By Robert L. Kass, MD
Many studies have shown the benefits of certain medications for improving long-term outcomes in patients with chronic conditions. However, even when evidence-based recommendations are closely followed, there is a potential for adverse consequences because of the concurrent use of multiple medications. Such consequences include the following (Maher et al., 2014):
- Increased likelihood of an adverse event due to a single drug
- Harmful interactions between drugs
- Increased healthcare costs
- Nonadherence to medication regimens
- Functional decline
- Cognitive impairment
- Urinary incontinence
As the population has aged and mortality rates have declined, these adverse consequences are challenging to clinicians treating older adults in particular, because of the increased prevalence of multimorbidity (i.e., the coexistence of two or more chronic health conditions) (Salive, 2013). Older patients are also more vulnerable to the adverse effects of medications because of age-associated physiological changes, including decreased renal and hepatic function, decreased lean body mass and total body water content, and declining vision and hearing (Bushardt et al., 2008).
Assessing the appropriateness of polypharmacy
The use of multiple medications is often referred to as polypharmacy in the medical literature, but there is no standard definition for this term. A great majority of clinical articles define polypharmacy based on the number of medications used, with the most common definition being the use of five or more medications daily (Masnoon et al., 2017). It is more useful, however, to look carefully at the appropriateness of the medications prescribed rather than merely the number of medications. While some investigators have noted that the lack of a clear, universal definition of polypharmacy creates difficulties for assessing safety and efficacy issues within a clinical setting, others have recommended using a less ambiguous term such as hyperpharmacotherapy to specify pharmacotherapy that is indeed inappropriate for a particular patient (Bushardt et al., 2008).
There are many reasons a particular medication may be inappropriate for a patient:
- The medication is prescribed to treat side effects due to another medication. This has been called a prescribing cascade (Liacos et al., 2020), and it results in a patient receiving multiple medications with both increased risk and cost, when it would have been better to reassess the use of the original medication responsible for the side effects.
- There is therapeutic duplication—that is, similar medications are used simultaneously to treat the same symptom (Hajjar et al., 2005).
- Drug-drug interactions. The probability of cytochrome P450–mediated interactions between drugs, in which one drug affects the metabolism of another, has been reported to be 50% in patients age 65 and older who are taking five to nine medications (Doan et al., 2013). Note that interactions may also occur between prescription medications and over-the-counter medications and herbal supplements (Bushardt et al., 2008).
- The medication is no longer necessary, such as:
- A medication that was once needed to treat a symptom that has since resolved (Liacos et al., 2020)
- Preventive medications used beyond the time frame that evidence has shown them to be beneficial (e.g., prolonged dual-antiplatelet therapy beyond the recommended duration after percutaneous coronary intervention) (Liacos et al., 2020)
- Combination therapy used when one medication might suffice (e.g., the OPTIMISE randomized controlled trial showed that in patients age 80 and older taking at least two antihypertensive medications, the removal of one drug is noninferior to usual care for short-term blood pressure control) (Sheppard et al., 2020)
- The medication is potentially inappropriate for elderly patients. The American Geriatric Association has published the Beers Criteria® for Potentially Inappropriate Use in Older Adults, which are updated every three years. These criteria list medications that are best avoided in all older adults under most circumstances as well as those best avoided under specific situations, such as in older adults who have certain diseases or conditions (American Geriatrics Society, 2019).
Even if clinical practice guidelines are strictly followed, problems with medication interactions will often remain. Many published guidelines do not take into account the multiple chronic conditions commonly found in older patients. A hypothetical 79-year-old woman with Type 2 diabetes, hypertension, chronic obstructive pulmonary disease, osteoporosis, and osteoarthritis might be prescribed 12 medications daily if all recommendations from the relevant guidelines were implemented (Boyd et al., 2005).
What can clinicians do?
Being mindful of these concepts is the first step in safer prescribing, but there are also tools that can assist a clinician who is considering prescribing a new medication:
- Medical Appropriateness Index (Hanlon & Schmader, 2013)
- Beers Criteria (American Geriatrics Society, 2019)
- STOPP/START criteria (O’Mahony et al., 2018)
Deprescribing—that is, discontinuing medications that may be unnecessary or potentially harmful—is another important strategy. Randomized studies have shown significant reductions in mortality with patient-specific interventions for deprescribing (Page et al., 2016).
Although it is prudent to review and reevaluate a patient’s medications as frequently as possible, there are certain indicators that should prompt a clinician to prioritize doing so for a particular patient (Liacos et al., 2020):
- A recent fall
- Hospital admission
- Admission to a residential care facility
- Increasing frailty
- Decline in cognitive function
- Decline in ability to manage activities of daily living
Tools that can help clinicians with deprescribing decisions include published algorithms, flowcharts, and tables designed to guide them through sequential decisions about which medications might be safely discontinued for a specific patient (Scott et al., 2017).
There are barriers to deprescribing that should be considered, often due to patient or caregiver belief that a drug is still necessary or due to fear of withdrawal. These barriers can be overcome by taking the time to educate the patient or caregiver on the risks and benefits of medication use, clearly discussing a plan for monitoring the patient after a medication is discontinued, and providing clear instructions on drug tapering, if required. It is also helpful to provide reassurance that the medication may be restarted if necessary (Liacos et al., 2020).
Ideally, clinicians should work with their patients to keep comprehensive, portable medication lists, including over-the-counter and alternative therapies; these lists should note the indication for each drug, the symptoms and signs each drug is meant to address, and how to monitor for efficacy and adverse effects (Steinman, 2016).
Robert Kass, MD, is a managing editor with Zynx Health Incorporated.
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Sheppard, J. P., Burt, J., Lown, M., Temple, E., Lowe, R., Fraser, R., Allen, J., Ford, G. A., Heneghan, C., Hobbs, F. D. R., Jowett, S., Kodabuckus, S., Little, P., Mant, J., Mollison, J., Payne, R. A., Williams, M., Yu, L-M., & McManus, R. J. (2020). Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: The OPTIMISE randomized clinical trial. JAMA, 323(20), 2039–2051. https://doi.org/10.1001/jama.2020.4871
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