health promotion and disease prevention objectives. Washington, DC: Government Printing Office, 1991Google Scholar
  3. 3.
    Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Intern Med 1995; 155: 1949–56CrossRefPubMedGoogle Scholar
  4. 4.
    Classen DC, Pestotnik SL, Evans S, et al. Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277: 301–6CrossRefPubMedGoogle Scholar
  5. 5.
    Kannry JL, Chalmers TC, Orca M, et al. Neglect of aged in clinical trials [abstract]. Controlled Clin Trials 1989; 348Google Scholar
  6. 6.
    SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 263: 3255–64CrossRefGoogle Scholar
  7. 7.
    Collet JP, Boivin JF, Spitzer WO, et al. Bias and confounding in pharmacoepidemiology. New York: John Wiley and Sons, 1994: 609–27Google Scholar
  8. 8.
    Avorn J, Gurwitz J. Principles in pharmacology. In: Cassel CK, Reisenberg DE, Sorensen LB, et al. Geriatric medicine. New York: Springer-Verlag, 1990: 68–77Google Scholar
  9. 9.
    Gurwitz JH, Gore JM, Goldberg RJ, et al. Recent age-related trends in the use of thrombolytic therapy in patients who have had acute myocardial infarction. Ann Intern Med 1996; 124: 283–91PubMedGoogle Scholar
  10. 10.
    Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323: 1505–11CrossRefGoogle Scholar
  11. 11.
    Connolly SJ, Laupacis A, Gent M, et al. Canadian atrial fibrillation anticoagulation (CAFA) study. J Am Coll Cardiol 1991; 18: 349–55CrossRefPubMedGoogle Scholar
  12. 12.
    Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. N Engl J Med 1992; 327: 1406–12CrossRefPubMedGoogle Scholar
  13. 13.
    Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. Lancet 1989; I: 175–9CrossRefGoogle Scholar
  14. 14.
    Stroke Prevention in Atrial Fibrillation Study Group Investigators. Stroke prevention in atrial fibrillation study: final results. Circulation 1991; 84: 527–39CrossRefGoogle Scholar
  15. 15.
    McCrory DC, Matchar DB, Samsa G, et al. Physician attitudes about anticoagulation for nonvalvular atrial fibrillation. Arch Intern Med 1995; 155: 277–81CrossRefPubMedGoogle Scholar
  16. 16.
    Kutner M, Nixon G, Silverstone F. Physicians’ attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation. Arch Intern Med 1991; 151: 1950–3CrossRefPubMedGoogle Scholar
  17. 17.
    Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 1995; 155: 469–73CrossRefPubMedGoogle Scholar
  18. 18.
    Antani MR, Beyth RJ, Covinsky KE, et al. Failure to prescribe warfarin to patients with nonrheumatic atrial fibrillation. J Gen Intern Med 1996; 11: 713–20CrossRefPubMedGoogle Scholar
  19. 19.
    Beyth RJ, Antani MR, Covinsky KE, et al. Why isn’t warfarin prescribed to patients with nonrheumatic atrial fibrillation? J Gen Intern Med 1996; 11: 721–8CrossRefPubMedGoogle Scholar
  20. 20.
    Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956–66PubMedGoogle Scholar
  21. 21.
    Bergman HD, Aoki VS, Black HJ, et al. A new role for the pharmacist in the detection and evaluation of adverse drug reactions. Am J Hosp Pharm 1971; 28: 343–50PubMedGoogle Scholar
  22. 22.
    Hurwitz N. Predisposing factors in adverse reactions to drugs. BMJ 1969; 1:536–9CrossRefPubMedGoogle Scholar
  23. 23.
    Klein U, Klein M, Sturm H, et al. The frequency of adverse drug reactions as dependent upon age, sex, and duration of hospitalization. Int J Clin Pharmacol Biopharm 1976; 13: 187–95PubMedGoogle Scholar
  24. 24.
    Levy M, Kletter-Hemo D, Nir I, et al. Drug utilization and adverse drug reactions in medical patients: comparison of two periods. Isr J Med Sci 1977; 13: 1065–71PubMedGoogle Scholar
  25. 25.
    Olgilvie RI, Ruedy J. Adverse drug reactions during hospitalization. Can Med Assoc J 1967; 97: 1450–7Google Scholar
  26. 26.
    Seidl LG, Thornton GF, Smith JW, et al. Studies on the epidemiology of adverse drug reactions; III. reactions in patients on a general medical service. Bull John Hopkins Hosp 1966; 119: 299–315Google Scholar
  27. 27.
    Smidt NA, McQueen EG. Adverse reactions to drugs: a comprehensive hospital inpatient survey. N Z Med J 1972; 76: 397–401PubMedGoogle Scholar
  28. 28.
    Hutchinson TA, Flegel KM, Kramer MS, et al. Frequency, severity and risk factors for adverse drug reactions in adult outpatients: a prospective study. J Chronic Dis 1986; 39: 533–42CrossRefPubMedGoogle Scholar
  29. 29.
    Kellaway GS, McCrae E. Intensive monitoring for adverse drug effects in patients discharged from acute medical wards. N Z Med J 1973; 78: 525–8PubMedGoogle Scholar
  30. 30.
    Smith JW, Seidl LG, Cluff LE. Studies on the epidemiology of adverse drug reactions; V. clinical factors influencing susceptibility. Ann Intern Med 1966; 65: 629–40PubMedGoogle Scholar
  31. 31.
    Williamson J, Chopin JM. Adverse reactions to prescribed drugs in the elderly: a multicenter investigation. Age Ageing 1980; 9: 73–80CrossRefPubMedGoogle Scholar
  32. 32.
    Grymonpre RE, Mitenko PA, Sitar DS, et al. Drug-associated hospital admissions in older medical patients. J Am Geriatr Soc 1988; 36: 1092–8PubMedGoogle Scholar
  33. 33.
    Gurwitz JH, Avorn J, Ross-Degnan D, et al. Aging and the anticoagulant response to warfarin therapy. Ann Intern Med 1992; 116: 901–4PubMedGoogle Scholar
  34. 34.
    Nolan L, O’Malley K. Prescribing for the elderly: part II. prescribing patterns: difference due to age. J Am Geriatr Soc 1988; 36: 245–54PubMedGoogle Scholar
  35. 35.
    Guralnik JM, LaCroix AZ, Everett DF, et al. Aging in the eighties: the prevalence of comorbidity and association with disability. In: Anonymous. Advance data from vital and health statistics, no. 170. Hyattsville (MD): National Center for Health Statistics, 1989Google Scholar
  36. 36.
    Seeman TE, Guralnik J, Kaplan GA, et al. The health consequences of multiple morbidity in the elderly: the Alameda County study. J Aging Health 1989; 1: 50–66CrossRefPubMedGoogle Scholar
  37. 37.
    US Senate Special Committee on Aging (1987-88). Aging America, 1988: trends and projections. Washington, DC: US Department of Health and Human Services, 1991Google Scholar
  38. 38.
    Toohey M. Clinical trial of phenylindanedione as an anticoagulant. BMJ 1953; 1: 650–62CrossRefPubMedGoogle Scholar
  39. 39.
    O’Malley K, Stevenson IH, Ward CA, et al. Determinants of anticoagulant control in patients receiving warfarin. Br J Clin Pharmacol 1977; 4: 309–14CrossRefPubMedGoogle Scholar
  40. 40.
    Shepherd AMM, Hewick DS, Moreland TA, et al. Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol 1977; 4: 315–20CrossRefPubMedGoogle Scholar
  41. 41.
    Friedman SA. Organ systems: cardiovascular disorders. In: Abrams WB, Berkow R (editors). The merck manual of geriatrics. Rahway (NJ): Merck Sharp and Dohme Research Laboratories, 1990: 408Google Scholar
  42. 42.
    Masuda J, Tanak K, Ueda K, et al. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. Stroke 1988; 19: 205–10CrossRefPubMedGoogle Scholar
  43. 43.
    Vonsattel JP, Myers RH, Hedley-Whyte ET, et al. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991; 30: 637–49CrossRefPubMedGoogle Scholar
  44. 44.
    Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897–902PubMedGoogle Scholar
  45. 45.
    Beyth RJ, Landefeld CS. Anticoagulants in older patients: a safety perspective. Drugs and Aging 1995; 6: 45–54CrossRefPubMedGoogle Scholar
  46. 46.
    Stroke Prevention in Atrial Fibrillation Study Group Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: stroke prevention in atrial fibrillation II study. Lancet 1994; 343: 687–91Google Scholar
  47. 47.
    Fihn SD, Callahan CM, Martin DC, et al. The risk and severity of bleeding complications in elderly patients treated with warfarin. Ann Intern Med 1996; 124: 970–9PubMedGoogle Scholar
  48. 48.
    Beyth RJ, Landefeld CS. Are older patients at increased risk for major bleeding during anticoagulant therapy? [abstract]. Clin Res 1992; 40: 552AGoogle Scholar
  49. 49.
    Fihn SD, McDonell M, Martin D, et al. Risk factors for complications of chronic anticoagulation: a multicenter study. Ann Intern Med 1993; 118: 511–20PubMedGoogle Scholar
  50. 50.
    Gurwitz JH, Goldberg RJ, Holden A, et al. Risk factors for complications of chronic anticoagulation: a multicenter study. Arch Intern Med 1988; 148: 1733–6CrossRefPubMedGoogle Scholar
  51. 51.
    Diabetes Control and Complications Trial Research Group. Hypoglycemia in the diabetes control and complications trial. Diabetes 1997; 46: 271–86CrossRefGoogle Scholar
  52. 52.
    Gold AE, Frier BM, MacLeod KM, et al. A structural equation model for predictors of severe hypoglycemia in patients with insulin-dependent diabetes mellitus. Diabet Med 1997; 14: 309–15CrossRefPubMedGoogle Scholar
  53. 53.
    Cox DJ, Kovatchev BP, Julian DM, et al. Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring blood glucose data. J Clin Endocrinol Metab 1994; 79: 1659–62CrossRefPubMedGoogle Scholar
  54. 54.
    Harris MI. Epidemiology of diabetes mellitus among the elderly in the United States. Clin Geriatr Med 1990; 6: 703–19PubMedGoogle Scholar
  55. 55.
    Leibson CL, O’Brien PC, Atkinson E, et al. Relative contributions of incidence and survival to increasing prevalence of adult-onset diabetes mellitus: a population-based study. Am J Epidemiol 1997; 146: 12–22CrossRefPubMedGoogle Scholar
  56. 56.
    Kenny SJ, Aubert RE, Geiss LS. Prevalence and incidence of non-insulin-dependent diabetes. In: National Diabetes Data Group (editors). Diabetes in America. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health; 1995, 47–68. Publication no. NIDDK-NIH- 95-1468Google Scholar
  57. 57.
    Cowie CC, Port FK, Wolfe RA, et al. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med 1989; 321: 1074–9CrossRefPubMedGoogle Scholar
  58. 58.
    Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–97Google Scholar
  59. 59.
    American Diabetes Association. Standards of medical care for patients with diabetes. Diabetes Care 1997; 20: S5–13Google Scholar
  60. 60.
    Turner R, Cull C, Holman R. United Kingdom prospective diabetes study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med 1996; 124: 136–45PubMedGoogle Scholar
  61. 61.
    Shorr RI, Ray WA, Daugherty JR, et al. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc 1996; 44: 751–5PubMedGoogle Scholar
  62. 62.
    Shorr RI, Ray WA, Daugherty JR, et al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157: 1681–6CrossRefPubMedGoogle Scholar
  63. 63.
    Shorr RI, Ray WA, Daugherty JR, et al. Antihypertensives and the risk of serious hypoclycemia in older persons using insulin or sulfonylureas. JAMA 1997; 278: 40–3CrossRefPubMedGoogle Scholar
  64. 64.
    Roth SH. Salicylates revisited: are they still the hallmark of anti-inflammatory therapy? Drugs 1988; 36: 1–6CrossRefPubMedGoogle Scholar
  65. 65.
    Gurwitz JH, Avorn J, Ross-Degnan D, et al. Nonsteroidal antiinflammatory drug-associated azotemia in the very old. JAMA 1990; 264: 471–5CrossRefPubMedGoogle Scholar
  66. 66.
    Roth SH. Nonsteroidal anti-inflammatory drug gastropathy: we started it — can we stop it? Arch Intern Med 1986; 146: 1075–6CrossRefPubMedGoogle Scholar
  67. 67.
    Roth SH, Bennett RE, Mitchell CS, et al. Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy: double-blind long-term evaluation. Arch Intern Med 1987; 147: 1798–801CrossRefPubMedGoogle Scholar
  68. 68.
    Armstrong CP, Blower AL. Nonsteroidal anti-inflammatory drugs and life-threatening complications of peptic ulceration. Gut 1987; 28: 527–32CrossRefPubMedGoogle Scholar
  69. 69.
    Fries JF, Miller SR, Spitz PW, et al. Toward an epidemiology of gastropathy associated with nonsteroidal anti-inflammatory drug use. Gastroenterology 1989; 96: 647–55PubMedGoogle Scholar
  70. 70.
    Collier DS, Pain JA. Nonsteroidal anti-inflammatory drugs and peptic ulcer perforation. Gut 1985; 26: 359–63CrossRefPubMedGoogle Scholar
  71. 71.
    Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 1988; 109: 359–63PubMedGoogle Scholar
  72. 72.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115:787–96PubMedGoogle Scholar
  73. 73.
    Guess HA, West R, Strand LM, et al. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada. J Clin Epidemiol 1988; 41: 35–45CrossRefPubMedGoogle Scholar
  74. 74.
    Griffin MR, Piper JM, Daugherty JR, et al. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991; 114: 257–63PubMedGoogle Scholar
  75. 75.
    Langman MJS, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075–8CrossRefPubMedGoogle Scholar
  76. 76.
    Smalley WE, Griffin MR, Fought RL, et al. Effect of a prior-authorization requirement on the use of nonsteroidal anti-inflammatory drugs by Medicaid patients. N Engl J Med 1995; 332: 1612–7CrossRefPubMedGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Division of General Internal Medicine and Healthcare Research, Cleveland Veterans Affairs Medical CenterUniversity Hospitals of Cleveland and Case Western Reserve UniversityClevelandUSA
  2. 2.Department of Preventative Medicine, College of MedicineUniversity of Tennessee and the Methodist Hospital of MemphisMemphisUSA
  3. 3.Division of General Internal Medicine and Healthcare ResearchCase Western Reserve University, School of MedicineClevelandUSA

Personalised recommendations