Abstract
Older adults are prescribed a growing number of medications. Polypharmacy, commonly considered the receipt of five or more medications, is associated with a range of adverse outcomes. There is a debate about the reason(s) why. On one side is the assertion that older persons are being prescribed too many medications, with the number of medications increasing the risk of adverse events. On the other side is the observation that polypharmacy is associated both with overprescribing of inappropriate medications and underprescribing of appropriate medications. This leads to the concept of "inappropriate" vs "appropriate" polypharmacy, with the latter resulting from the prescription of many correct medications to persons with multiple chronic conditions. Few studies have examined the health outcomes associated with adding and/or removing medications to address this debate directly. The criteria used to identify underutilized medications are based on results of randomized controlled trials that may not be generalizable to older adults. Several randomized controlled trials and many more observational studies provide evidence that these criteria overestimate medication benefits and underestimate harms. In addition, evidence suggests that the marginal effects of medications added to an already complex regimen differ from their effects when considered individually. Although in selected circumstances adding medications results in benefit to patients, patients with multimorbidity and frailty/disability have susceptibilities that can decrease the likelihood of medication benefit and increase the likelihood of harms. The identification of appropriate polypharmacy requires more robust criteria to evaluate the net effects of complex medication regimens.