Polypharmacy is defined as the concurrent use of multiple medications by a patient. Polypharmacy has become a ubiquitous term; unfortunately, the definition of the term is less well known. A 2017 systemic review of 110 articles defining the term demonstrated 138 different definitions for the term. Most of those definitions of polypharmacy were based on the number of medications the patient is taking, ranging from 2 to 11. On average, the most used definition of polypharmacy was related to a medication count greater than or equal to 5.1 In 2020, a separate systemic review noted similar variety in the definition of polypharmacy. As before, greater than 50% of the definitions used five or more medications as the defining criteria.2
In recent decades in healthcare, there has been a shift to provide evidenced-based practices to patients in our care. This shift has created a culture of guideline-driven medicine leading to many disease drug processes being treated by multidrug regimens, with the goal being to obtain maximum results for that patient by encouraging standardized care. Additionally, the fact that a financial incentive has been tied to performance has only increased the extensive use of guideline-driven medical practices.
No one doubts the use of certain drug regimens such as the use of beta-blockers in preventing recurrent myocardial infarctions or the use of statins to reduce the risk of cardiovascular events and mortality in patients with and without known cardiovascular disease. However, the full ramifications of these multidrug regimens in patients with multiple comorbid conditions, in the long run, are not fully understood.
According to the Centers for Medicaid and Medicare Services, during the years 2007 to 2014, about 13% of their members registered for Medicare fee-for-service programs had more than five chronic conditions. 22% of patients had 4 to 5 chronic conditions. This data establishes that more than a third of all registered participants had greater than three chronic conditions. The Slone survey showed that over 50 percent of Medicare beneficiaries reported receiving five or more medications.3
In a recent study among ambulatory older adults with cancer, 84 percent were reported to receive five or more, and 43 percent were receiving ten or more medications.4 With the increasing life expectancy in the United States, clinicians must take care of more and more patients with chronic conditions. Furthermore, this becomes even more challenging when a single patient has several chronic conditions.
It is well established that the issue surrounding polypharmacy affects older people more compared to younger age groups, which is expected given that they have more disease conditions. Also, the fact that life expectancy continues to increase implies that this is a condition that we will have to deal with on a more frequent basis.
Older patients are most susceptible to side effects of polypharmacy for multiple reasons, such as a greater risk for adverse drug events due to decreased drug clearance by the hepatic and renal systems associated with aging. Note that the increased number of drugs compounds the risk.
Polypharmacy increases the risk for potential drug-drug interactions and the risk of sustaining a hip fracture, especially specific drugs associated with falls such as the central nervous system active drugs. Overall older adults have trouble with medication adherence, which is exacerbated by cognitive and visual limitations.
It is not clear what the benefits and harm associated with the combination of all these multidrug regimens. While most people tout the adherence to disease-specific guidelines, there is very little information about the risk associated with merging multiple disease-specific drug regimens. In their study examining the potential pitfalls of disease-specific guidelines for patients with multiple conditions, Tinneti et al, elaborated on an example of a 70-year-old woman who has a common combination of hypertension, myocardial infarction, depression, diabetes mellitus, and osteoporosis. Based on the adherence to disease guidelines, the patient may be required to take aspirin, an ACE inhibitor, a beta-blocker, a bisphosphonate, calcium, a diuretic, a selective serotonin-reuptake inhibitor, a statin, a sulfonylurea drug, perhaps a thiazolidinedione, and vitamin D. Furthermore, these medications do not include the treatment of common conditions such pain and heartburn which are commonly treated with over-the-counter medications. When viewed in this perspective, it raises the question of whether what is good for the disease is always best for the patient.5
Polypharmacy has been shown to increase the risk of adverse drug reactions, drug interactions, cognitive impairment, and medication inappropriateness6, Overall, leading to increased healthcare utilization, which may present as increased outpatient visits related to adverse drug interactions or increased risk of hospitalization. The likelihood of hospitalizations is 34% in patients taking between 5 to 9 medications. In patients taking ten or more medications, the likelihood of hospitalizations increases to 98%.
The occurrence of drug-drug interactions increases as the number of medications increases. The rate of drug-drug interactions in patients taking 5 to 9 medications was reported as 50%, and it increases to 100% in patients taking 20 or more medications.7 Each additional medication may increase the risk of potential interactions by about 12%.
When addressing polypharmacy, we usually think about prescription medication. However, we must consider the number of over-the-counter drugs and herbal supplements that patients use.