COMMENTARY

Polypharmacy: A Five-Step Call to Action for Family Derjung M. Tarn, MD, PhD; Janice B. Schwartz, MD

(Fam Med. 2020;52(10):699-701.) doi: 10.22454/FamMed.2020.909136

here has been immense progress with medical conditions received polypharmacy in drug development for the prevention 2015-2016.7 Adults aged 65 years and older and treatment of diseases since around took a median of four prescription , T 8 1500 BC, when an ancient Egyptian medical with 39% taking more than five. Over the next papyrus described the first pills.1 Today, over decade, it is estimated that polypharmacy will 20,000 drugs are approved by the Food and result in over 4.6 million hospitalizations and Drug Administration (FDA) for marketing in 150,000 premature American deaths.9 Thus, the United States.2 Clinical guidelines recom- polypharmacy is a major public health prob- mend medications for use, and pro- lem. viders routinely prescribe them. Medicine has A number of different strategies have been moved from plant powders, honey, and grease proposed and tested to address polypharmacy to evidence-based medical therapies, but these and reduce the number of medications that advances are not without consequence. Phy- patients take. These include approaches such sicians have created a new iatrogenic medi- as: (1) avoiding the addition of a medicine to cal condition—that of polypharmacy, or the treat the unwanted effects of another medicine, concurrent use of multiple medications by a sometimes referred to as the prescribing cas- patient. cade (eg, when a patient prescribed a calcium The literature most commonly defines poly- channel blocker develops peripheral edema as taking five or more concomitant and receives an inappropriate new prescrip- medications, but consensus is lacking about tion for a loop diuretic)10-12; (2) ensuring that the exact definition. Numerical definitions treatments are not continued for longer than range from two to 11 or more concomitant originally intended (eg, , pro- medications.3 Some definitions consider ap- ton pump inhibitors, )13; and propriateness of prescribing, and some include (3) of high-risk medications us- over-the-counter medications and dietary sup- ing complex multifaceted approaches involving plements.3,4 While no universal agreement ex- interdisciplinary teams of physicians, pharma- ists about the exact definition of polypharmacy, cists, and nurses.14 Deprescribing approaches the data do suggest that many patients take have included establishing lists of high-risk too many medications. or inappropriate medications, and The evidence clearly shows that the risk and other health care professional education of potential drug-drug interactions increases about strategies for reducing the use of these steeply with the number of concomitant drugs taken. The risk for interactions reaches 50% From the Department of Family Medicine, David Geffen with the coadministration of four medications School of Medicine at UCLA, University of California, Los and approaches 100% with 10 concomitant Angeles, Los Angeles, CA (Dr Tarn); and Department of 5,6 Medicine and Bioengineering and Therapeutic Sciences, medications. Over one fifth of typical out- University of California, San Francisco, San Francisco, CA patients aged 40-79 years with stable chronic (Dr Schwartz).

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medications.15,16 National campaigns have fo- and/or telehealth settings. For family medicine cused on reducing the use of individual agents trainees, reconciliation sessions such as atypical or but could be a required part of their curriculum. have not focused on the use of multiple medi- These sessions would provide trainees with cations as a risk factor for adverse medication patient-based learning that includes interdis- effects.17 Despite efforts over many decades, ciplinary sessions with pharmacists, clinical polypharmacy persists.14 pharmacologists, and nursing colleagues. Some may wonder about the link between direct-to-consumer advertising (DTCA) and 3. Leverage EHR Capabilities to polypharmacy. However, since only a few Provide Point-of-Care Suggestions and countries allow DTCA and polypharmacy is a Advice to Address Polypharmacy worldwide problem, DTCA is likely not a major EHRs can be programmed to provide alerts to contributor to polypharmacy. The sparse data prescribers when they prescribe or refill high- available on this issue also do not provide evi- risk or inappropriate medications, or when dence to link DTCA and polypharmacy, as few medications are prescribed for longer than typ- patients report expecting prescriptions based ically needed. But alert fatigue comes into play, on advertisements.18 and alerts without advice on specific actions There is a need for effective methods to ad- to take are largely ineffective. Family physi- dress polypharmacy, particularly in the pri- cians must participate in the development and mary care setting. We propose five steps for testing of actionable notifications when auto- physicians, practices, health sys- mated or electronic systems flag polypharmacy. tems, and organizations to take: Successful examples of these approaches exist for integrating pharmacogenomic information 1. Know the Number into clinical practice19 and for informing phy- Put polypharmacy in the spotlight by requir- sicians about patients’ Drug Burden Index.20 ing documentation of the total number of medi- It is time to implement polypharmacy reduc- cations taken by patients at every encounter. tion algorithms to reduce the adverse effects Medical records and electronic health record of medications. (EHR) systems currently contain lists of pa- tient medications, but display of the total num- 4. Lobby for Adequate Time ber of medications does not occur. We propose and Reimbursement to that EHRs routinely prompt primary care phy- Evaluate Polypharmacy sicians to enter the total number of medica- Primary care physicians need adequate time tions a patient is taking, for example as a sixth and reimbursement to identify and address vital sign, and that this information is promi- polypharmacy. These activities may include nently displayed in the EHR. The EHR could thorough review of patient medications and prompt physicians to update the total num- medical problems to determine appropriate- ber of medications if patient medication lists ness of prescribing, consideration of multiple change, or could be programmed to require drug-drug interactions and economic/pill bur- physician entry of the number of patient medi- den, identification of potential deprescribing cations before medications are prescribed. In targets, consultation with pharmacists or spe- the absence of an EHR, the information could cialist physicians who often prescribe a subset be determined by a physician and entered with of patient medications, assessment of patient the vital signs at every encounter. goals of care, and counseling of patients and/ or care partners. These activities often occur 2. Initiate Quality Improvement Efforts outside of in-person patient encounters and to Reduce Polypharmacy at Every Level historically have been largely nonreimbursed. For practitioners, one approach could be to mandate a performance improvement activ- 5. Engage in Polypharmacy Research ity on polypharmacy for board recertification We need to develop an evidence base to replace by the American Board of Family Medicine. current guidelines, focused on single diseas- These activities typically prompt physicians to es, with guidelines to treat patients who have implement and measure the effect of a change multiple chronic medical conditions.21 In ad- in their practice. The polypharmacy perfor- dition, family physicians are needed to help mance improvement activity could be required establish standards for identifying polyphar- for clinically active family physicians who pro- macy, from developing a standard definition vide care for continuity patients in outpatient of the term to determining which prescription

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medications, over-the-counter medications, and 8. Charlesworth CJ, Smit E, Lee DSH, Alramadhan F, Odden dietary supplements (which are often taken MC. Polypharmacy among adults aged 65 years and older in the United States: 1988-2010. J Gerontol A Biol Sci Med sporadically) should be included when assess- Sci. 2015;70(8):989-995. ing polypharmacy. We also need to identify best 9. Brownlee S, Garber J. Medication Overload: America’s Other practices for minimizing the number of con- Drug Problem. Brookline, MA: The Lown Institute; 2019. comitant medications without compromising 10. Rochon PA, Gurwitz JH. The prescribing cascade revisited. therapeutic goals. Lancet. 2017;389(10081):1778-1780. The prescription of multiple medications is 11. Savage RD, Visentin JD, Bronskill SE, et al. Evaluation of a common prescribing cascade of calcium channel blockers and clearly beneficial in selected patients. None- diuretics in older adults with . JAMA Intern theless, physicians must take responsibility Med. 2020;180(5):643-651. for solving the iatrogenic problem of polyphar- 12. Vouri SM, van Tuyl JS, Olsen MA, Xian H, Schootman M. macy. We must implement strategies for the An evaluation of a potential calcium channel blocker-lower- extremity edema-loop diuretic prescribing cascade. J Am routine identification and reduction of poly- Pharm Assoc (2003). 2018;58(5):534-539.e4. pharmacy. Family physicians are well posi- 13. Mangin D, Lawson J, Cuppage J, et al. Legacy drug-prescrib- tioned to tackle this problem as they have ing patterns in primary care. Ann Fam Med. 2018;16(6):515- long-standing relationships with patients, 520. knowledge of the entire spectrum of a patient’s 14. Rankin A, Cadogan CA, Patterson SM, et al. Interventions to improve the appropriate use of polypharmacy for older medical problems, and of patient goals of care. people. Cochrane Database Syst Rev. 2018;9:CD008165. We need action now, before this burgeoning 15. 2019 American Society Update public health problem becomes a global poly- Expert Panel. American Geriatrics Society 2019 Updated pharmacy epidemic. AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. CORRESPONDING AUTHOR: Address correspondence to 16. Gallagher P, O’Mahony D. STOPP (Screening Tool of Older Dr Derjung Mimi Tarn, David Geffen School of Medicine Persons’ potentially inappropriate Prescriptions): application at UCLA, Department of Family Medicine, 10880 Wilshire to acutely ill elderly patients and comparison with Beers’ Blvd, Ste 1800, Los Angeles, CA 90024. 310-794-8242. Fax: criteria. Age Ageing. 2008;37(6):673-679. 310-794-6097. [email protected]. 17. US Department of Health and Human Services - Office of Disease Prevention and Health Promotion. National Action References Plan for Adverse Drug Event Prevention. 2014. https:// health.gov/sites/default/files/2019-09/ADE-Action-Plan-508c. 1. Target Health LLC. A Short History of Pills. https://www. pdf. Accessed August 11, 2020. targethealth.com/post/a-short-history-of-pills. Published November 20, 2017. Accessed August 11, 2020. 18. Aikin KJ, Swasy JL, Braman AC. Patient and Physician Attitudes and Behaviors Associated with DTC Promotion of 2. US Food and Drug Administration. Fact Sheet: FDA at a Prescription Drugs: Summary of FDA Survey Research Re- Glance. October 2019. https://www.fda.gov/about-fda/fda- sults. November 19, 2004. https://www.fda.gov/media/112016/ basics/fact-sheet-fda-glance. Published October 2019. Ac- download. Accessed September 2, 2020. cessed August 11, 2020. 19. Overby CL, Tarczy-Hornoch P, Kalet IJ, et al. Developing a 3. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What prototype system for integrating findings is polypharmacy? A systematic review of definitions. BMC into clinical practice. J Pers Med. 2012;2(4):241-256. Geriatr. 2017;17(1):230. 20. Kouladjian O’Donnell L, Gnjidic D, Chen TF, Hilmer SN. 4. Cadogan CA, Ryan C, Hughes CM. Appropriate polyphar- Integration of an electronic Drug Burden Index risk as- macy and medicine safety: when many is not too many. Drug sessment tool into Home Medicines Reviews: deprescribing Saf. 2016;39(2):109-116. anticholinergic and medications. Ther Adv Drug 5. Johnell K, Klarin I. The relationship between number of Saf. 2019;10:2042098619832471. drugs and potential drug-drug interactions in the elderly: 21. Farmer C, Fenu E, O’Flynn N, Guthrie B. Clinical assess- a study of over 600,000 elderly patients from the Swedish ment and management of multimorbidity: summary of NICE Prescribed Drug Register. Drug Saf. 2007;30(10):911-918. guidance. BMJ. 2016;354:i4843. 6. Steinman MA, Miao Y, Boscardin WJ, Komaiko KD, Schwartz JB. Prescribing quality in older veterans: a multifocal ap- proach. J Gen Intern Med. 2014;29(10):1379-1386. 7. Hales CM, Servais J, Martin CB, Kohen D. Prescription drug use among adults aged 40-79 in the United States and Canada. NCHS Data Brief. 2019;(347):1-8.

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