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Polypharmacy refers to the practice of taking multiple medications. There is more to the concept of polypharmacy than just the actual number of prescriptions taken, however. Many potential problems can arise when certain medications are combined with each other, and when prescriptions are added to treat side effects caused by other drugs. Not surprisingly, the chances of polypharmacy increase as the patient ages, as do the chances for complications and medication–related problems to occur.

It’s important to recognize that many complex health conditions require a variety of prescribed and over–the–counter (OTC) medications for effective treatment. The term polypharmacy implies the need to work on or manage potential medication problems that often accompany the use of multiple medications by patients who live with comorbid medical conditions. During a comprehensive MTM process, the pharmacist can look at the whole medication regimen together, to identify how the medications might interact with each other and affect the individual. Alternatively, the pharmacist can perform a focused MTM where the goal is to work on specific problems. This may include problems with a particular medication, or the patient’s ability to monitor a medication’s effectiveness (i.e., blood pressure control). Through MTM, the pharmacist can work together with medical professionals and the patient to identify which medications are necessary and how to reduce the chances that use of multiple medications may cause harm.

What is Polypharmacy?

Polypharmacy is defined as “the concurrent use of multiple medications.”¹ Some definitions consider polypharmacy to be five or more drugs, but other definitions do not specify a number.

Data from the Agency for Healthcare Research & Quality (AHRQ) showed that in 2006 the average adult used at least four unique prescriptions. Senior citizens (over age 65) used approximately six different prescriptions per person. Some recent data on prescription drug use in the United States are summarized in Figure 1.² Among adults age 65 and older 90% had filled at least one prescription in the past 30 days and 41% had filled five or more.²

Figure 1. 2011 to 2014 Data on U.S. Prescription Drug Use2

Source: National Center for Health Statistics. Health, United States, 2016. Prescription drug use in the past 30 days, by sex, race, and age. United States, 2011–2014.

The total number of prescriptions filled by each person in a given year tells another part of the story. Kaiser Family Foundation data show that adults ages 19 to 64 filled an average of 7.5 to 21.5 prescriptions per person in 2016, depending upon the region. People ages 65 and over filled between 16 and 35 prescriptions per person (Figure 2).³ These numbers increase steadily each year, but a recent increase may reflect implementation of the Affordable Care Act (ACA, or Obamacare) which provided coverage to a large number of individuals who were previously uninsured.

Figure 2. Average Number of Prescriptions Filled in 2016 Per Adult (age 19 to 64)3

Source: Kaiser Family Foundation. Retail Prescription Drugs Filled at Pharmacies (Annual Per Capita). Timeframe 2016.

Why is Polypharmacy Increasing?

A number of healthcare and societal factors are driving the trend toward increased prescribing of medications. These include:^1,4.5

• A greater variety of available medications
• Increased pressure for physicians to prescribe to “satisfy” patients
• Greater awareness of drugs due to consumer drug advertising
• Patients seeing multiple physicians
• Patients using multiple pharmacies (including mail–order pharmacies)
• Transitions of care between hospitals, long–term care facilities, etc.
• The prescribing cascade (see below)

Medical reasons for polypharmacy include adding prescriptions or OTC agents:

• To treat a concomitant (coexisting) disease or disorder
• To treat a new or changing aspect of the illness (such as when a disease progresses)
• To treat or alleviate an adverse effect of a needed drug
• To boost or augment the desired effect of the drug
• To speed the onset of the desired effect

Unintentional causes of polypharmacy. In some cases, a prescribing physician is not fully aware of how many drugs a patient may be taking. This frequently occurs when a patient sees multiple physicians and fails to give a full medication history, either because the patient can’t remember the drugs, chooses not to report them, or lacks the ability to convey this information due to cognitive problems, language barriers, etc. Some of the other issues driving polypharmacy include the “prescribing cascade.” Usually, this term refers to the situation in which medications are used to treat the side effects of other medications—that is, using one drug to treat a problem with another drug (Figure 3).¹

Figure 3. The Prescribing Cascade

An example might be when a chemotherapy drug causes nausea, a medication is added to treat the nausea, but this agent causes headaches, so the patient uses an over–the–counter medication to treat headache. In some cases, the drug side effect is mistaken for a new diagnosis and the problem of polypharmacy escalates, as outlined in Figure 4.

Figure 4. In this dramatic example of the "prescribing cascade," a patient is treated for arthritis with a nonsteroidal anti-inflammatory drug (NSAID). These agents are known to be associated with hypertension. However, this is seen as a new condition, so a calcium channel blocker (CCB) is prescribed. When ankle swelling develops, a diuretic is added to the regimen to help clear fluids. Diuretic use can increase the risk of gout, especially in a patient already susceptible due to arthritis. When allopurinol is prescribed, the patient's condition deteriorates further.

Transitions of care. Polypharmacy often starts or increases during transitions of care.⁵ A patient may be discharged from the hospital with a different set of medications than those prescribed by the primary care physician, even if the underlying health problem did not change. The patient now has a new set of prescriptions from the hospital, and may have leftover medications at home that he or she is not sure how to fit in with the newly prescribed ones. Despite better efforts toward reconciling medication lists during care transitions in some facilities, polypharmacy often goes unrecognized and can lead to patient harm.^1,5,6

Drug advertising, and the pressure to prescribe. Few people would question that consumer advertising has driven the demand for prescription drugs in recent decades. Consumer advertising of pharmaceuticals continues to be successful in stimulating consumer demand for prescription drugs, especially as a greater variety of medications becomes available. Research shows that patients do initiate discussions with their doctors about advertised medications and ask for the products by name, as the ads intended. A survey of 500 physicians conducted by the FDA in 2004 revealed that most doctors believe that consumer drug advertising affects their interaction with patients. Other findings from the survey:⁷

• 78% of physicians believed their patients understood the possible benefits of an advertised drug very well or somewhat; 40% believed their patients understood possible risks of the drug
• 65% said they thought consumer ads confused patients about the relative risks and benefits of prescription drugs
• 75% of physicians surveyed said that DTC ads cause patients to think that the drug works better than it does
• 22% of primary care physicians said they felt "somewhat" or "very pressured" to prescribe a drug based on a patient request influenced by advertising
• 73% of PCPs and 63% of specialists said they thought patients came to the appointment expecting a prescription.

What Are Some of the Problems Associated With Polypharmacy?

Some of the common problems that occur with polypharmacy include an increased risk of drug–drug interactions, higher chances of experiencing drug side effects, and toxic effects due to long–term drug treatment.^8,9 An example of the latter might be toxicity of acetaminophen on the liver, or of nonsteroidal anti–inflammatory drugs (NSAIDs) on the kidneys. Other problems relate to how patients take the medication. Studies show that greater numbers of prescriptions and higher “pill counts” are associated with higher degrees of nonadherence. In addition, patients who take multiple medications are more likely to make mistakes between the agents and inadvertently take doses incorrectly as a result (e.g., mixing up two different–sized blue pills). Some of these problems have the potential to cause immediate harm, such as an overdose. However, in many cases, drug side effects are subtle and slow to evolve. They may be difficult to distinguish from “normal” aches and pains, or from the effects of the medical condition being treated. Some of the most common adverse effects that occur with medications are listed below:

• Stomach irritation (dyspepsia)
• Dry mouth (xerostomia)
• Headache
• Mental fogginess
• Agitation
• Appetite changes
• Changes in sleep (insomnia or hypersomnia)
• Dizziness leading to falls, accidents

The high economic costs of polypharmacy are also important to consider—even when relatively inexpensive medications are used, the cost of copayments and out–of–pocket expenses adds up when multiple chronic medications are used. Just one high–priced medication can put patients over the edge, or exceed their insurance plan’s allowance for drug spending. The effects of polypharmacy on an individual cannot always be predicted. Some patients are able to tolerate multiple medication regimens well, while others experience problems. This is due to individual differences in how people respond to drug treatment, including:

Pharmacokinetics The method and speed at which a drug is metabolized and moves through the body

Pharmacodynamics The effects of a drug on the body, including how the cells, receptors, and target organs respond

Pharmacogenomics Genetic differences that affect how a person responds to a drug

Pharmacodynamic and pharmacokinetic issues do not stay the same, but change throughout life. Pharmacogenomics is based on a person’s genetic makeup. Some aspects are set at birth, but diseases, medications, and the environment interact with genetic set points to evoke changes. (For example, people who are slow metabolizers can take drugs that induce them to be fast metabolizers). Pharmacokinetics and pharmacodynamics change as a person ages and affect drug absorption and risk of side effects.¹⁰ Polypharmacy is particularly a concern in older adults—this issue is discussed in detail in the next section, Module 8. Medication Use Among Older Adults.

Unfortunately, most pharmaceutical clinical trials do not provide a good overview of how a broad population of patients is going to respond to the drug.¹¹ Initial safety studies are conducted in healthy volunteers.¹² Most clinical trials for medications have a long list of “exclusion criteria”—people who do not qualify to enroll in the trial. Looking at these lists, you will see that the segment of the population in which the drug was studied does not often reflect the population using it: they may be older, have multiple medical problems, and take multiple medications.

Drug trials look at the effects in terms of a sample population as a whole, and are not actually designed to assess the effects in any given individual. People can respond very differently to medications. This is one of the reasons why MTM is so important. MTM does exactly what drug trials do not, which is to examine the effects of drug treatments on an individual, to assess each medication individually, and how they might interact when multiple medications are used.

MTM: How Pharmacists, Technicians, and Healthcare Providers Can Prevent and Address Polypharmacy

As noted above, MTM is tailored to address the issue of polypharmacy. During an MTM session, pharmacists trained in these methods can:

• Evaluate whether all the medications a person is taking are necessary: Are they effective? Safe, and/or do the benefits outweigh possible safety risks?
• Evaluate how the medications affect the person’s well–being and quality of life
• Explore ways to reduce costs of the medications (prescription and OTC)
• Determine whether certain medications can be discontinued, changed, substituted, or have a different dosage or administration method

Table 1. Prescribing Checklist to Prevent Unnecessary Polypharmacy

Indication Is the medication appropriate for this patient? Does each medication on the list have an appropriate indication? Effectiveness Are treatment goals being met? Is the medication the most effective available? Safety Is the dose appropriate for the patient? Are there long–term risks associated with the drug? Does the patient have signs of adverse drug effects or interactions? Adherence Will the patient be able to follow directions for use and remember to take? Are there barriers that could prevent the patient from using the drug correctly? (e.g., difficulty handling the container or administering the medication; visual impairment) Is the cost of the medication a factor in the patient’s adherence?

Technicians involved in MTM services should understand why polypharmacy is a concern, and the goals of MTM in relation to reducing the potential risks of polypharmacy. Technicians may be involved in developing a Personal Medication List (PML) and may recognize some of the possible warning signs of polypharmacy to alert the pharmacist (e.g., when certain high–risk drugs are being used together). Technicians may have a role in reminding patients to follow through with monitoring steps (for example, blood tests) to identify adverse effects of medications. Technicians who have high levels of interaction with patients or medical/nursing staff (i.e., in hospitals) are in a unique position to gather information about commonly overlooked factors, such as hidden supplement use, or patient refusal to take a medication.

Challenges in Managing Polypharmacy

Problems associated with polypharmacy are not always easy to detect and may also be frustrating to overcome. A number of challenges may arise when the pharmacist and technician team attempt to address issues in polypharmacy.

• The timing of adverse drug reactions is not always immediate, and thus cannot always be traced to adding a new drug or changing a dose.
• Use of OTC medications and supplements may be overlooked. Patients frequently neglect to report them or may add new ones without discussing this with the physician or pharmacist. Many consumers assume that when a medication is OTC, it is benign, or safe enough to not be associated with any drug interactions or adverse events.
• Many patients have multiple old or outdated prescriptions, and are not sure what they’re taking or supposed to take
• Medical and pharmacy records related to multiple drugs may be unclear

Sometimes, when the MTM session does not yield a clear sense of what the patient is taking, the pharmacist conducting MTM may ask the patient to conduct an at–home “medication administration record” for a certain time period, usually about 30 days. During this time, patients are asked to record:

• What they have taken
• When (what times) they are taking it
• Any missed doses that occur
• Effects they notice while taking the drug (efficacy, possible side effects)
• Issues in daily living that may be related: diet, sleep patterns, etc.

How a patient takes a drug is an important issue and may provide important clues to how the drugs work for them and whether side effects occur. Some examples include:

• Taking certain medications (such as the thyroid medication lexothyroxine) along with foods or other drugs can interfere with how the drug is absorbed in the body. Patients may not get the benefits of the drug as intended.
• Other medications should be taken with food to reduce possible gastrointestinal upset. A number of common antibiotics fall into this category.
• Is the person crushing a tablet that is not meant to be crushed, or opening up a capsule to “sprinkle” over food instead of swallowing it whole? While it may seem obvious that people should avoid “breaking the rules” when taking their medications, most
• consumers do not recognize how a sustained–release tablet works and that the way it is swallowed affects whether the drug is released into the body as intended.
• Drug allergies are another possible source of confusion. Consumers may not recognize classic signs of actual drug allergy (rash, hives, chest tightness or difficulty breathing). They may assume they are “allergic” to a drug if it caused them to vomit at some point, or caused headaches.

Conclusion

Polypharmacy cannot always be avoided. Certain complex disease states—such as diabetes, cancers, cardiovascular diseases—require a number of medications to control the disease and to minimize its effects on the individual. A person who has had a stroke or heart attack is usually prescribed several medications to reduce the risk of mortality or another catastrophic event. In this sense, polypharmacy is not necessarily the enemy. But, patients who take multiple medications can always benefit from a careful review and individual assessment of whether they are safe, necessary, effective, cost–effective, and taken properly.

References

1. Antimisiaris D, Cheek DJ. Polypharmacy. In: Mauk KL. Gerontological Nursing. Burlington, MA: Jones & Bartlett. 2014:417–456.
2. National Center for Health Statistics. Health, United States, 2016. Prescription drug use in the past 30 days, by sex, race, and age. United States, 2011–2014. Available at: https://www.cdc.gov/nchs/data/hus/hus16.pdf#079.
3. Kaiser Family Foundation. Retail Prescription Drugs Filled at Pharmacies (Annual Per Capita). Timeframe 2016. Available at: https://www.kff.org/other/state–indicator/retail–rx–drugs–by–age/?currentTimeframe=0&selectedDistributions=ages– 65&sortModel=%7B%22colId%22:%22Ages%2065%2B%22,%22sort%22:%22desc%22%7D
4. Gamble JM, Hall JJ, Marrie TJ, et al. Medication transitions and polypharmacy in older adults following acute care. Ther Clin Risk Manag. 2014;10:189–196.
5. Patterson SM, Cadogan CA, Kerse N, et al. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2014;10:CD008165.
6. Tamura BK, Bell CL, Inaba M, et al. Outcomes of polypharmacy in nursing home residents. Clin Geriatr Med. 2012;28(2):217–236.
7. Aikin KJ, Swasy JL, Braman AC. Patient and physician attitudes and behaviors associated with DTC promotion of prescription drugs. Summary of FDA survey research results. Food and Drug Administration, Nov 19, 2004. Available at: https://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ucm109877.pdf
8. Tannenbaum C, Sheehan NL. Understanding and preventing drug–drug and drug–gene interactions. Expert Rev Clin Pharmacol. 2014;7(4):533–544.
9. von Lueder TG, Atar D. Comorbidities and polypharmacy. Heart Fail Clin. 2014;10(2):367–372.
10. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65.
11. Niederseer D, Thaler CW, Niederseer M, et al. Mismatch between heart failure patients in clinical trials and the real world. Int J Cardiol. 2013;168(3):1859–1865.
12. Magid DJ, Estabrooks PA, Brand DW, et al. Translating patient safety research into clinical practice. In: Advances in Patient Safety: From Research to Implementation (Volume 2: Concepts and Methodology). Rockville MD; 2005.

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