≥ 92% of participants will understand how polypharmacy affects patient populations, specifically the elderly population, and how it relates to adverse drug reactions and potentially inappropriate medications. Finally, the learner will know the role that clinicians play in mitigating the effects of polypharmacy and the clinical tools at their disposal.
After completing this course, the learner will be able to:
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.
There is a symbiotic relationship between adverse drug reactions and polypharmacy, with each causing or occurring because of the other. The World Health Organization (WHO) defines adverse drug effects as "noxious and unintended responses to drugs occurring at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or modification of physiological function.8"
Adverse drug reactions are classified into six different subtypes which are:
Adverse drug events and adverse drug reactions are often used erroneously as interchangeable terms. However, adverse drug events is a more comprehensive term which comprises adverse drug reactions and as well as reactions secondary to medical error. Adverse Drug Reactions (ADR) have significant ramifications on health, with an estimated 5% to 7% of all hospitalizations occurring secondary to an ADR. Also, 10% to 20% of all hospitalized patients will experience an adverse drug reaction during their hospital stay. In the United States, it has been estimated that up to 6% of ADRs have fatal or severe consequences, thereby increasing morbidity and mortality from adverse reactions. Approximately 140,000 fatalities caused by ADRs are reported to occur in the United States each year. The financial impact on hospitals has been reported to exceed $30 billion and approximately 5% of the annual hospital running costs.9 Using an increased number of drugs has also been independently linked to increased risk for hospital admissions. One study has estimated the average annual cost of drug-related morbidity and mortality at $76.6 million for out of hospital patients.
Pont et al. conducted a systematic review and reported that the mean prevalence of ADRs leading to hospitalization was 11%, while the prevalence of ADRs occurring during hospitalization was 11%.9 Their review concluded that one in ten older patients would experience an adverse drug reaction, either leading to a hospital stay or during a hospital stay. Also, older patients with increased disease burden and using multiple drugs were at increased risk of an adverse drug reaction. They also identified the need for a more accurate definition of what should be considered an adverse drug reaction in future research endeavors.
Recent studies have shown that elderly patients vary with the importance they place on health outcomes such as longer survival, the prevention of specific disease events as well as the risk that they are willing to take in in terms of the adverse events they are willing to tolerate.
Clinicians understand that when prescribing medications to a patient, the plan must be individualized, with the patient's overall health considered. However, the challenge that clinicians face is that one of the hallmarks of quality assurance programs concerning disease-specific guidelines is a reduction in the variation of practice patterns among providers. It is difficult to distinguish between appropriate and inappropriate variation in practice patterns among providers. Thus, there is constant discord between the standardized treatment of diseases and the individualized care of patients. It is almost impossible to provide individualized care when measured by quality assurance programs that recommend standardized treatments.
To further expand on this disconnect, it is critical to realize that while clinicians focus on disease-specific outcomes such as maintenance of disease-free intervals as well as the prevention of specific outcomes such as pulmonary emboli, a patient is more concerned about the specific factors such as; side effects of medications, time to take effect, the convenience of medication regimen and the cost associated with the prescribed regimen. In a nutshell, clinicians may be focused on the disease process while a patient is more focused on their current quality of life and how it is affected by a medication regimen.
A study published by Kalogianis et al., 2015 showed that up to 40.5% of residents in residential aged care facilities reported a desire to stop taking one or more medications. Almost 80% of residents (78.8%) were willing to discontinue one or more of their medications. The study focused on examining if residents were willing to have medications deprescribed because, after all, the point is moot if residents are not willing to participate in deprescribing interventions. Specifically, residents taking nine or more medications were more likely to believe that their medications were causing side effects.10
We must understand that patients with multiple conditions present unique challenges in terms of disease diagnosis and management. Another factor that potentiates polypharmacy is that patients with chronic conditions are usually treated by multiple specialists who do not always communicate with each other.
Some general principles that can be used to mitigate the effects of polypharmacy in the elderly include:
According to the American Cancer Society, it is estimated that by the year 2030, 70% of all cancers in the United States will be diagnosed in the elderly population. The challenge faced in this group's management is the multiple layers of professionals involved in caring for this group, such as geriatricians, oncologists, radiologists, pharmacists, allied health professionals such as nurses, speech therapists, occupational therapists, and social workers. Most medication errors are attributed to medication changes, complex regimens, and inadequate communications between providers caring for a specific patient. Polypharmacy increases the vulnerability of the older population because it increases the risk of falls, fractures, cognitive impairment, and delirium, all of which affect morbidity in this population.11
Increased pill burden has been described to increase the risk of drug-drug, drug-food, and drug-herbal interactions.
Any comprehensive medication assessment guideline should include the following:
The problem with all these recommendations is that they do not specify which health care professional should be responsible for performing the medication assessment. Often this duty has been relegated to primary care providers. Sometimes, the challenge is that a patient sees other specialized providers more frequently than they see their primary care providers.
The following case study published by Rosenberg et al., 2014 in the journal of the American Geriatrics Society exemplifies the challenge faced with addressing the implications and consequences of polypharmacy.12
The patient is a 70-year-old with a subdural and bilateral frontal lobe contusions after sustaining an unwitnessed fall in his home. Upon admission, he was noted to have an elevated salicylate level. An abdominal x-ray done on admission showed some radiopaque materials in his colon, even though he had not received any contrast material. Since no collateral history was available, the assumption was made that the salicylic acid toxicity was secondary to a medication error. His pharmacy was able to confirm that he had not purchased any acetylsalicylic acid either prescribed or over the counter. His medications included: Donepezil, calcium carbonate, alendronate, pravastatin, ezetimibe, omeprazole, and perindopril, with no history of medication overdose. All these medications were long-standing, except Donepezil, which is a cholinesterase inhibitor. Upon further review, it was noted that the patient was diagnosed with mild Alzheimer's disease two months earlier. Shortly after initiating Donepezil, he visited his family physician complaining of persistent abdominal discomfort and diarrhea, for which he was referred to a gastroenterologist.
A close friend eventually revealed that he had self-medicated with large amounts of bismuth subsalicylate (Pepto-Bismol®) because it provided some temporary relief of his abdominal discomfort. Pepto-Bismol® contains 8.7 mg of salicylic acid per mL and can cause both acute and chronic salicylate toxicity when consumed excessively.
The friend specifically recalled that the patient's cognitive status had acutely and progressively worsened after Pepto-Bismol® was initiated. His gait and functional impairment concurrently deteriorated and culminated in the traumatic fall. Bismuth is also slightly radiopaque, explaining the contrast material visualized throughout the colon on the pelvic X-ray.
This case involves three relevant medication issues: a prescribing cascade, salicylate toxicity, and bismuth neurotoxicity.
The salicylate toxicity and subsequent traumatic fall were probably secondary to self-medication with OTC bismuth subsalicylate for the relief of gastrointestinal symptoms temporally related to the initiation of a cholinesterase inhibitor. This pattern represents a prescribing cascade, in which an adverse drug reaction to a medication is misinterpreted as a new medical condition, leading to another drug being prescribed to treat the adverse effect. Both the patient and his physician misinterpreted the adverse gastrointestinal effects of the cholinesterase inhibitor as a new medical condition, leading to self-medicating with an additional over-the-counter drug at toxic doses.
Gastrointestinal symptoms are a known side effect of Donepezil, and side effects usually experienced include abdominal pain, nausea, anorexia, diarrhea, and weight loss. Given that many older adults with dementia are malnourished, providers prescribing cholinesterase inhibitors must inform them about these potential adverse events.
The neurotoxicity caused by bismuth subsalicylate is usually not diagnosed despite its long history of use for multiple gastrointestinal disorders. Two distinct toxicities must be considered: salicylate toxicity and bismuth toxicity. Salicylate toxicity is described in the above case study. Bismuth neurotoxicity can provoke delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks when bismuth intake is stopped.
In conclusion, this case highlights the potential for prescribing cascades involving OTC preparations that are sometimes missed when taking a medication history. The nutshell of the matter is that there is always a possibility that an adverse drug event could be masquerading as a prescribing cascade. Thus, the possibility of a prescribing cascade should always be carefully considered when evaluating an older adult, and any new symptom should be drug-related until proven otherwise.
Prescribing cascades are described as scenarios occurring when a new drug is prescribed to treat symptoms arising from an unrecognized side effect of a drug the patient is already taking. Older adults are particularly susceptible to prescribing cascades, which develop when an adverse drug event is misinterpreted as a new medical condition. Additional drug therapy is subsequently prescribed to treat this medical condition. Prescribing cascades are particularly common when drug-induced symptoms are indistinguishable from illnesses that are common in older persons.
A commonly identified prescribing cascade is the initiation of anti-Parkinson therapy for symptoms arising from the use of drugs such as antipsychotics or metoclopramide. These new anti-Parkinson drugs, in turn, cause new symptoms, including orthostatic hypotension and delirium, which may or may not be treated by the prescription of new drugs. Another study that further underscores the risk for prescribing cascade is the study published by Silva et al., 2016 provided a summary of cases that showed that 41 cases of acute pancreatitis were associated with antipsychotics and over 53% of the cases associated with polypharmacy.13
As an alternative to the knee jerk reaction to prescribing medications leading to prescribing cascades, the following alternatives have been proposed; carefully reevaluating the absolute need for the offending agent, using non-pharmacological interventions for managing the patient's side effects, lowering the dose of the implicated drug to the lowest possible dose feasible for treating the patient's condition and finally considering other drugs with a better side effect profile.
The risk of polypharmacy underscores the continued need to review widely adopted medication guidelines for common disease processes, especially diseases affecting elderly patients.
A 75-year-old man comes into a primary care clinic where you are working as a nurse manager in charge of managing the onboarding process for new patients. He is coming to establish care and has the following diagnoses: hypertension, heart failure, diabetes mellitus type 2, and chronic kidney disease - stage 2 and metastatic prostate cancer. He is currently taking the following medications: Aspirin, Metoprolol, Thiazide diuretic, Lasix, Metformin, Oxycodone, Ibuprofen, and other herbal supplements, which he is unable to recall currently. He recently relocated from out of state and is now establishing care with a new physician. He lives with his daughter and her family, who moved him in to stay with her because she was worried about his safety. Of note, the patient was recently diagnosed with chronic kidney disease (2 months ago) after he reported that he was titrating his dose of Lasix based on his daily weights. This information is provided to you by the intake nurse at your clinic, who is tasked with obtaining clinical histories on patients before being seen in the clinic.
As a clinic nurse, you must ensure that you call the patient before his first visit and ask that he bring all medications he is taking in a brown paper bag. Secondly, request that he be accompanied by his daughter if possible, given that she may be a source of additional clinical information as well as a caregiver who will potentially need medication regimens clarified. Thirdly, the nurse must attempt to obtain all medical records from the previous clinicians in other states. Fourthly, ensure that all medications include the name of the providing clinician and the date when they were started. The time of onset of medications is especially critical in this patient, given that he was recently diagnosed with chronic kidney disease but is currently taking multiple nephrotoxic drugs and is specifically taking one of them in excess. All of this information will prove critical for the clinician seeing the patient and could be useful in exposing potential prescription cascades in this patient taking over eight medications potentially prescribed by more than one prescriber.
The identification of polypharmacy does not necessarily mean the identification of potentially inappropriate medications. However, the risk is increased with polypharmacy. PIMs can contribute to negative clinical outcomes. The risk for potential negative outcomes is higher among the elderly and cancer patients.6
When prescribing medications to elderly patients, several tools can be used for better clinical outcomes. These include the Beers criteria, the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP), the Screening Tool to Alert to Right Treatment (START) criteria, and the Medication Appropriateness Index (MAI).6
The Beers criteria aim to identify potentially dangerous or ineffective drugs for older adults. It focuses on the list of medications that should be avoided or used with caution in patients 65 years or older, and the drugs are classified into five categories6:
The Beers criteria are the best known and most frequently used tool.
The Medication Appropriateness Index focuses on evaluating the key elements of appropriate prescribing, which are6:
One of the most frequently performed medical interventions performed by clinicians is writing a prescription. Pharmacotherapy is a vital part of the practice of medicine and in the maintenance of health wellness. There are innumerable conditions that rely on medication to alleviate, maintain, and slow the disease's progression. However, there are significant side effects associated with the use of medications. As such, every time clinicians prescribe a medication, the risk to benefit ratio must be carefully evaluated before deciding to prescribe. Every time a medication is administered, nurses must be aware of the side effect profile and remain vigilant to identify potential side effects.
Healthcare providers must remain valiant patient advocates while maintaining safe health practices. Polypharmacy is a major problem in this era of guideline-driven medicine, and all healthcare providers must each play a role as a checkpoint for the necessity of pharmacotherapy, especially in the elderly population.
