Multiple chronic conditions and the taking of many prescription medications to treat them — polypharmacy* — are common among the elderly. Two-thirds of Medicare beneficiaries have two or more chronic conditions, and almost half take five or more medications. Because drugs can interact with one-another and the drug to treat one condition can exacerbate another, polypharmacy raises health and safety concerns.

Indeed, studies have found an association of polypharmacy with adverse outcomes. It's eminently reasonable that polypharmacy is predictive of adverse outcomes because those prescribed more medications tend to be sicker. An important question is, to what extent does polypharmacy cause bad outcomes? And, if it's causal, what can be done?

A systematic review of research literature through mid-2014 is somewhat informative on these matters, though perhaps not as informative as we might like. It found 58 articles relevant to the question,

In community living persons aged 65 and older receiving outpatient care, what are the clinical outcomes associated with polypharmacy related to medications taken for chronic conditions?

Importantly, all of the studies are observationalMany clinical trials explicitly exclude older patients, who are more likely to have multiple comorbidities requiring many drugs. Randomizing patients to take more drugs is, for good reason, not likely to get the blessing of an institutional review board. So we don't know as much about polypharmacy from randomized trials as we might like. In summary, the review found that:

  • Fall-related outcomes (like dizziness or fracture, if not falls itself) were among the most frequently examined (23 studies). Among the 14 studies with good adjustments for comorbidities, according to the reviewers, 12 found at least one positive association between polypharmacy and a fall-related outcome.
  • Adverse drug events (ADEs) — variously defined — were examined in 14 studies. Among the eight judged as having good adjustment for comorbidities, five found an association between polypharmacy and ADEs.
  • Ten studies examined hospitalization or mortality. Of these, only four were judged to have good controls for comorbidities. Three of those found an association between polypharmacy and all-cause hospitalization or mortality. The fourth found one for influenza-related hospitalization and mortality.
  • Fifteen studies focused on a variety of other outcomes from general health to specific cognitive or physical symptoms or function, ten of which were judged as having good controls for comorbidities. All ten found at least one association between polypharmacy and a bad outcome.

Despite these findings, it's still not evident that polypharmacy causes bad outcomes. Sicker people take more drugs and, no surprise, experience bad health events because they are sick. Even if controls for comorbidities are "good," they don't capture all aspects of health conditions that lead to medications and relate to outcomes. Moreover, its not likely the case that the number of drugs, per se, causes bad outcomes but that the taking of specific drugs or specific drugs in combination does so.

As the authors put it,

[T]he number of medications [may be] a marker for the use of individual medications with a well established risk of causing adverse events, such as psychotropic agents and other medications that expert consensus has established as inappropriate for some or all older persons.

Interventions to reduce inappropriate prescribing can improve outcomes. One randomized trial found that clinical pharmacist evaluation of drug regimens for patients taking five or more medications on a routine basis reduced adverse drug events from 40% to 30% (not statistically significant). Another randomized trial found that geriatric evaluation and management reduced unnecessary/inappropriate drug use and reduced adverse drug reactions by 35%. Relative to a control group, falls were reduced among a group of elderly, community-dwelling patients through a program that included a review of medications and, on average, reduced medication use.

From this literature, it is clear that polypharmacy is at least an indicator of greater likelihood of unnecessary, inappropriate, or conflicting medications. Careful review of them can eliminate drugs or change dosing to reduce the chance of adverse events.

* Though I'm using "polypharmacy" to mean the use of multiple medications, others define it as the use of medications not clinically indicated (inappropriate use).

Austin Frakt
Author, Committee Member, Member

Austin Frakt, Ph.D.

The Incidental Economist Chair, Translation and Dissemination Institute Advisory Committee

Austin is a health economist and researcher; the creator, co-manager, and a primary author of The Incidental E... Read Bio