Published June 16, 2017 ADVERSE EFFECTS Addressing the Polypharmacy Conundrum Justin J. Sherman, PharmD, MCSAssociate Professor of Pharmacy Practice Leslie Davis, PharmD Candidate 2017 Kori Daniels, PharmD Candidate 2017University of Mississippi School of PharmacyJackson, Mississippi US Pharm. 2017;42(6):HS-14-HS-20. ABSTRACT: Polypharmacy has become a staggering problem in the United States, resulting in increased death and hospitalization, owing to patients—especially the elderly—who have multiple complex disease states and use a variety of providers and pharmacies. Pharmacists can address the polypharmacy conundrum through appropriate and thorough communication with patients and providers and through emerging concepts and programs such as medication therapy management, transitions of care, and refined computer systems that optimize the prescribing/filling process. Polypharmacy, the simultaneous use of multiple medications by a single patient for one or more conditions, has become a staggering problem in the United States. From 2000 to 2008, the percentage of Americans using at least one, two, or five prescription medications in the past month increased from 44% to 48%, 25% to 31%, and 6% to 11%, respectively.1 Prescription-related medication problems result in an estimated 119,000 deaths annually.1 Polypharmacy is especially problematic for the elderly. Eight or more prescription medications are used by 30% of this population daily, with an average of 18 prescription medications taken per year.1 In any given year, >175,000 elderly patients will visit the emergency room because of an adverse reaction to a commonly prescribed medication.1 How the Polypharmacy Problem Arises Many patients take medications to manage multiple chronic disease states. Clinical guidelines for these chronic diseases, such as hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and heart failure, frequently include recommendations for multiple medications added in a stepwise approach. Therefore, adherence to these guidelines can quickly lead to polypharmacy.2,3 An example of this may be seen in a patient being treated for type 2 diabetes, hypertension, and dyslipidemia, which are three common comorbid disease states. If this patient is prescribed three antihypertensives, two antidiabetics, and one lipid-lowering medication, as is often seen in management of these diseases, he or she may already have achieved polypharmacy. Use of multiple healthcare providers is common for the management of chronic diseases, including a primary care physician and various specialists. While each provider is responsible for completing a thorough assessment of the whole patient, a “silo effect” may occur in prescribing (i.e., concentrating only on one disease state). Additionally, patients may fill medications at multiple community pharmacies or through a mail-order pharmacy. This may cause pharmacists to fill prescriptions without knowing the patient’s entire medication regimen. Use of multiple providers and pharmacies to manage a patient without proper interprofessional communication can lead to therapeutic duplication or prescribing of medications with significant drug-drug interactions. If patients do not have at least one single provider who knows their complete medication regimen, the risk of polypharmacy increases greatly.2 Therapeutic duplication can result from prescribing by multiple providers. Duplication of medications in the same pharmacologic class or use of medications in different pharmacologic classes with similar side effects can also occur. This situation can lead to cumulative effects, as well as increased risk of adverse effect severity. If patients experience adverse effects that are unrecognized or misinterpreted by the healthcare provider, a prescribing cascade can result. For example, another drug could be inappropriately prescribed to treat a side effect that would have been alleviated by discontinuing the causative medication.4 The increasing use of technology in patient care, including electronic medical records, electronic-prescribing software, and pharmacy-dispensing software, has streamlined the prescribing process and improved the safety of prescribing. But with these systems, new challenges are arising. Alert overload and alert fatigue are phenomena that both the prescribing provider and the dispensing pharmacist can experience. These occur when prescribing and dispensing software create alerts and warnings for a variety of drug-related problems, including therapeutic duplications and interactions, which can be triggered regardless of their severity or clinical implications. When these alerts occur in high volume, providers may inadvertently disregard legitimate warnings, which can increase the patient’s risk of experiencing adverse events. The Consequences of Polypharmacy Adherence to a prescribed medication regimen often decreases as the number of medications and dosing complexity increase. However, adherence can be affected by a variety of factors, including patient-centered (e.g., health literacy, patient knowledge, physical difficulties), therapy-related (e.g., medication side effects, degree of behavior change required, medication taste), and healthcare system factors (e.g., long waiting time, lack of accessibility, prescriber continuity).5,6 Other categories of factors include social, economic, and disease-related factors.5,7 Pharmacists are ideally prepared to help overcome adherence barriers owing to their intense education and because of the counseling and motivational interviewing and daily treatment support they can provide.8 If a patient experiences any factor or multiple factors that affect adherence, he or she may stop taking the medications altogether without notifying the provider. The consequences of poor adherence are numerous and include potential disease progression, treatment failure, and unnecessary hospitalizations.4,5 As the number of prescribed medications increases, so does the risk of adverse drug events, hospitalizations, and death. Common drug classes associated with adverse drug events include cardiovascular medications, hypoglycemic medications, benzodiazepines, anticonvulsants, anticoagulants, antibiotics, and OTC medications (such as nonsteroidal anti-inflammatory drugs [NSAIDs] and acetaminophen).9 Many of these medications are frequently prescribed together, which can increase the risk of adverse effects and drug interactions. One population-based study found that outpatients taking five or more medications had an 88% increased risk of experiencing an adverse drug event compared to those who were taking fewer medications.10 It is also important to recognize that adverse reactions often manifest differently in older patients than in younger patients.4 Additionally, it is estimated that almost 100,000 emergency hospitalizations occur in the U.S. owing to adverse drug events, with 66% of these hospitalizations caused by unintentional overdoses.11 Polypharmacy often contributes to increased healthcare costs for patients and the healthcare system, and can manifest in a variety of ways. The most obvious example is the increased monthly copays that patients may incur as a result of a high number of prescribed medications. Furthermore, duplications in therapy or drug interactions may cause side effects that can increase outpatient visits as well as hospitalizations, which can then greatly increase medical costs for patients as well as the providers or hospitals that treat them.9 The consequences of polypharmacy are more common and often more severe in the elderly, as these patients are more likely to have multiple chronic conditions.12 Additionally, many consequences of polypharmacy are unique to this population because of age-related changes in body composition and function. These changes include altered body fat and water composition, decreased hepatic and renal function, and decreases in serum albumin levels. Each can alter the way bodies of the elderly react to various medications.4 Polypharmacy increases the risk of cognitive impairment, including delirium and dementia. Similarly, polypharmacy has been associated with functional decline, including a decreased ability to perform activities of daily living.9 An increase in the number of medications prescribed to elderly patients, especially of psychoactive drugs or antipsychotics, increases their risk of falls.2 One study demonstrated a strong association between the number of medications prescribed and the risk of falls in institutionalized patients, with a sudden elevation in risk starting at three drugs.13 How Pharmacists Can Address Polypharmacy Polypharmacy, especially in the elderly, can be addressed through several strategies. Pharmacists need to identify drug-related problems, prioritize them, reduce pill burden, eliminate unnecessary medication usage, and monitor for adverse drug-withdrawal events. Pharmacists can optimize medication therapy and improve therapeutic outcomes for patients through medication therapy management (MTM). Through the first of five core MTM elements, called the medication therapy review, pharmacists collect patient-specific information to identify and prioritize medication-related problems and create a plan to resolve them (TABLE 1). Pharmacists should stress to patients the importance of having and maintaining a current personal medication record (PMR).14 This record allows patients to have an active role in their healthcare and informs prescribers what they are taking. At a minimum, the patient should bring all prescription bottles to an appointment.15,16 Knowing what a patient is taking optimizes the medication regimen, and unnecessary or inappropriate medications are prevented from being prescribed. A medication-related action plan tells the patient what specific steps to take to resolve problems and gives the patient more control of his or her health status.14 Counseling Is Key Counseling should occur at every patient encounter. Educated patients are more likely to adhere to their medication regimen and be more willing to take an active role in their healthcare.17 Especially when the patient takes multiple medications for an indication, an explanation of how those medications work synergistically encourages the patient to become more adherent. As required by the Omnibus Budget Reconciliation Act of 1990, patients should be aware of the following for each medication in their PMR: the correct name (both brand and generic), dose, dose regimen, indication, any special circumstances regarding taking the medication (e.g., with food or not), how long the medication should be taken (e.g., lifetime vs. achieving some therapeutic goal), main adverse effects, and any monitoring that may be needed. Ensuring comprehension of these crucial but minimal counseling points is important. The “teach-back” method assesses whether the patient understands the counseling points.18 The pharmacist asks the patient a pointed question regarding the information provided, not to test the patient’s knowledge, but to see how well the pharmacist provided that knowledge and whether the patient actually understands how the counseling points apply to him or her. Ensuring that the patient’s caregiver and/or family members comprehend the counseling points is also important. Assessing the patient’s health literacy also may be necessary to maximize comprehension.19 Additionally, counseling should occur as needed concerning the disease state itself. While patients may know all of the parameters regarding their medications, they may not be aware of the therapeutic goals the prescriber is trying to achieve. Knowledge about the most likely therapeutic goals may assist in understanding why the medications are being used. This helps with overall adherence to the medication regimen when the patient feels part of the healthcare team in decision making. Also, patients have a sense of satisfaction when those therapeutic goals are achieved. For example, a patient newly diagnosed with type 2 diabetes who is being started on metformin might need counseling points on the medication (starting dose of metformin, expected titration, taking with food to prevent adverse effects, expected hemoglobin A1C [A1C] reduction) and on the disease state itself (goals of A1C reduction), as well as diabetes self-management education on checking blood glucose, signs and symptoms of hypo- and hyperglycemia and what action to take, lifestyle modifications of exercise and medical nutrition therapy, foot care, and sick-day management. Finally, it is also imperative that patients use only one pharmacy. Using multiple pharmacies allows for duplications and potentially interacting medications that could further complicate medication regimens. Pharmacists provide more efficient MTM services when they have a complete picture of the patient’s health status. Pharmacy computer systems bring up alerts when there is a potential interaction or duplication with a medication. The pharmacist evaluates the nature of the alert and ways to resolve the problem. In some instances, the pharmacist may need to contact the prescriber for resolution. Too often, pharmacists do not have time to make this call, so the alert may be overridden without action being taken. Since medications have different indications, one way some of these issues could be resolved would be inclusion of the indication on the prescription. This way, the pharmacist and the patient would know exactly why the medication is being taken. Benefits of Deprescribing Deprescribing is a term that has been proposed by prescribers to help minimize polypharmacy.20 It is a decision-making process aimed at tapering and/or stopping medications. Pharmacists may assist in this process by increasing providers’ awareness of instances amenable to deprescribing. Pharmacists collaborating with prescribers could determine the current indication for each medication in the PMR and help evaluate whether the medication is still conferring benefit. Medications are often unnecessarily continued. For example, long-acting nitrates or antidepressant medications may be continued for a past episode of angina or depression, respectively, when the original instances for use have been resolved. Antidiabetes or antihypertensive medications may still be on board in the PMR after diabetes or hypertension has responded to lifestyle modifications. Other considerations include whether the patient is even taking a particular medication and whether it fits into the patient’s life circumstances. For example, a patient with metastatic cancer may experience little benefit from a preventive medication like a statin. Finally, high-risk medications should be evaluated as to whether the benefit outweighs the potential for harm. These medications include opioids, benzodiazepines, anticoagulants, digoxin, psychotropic medications, and NSAIDs. Transitions of care provides important and unique opportunities to provide medication reconciliation. Medications are often stopped when a patient goes to the hospital in order to be compliant with the in-house formulary. Medications are added while inpatient to treat the problem. Those medications are not always stopped on discharge, while home medications are not always restarted. As required by law, the discharge physician or pharmacist will perform a line-by-line review of the patient’s home and inpatient medications to ensure that the patient is going home on all of the correct medications.21 However, medication reconciliation alone is not sufficient and should be combined with active patient counseling and a clinical medication review. A role for pharmacists has emerged for providing continuity of care to patients across healthcare settings.22 Current pharmacy computer systems have multiple warning tiers that produce alerts to help reduce duplications or interactions, but this can cause alert fatigue.16 Furthermore, alert fatigue can lead to the pharmacist’s overlooking these warnings and dispensing inappropriate medications. Adjusting the informatics software where only medium- to high-risk alerts are shown can decrease the number of alerts and help prevent alert fatigue. In addition, incorporating the Beers Criteria into informatics software can improve medication regimens for the elderly. Conclusions The polypharmacy conundrum can be addressed by optimizing communication with patients and providers; helping providers deprescribe when possible; and offering emerging opportunities to pharmacists, such as MTM, transitions of care, and refined computer systems that create a more seamless prescribing/filling process. REFERENCES 1. Polypharmacy Initiative Statistics. University of Louisville, Kentucky. http://polypharmacyinitiative.com/statistics.html. Accessed March 29, 2017.2. Polypharmacy: strategies for reducing the consequences of multiple medications. www.todaysgeriatricmedicine.com/archive/MJ16p24.html. Accessed March 18, 2017.3. Johansson T, Abuzahra ME, Keller S, et al. Impact of strategies to reduce polypharmacy on clinically relevant endpoints: a systematic review and meta-analysis. Brit J Clin Pharmacol. 2016;82:532-548.4. Preventing polypharmacy in older adults. Am Nurse Today. www.americannursetoday.com/preventing-polypharmacy-in-older-adults. Accessed March 16, 2017.5. Jin J, Sklar GE, Oh VM, et al. Factors affecting therapeutic compliance: a review from the patient’s perspective. Ther Clin Risk Manag. 2008;4(1):269-286.6. Hansen RA, Voils CI, Farley JF, et al. Prescriber continuity and medication adherence for complex patients. Ann Pharmacother. 2015;49(3):293-302.7. Costa E, Giardini A, Savin M, et al. Interventional tools to improve medication adherence: review of literature. Patient Prefer Adherence. 2015;14(9):1303-1314.8. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2014;29(11):CD000011.9. Maher RL, Hanlon JT, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57-65.10. Bourgeois FT, Shannon MW, Valim C, Mandi KD. Adverse drug events in the outpatient setting: an 11-year national analysis. Pharmacoepidemiol Drug Saf. 2010;19(9):901-910.11. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012.12. Cooper JA, Cadogan CA, Patterson SM, et al. Interventions to improve the appropriate use of polypharmacy for older people: a Cochrane systematic review. BMJ Open. 2015;5:e009235.13. Damian J, Pastor-Barriuso R, Valderrama-Gama E, de Pedro-Cuesta J. Factors associated with falls among older adults living in institutions. BMC Geriatr. 2013;13:6.14. American Pharmacists Association, National Association of Chain Drug Stores Foundation. Medication therapy management in pharmacy practice: core elements of an MTM service model (version 2.0). J Amer Pharm Assoc. 2008;48(3):341-353.15. Woodruff K. Preventing polypharmacy in older adults [online article]. Am Nurse Today. 2015;5(10). www.americannursetoday.com. 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Ensing HT, Stuijt CC, van den Bemt BJ, et al. Identifying the optimal role for pharmacists in care transitions: a systematic review. J Manage Care Spec Pharm. 2015;21(8):614-638. To comment on this article, contact rdavidson@uspharmacist.com.