The Ambiguous Relation between Aging and Adverse Drug Reactions

PURPOSE: To examine the evidence for a relation between advancing patient age and the risk for adverse drug reactions. DATA SOURCE: A computer-assisted search of the English-language literature (MEDLINE, 1966 to 1990) followed by selective review of all pertinent articles. STUDY SELECTION: Studies that stratified data on adverse drug reactions by patient age were screened for review. Article selection was not limited by study design; the relation between age and the occurrence of adverse drug reactions did not have to be a primary focus of the study. DATA EXTRACTION: Pertinent data were abstracted from the results of case-control and cohort studies and from clinical trials. The methodologic strengths and weaknesses of these studies are discussed with particular reference to gerontologic issues. RESULTS OF DATA SYNTHESIS: Most studies have neglected the issue of whether the increased frequency of adverse drug reactions in the elderly is attributable to age alone or to the fact that older patients are more likely to have coexisting illnesses and to be taking several medications. Studies that combine all drug exposures for each patient and report the risk for any adverse effect provide little useful information about the risks associated with specific drug therapies in the elderly. The association between age and the risk for adverse drug reactions is best examined for individual pharmacologic agents. However, the exclusion of elderly subjects from clinical trials makes the determination of age effects impossible in many studies. Where subjects do represent an adequate age range, most studies fail to control for important clinical differences among subjects of different ages to distinguish the independent effects of chronologic age. CONCLUSION: Conventional clinical wisdom suggests that the risk for adverse drug reactions increases with advancing age, but available data do not confirm this "truism" of geriatric medicine. The inter-individual variability of the aging process, including the non-uniform nature of the pharmacokinetic and pharmacodynamic changes that occur with aging, indicates that clinical reality is far more complex. Patient-specific physiologic and functional characteristics are probably more important than any chronologic measure in predicting both adverse and beneficial outcomes associated with specific drug therapies.