53: Addressing Polypharmacy & Improving Medication Adherence in Older Adults

Older adults are the largest consumers of prescription drugs. A large survey reported that more than one-half of patients 57–85 years old used at least 5 prescription medications, nonprescription medications, and nutritional supplements. Predictably, the number of medications steadily increased with the age of the patient. This survey also reported that 1 in 20 of these patients risked a major drug–drug interaction; half of these interactions included a nonprescription agent. Research demonstrates that polypharmacy is an independent risk factor for adverse outcomes, including hospitalization, nursing home placement, hypoglycemia, falls and fractures, pneumonia, and malnutrition, and death. Older adults are also generally less tolerant to the effects of a medication. This intolerance can manifest as an exaggerated effect of a medication or even a different effect as compared to younger patients, and is described at length in Chapter 9, “Principles of Prescribing for Older Adults.”

Table 53–1 lists several major problems caused by polypharmacy. The primary purpose of a medication also may be the source of an adverse drug reaction (ADR). A national study of emergency room patients showed that anticoagulants (including both warfarin and antiplatelet drugs) and diabetes drugs (including both insulin and oral medications) were responsible for two-thirds of all medication-related hospitalizations. In contrast, medications considered “inappropriate” by the Beer’s criteria accounted for only 7% of hospital admissions. Of these admissions, more than one-half were caused by digoxin alone.

Polypharmacy raises the risk of drug–drug and drug–disease interactions, particularly in older adults. The causes and consequences of such interactions are discussed in Chapter 9. In addition to known interactions, it is likely that clinically important interactions are yet to be discovered. Therefore, physicians should eliminate all unnecessary drugs, regardless of whether they are currently causing an obvious problem.

Similarly, polypharmacy increases the likelihood that patients will not adhere to their medication regimen. Nonadherence to medications contributed to 20% of the ADRs in an ambulatory setting. A number of factors may contribute to nonadherence.

Practice guidelines, for example, are primarily written by specialists for the management of a single condition. Physicians must then combine guidelines in an older patient with multiple conditions. For a hypothetical patient with chronic obstructive pulmonary disease, type 2 diabetes, osteoporosis, hypertension, and osteoarthritis, guidelines require 12 medications with multiple daily dosing regimens. Moreover, prescribing a drug may be easier than more time-consuming interventions such as lifestyle modification or nonpharmacologic treatments. Yet, patients may be less likely to adhere to medications as the regimen grows increasingly complex.

For both patients and the health care system, cost is also an important factor. The hypothetical patient described above would spend $406 each month on medication. It has been estimated that 25% of patients in Medicare part D plans and 40% of patients in employer-based plans are in the Medicare “doughnut hole.” When patients reach the doughnut hole, they must cover the cost of all medications until a maximum amount of money is spent in that year. In 2012, the doughnut hole exists between $2930 and $4700. Although the Affordable Care Act slowly eliminates patients’ Doughnut hole by 2020, cost remains a problem in health care. Therefore, medication reduction may benefit patient health, improve medication adherence, and reduce costs for patients as well as the overall health care system.

Despite clinicians’ best intentions to prescribe conservatively, as patients age and medical conditions accumulate, drugs frequently “pile up.” The problems listed in Table 53–1 can be ameliorated by decreasing the number and complexity of a patient’s medication regimen. At present, no study has demonstrated that trimming a patient’s medication list reduces morbidity or mortality. However, studies have demonstrated that pruning a patient’s medication list reduces the chance of adverse medication effects, lowers pharmacy cost, and improves patient compliance to their remaining medications. A Cochrane review of multiple systematic approaches to reduce inappropriate medications, for example, found that even with a modest reduction in the number of medications, ADRs could be reduced by 35%. For these reasons alone, unprescribing should become as routine a practice as prescribing.

The first step in assessing for inappropriate medications is to determine which medications the patient is taking (including dose and frequency). The traditional way of accomplishing this task is the “brown bag medication review,” in which the patient and/or family members collect and bring in all medications, including pills and creams, vitamins and supplements, herbal, and nonprescription medications. As each medication is removed from the brown bag, the physician (or office staff) can assess: (a) what the patient is actually taking; (b) what he/she understands about each medication; (c) the medication’s effectiveness; and (d) any suspected side effects. Finally, the provider updates the office medication list with the patient’s medications. This process may be time-consuming, but much of it can be completed by nonphysician office staff.

Approaches to unprescribing draw on evidence, expert opinion, physician judgment, and patient/caregiver preference. A number of approaches have been described to assist in assessing the appropriateness of a medication, including STOPP (Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions), MAI (Medication Appropriateness Index), and ARMOR (Assess, Review, Minimize, Optimize, Reassess). Figure 53–1 illustrates an approach to determine if a medication is a candidate for unprescribing. This approach is built on two published rubrics: the Good Palliative-Geriatric Practice algorithm and Holmes’ Model for Appropriate Prescribing for Patients Late in Life.

After conducting a “brown bag” review, step 2 requires the clinician to reconsider the evidence (or lack thereof) supporting each medication. Older patients are often excluded or underrepresented in trials and geriatric clinical guidelines are often extrapolated from studies of younger patients. Therefore, it is important to remember that what’s good for younger patients may not necessarily be good for older patients. Step 2 prompts clinicians to consider unprescribing when a patient is not “comparable” to the population originally examined in a research study. For example, a number of studies support the use of antihypertensive medications in older patients. Similarly, studies support the use of statins in some older populations. However, studies of digoxin for heart failure or atrial fibrillation are limited in older patients. Likewise, analyses of oral hypoglycemic agents or studies supporting specific target A1cs in older patients are scarce. The drugs that lack evidence may be candidates for unprescribing.

Step 3 requires the clinician to personalize the medication that “passed” Step 2. Holmes’ “Model for Appropriate Prescribing for Patients Late in Life” is useful. This model suggests that prescribing clinicians should apply 4 considerations to “filter” the medications that passed step 2. These considerations include: (a) the patients’ goals of care; (b) individualized treatment targets; (c) life expectancy; and (d) the drug’s “time until benefit.” Applying this model will result in a personalized set of medications.

To apply the Holmes model, the patient’s goals of care may range from curative to solely palliative; treatment targets may range from preventive to symptom management only. A drug’s “time until benefit” can vary from minutes (diuretics for congestive heart failure) to years (HMG CoA reductase inhibitors for primary prevention of coronary heart disease). For example, in an older adult with severe emphysema, a long-acting β-agonist inhaler is an evidenced-based, patient-appropriate medication because it improves symptoms in a short timeframe. Statins are also evidenced-based for this patient’s hyperlipidemia; however, the patient’s limited life expectancy would filter out this preventive medicine.

In step 4, the physician identifies any symptoms of an ADR. It is important to note that symptoms of an ADR may be subtle, such as fatigue or weakness. A good axiom to remember is that all new symptoms are caused by a medication until proven otherwise. The physician should consider unprescribing a medication when a new symptom occurs shortly after that medication was started. This approach will also avoid treating a new symptom by prescribing yet another medication.

In step 5, the physician must decide whether the potential for an adverse effect is likely. The “Beers” listing of potentially inappropriate medications is one helpful resource. Special scrutiny should also be applied to high-risk medications, including hypoglycemic agents, anticoagulation/antiplatelet medications, digoxin, narcotics, antianxiety/sleep aids, antidepressants, and medications with anticholinergic properties. If a drug is the likely cause of an adverse effect, it should be stopped. When unprescribing, clinicians must withdraw drugs carefully. When a medication requires titration up, for example, it will also require titration down. Titrating down is especially important for medications that promote tolerance, such as opiates, sedative-hypnotics, β blockers, clonidine, gabapentin, and selective serotonin reuptake inhibitors. Avoid abrupt, nondiscriminant “drug holidays,” and counsel patients to watch for withdrawal symptoms. (Exceptions to titrating down can be made in special circumstances where immediate discontinuation is required.) Finally, step 6 attempts to simply reduce the dose. Reducing dosage and/or frequency may also improve adherence. Further techniques to improve adherence are discussed in the next section.

Interventions beyond physician decision making can also improve prescribing practices. For example, attempts should be made to limit the number of providers who are prescribing medications for a given patient. Studies show that with each additional prescriber there is a 29% increase in ADRs. Likewise, using multiple pharmacies increases this risk. Therefore, clinicians should try to keep a patient’s medications with 1 prescriber and 1 pharmacy. Similarly, electronic prescribing (e-prescribing) also holds the potential to decrease the number of inappropriate medications in all patients by instantly reporting drug–drug and drug–disease interactions. E-prescribing programs generate an alert that is sometimes followed by a suggestion of a more appropriate medication. One analysis examined several trials that tested e-prescribing in the ambulatory, hospital, and nursing home settings. The majority of trials showed some decrease in inappropriate prescriptions. However, this decrease was variable, ranging from a decrease of 24% to less than 1%. In addition, excessive (and often irrelevant) alerts were not helpful, leading to “alert fatigue” for physicians. Although e-prescribing holds much promise, the magnitude of the effect on polypharmacy remains uncertain.

Improving Immediate Medication Adherence

In addition to prescribing only essential medications, prescribing clinicians must ensure that patients take the medicines that are prescribed. Centuries ago, Hippocrates noted that patients did not consistently take prescribed medicines. Today, multiple medications and frequent dosing regimens decrease adherence. Other factors that have been shown to influence medication adherence include inadequate education about the purpose, importance, and side effects of each medication, excessive cost, and limited physician knowledge of the indicators for a medication. Older adults also have additional medical and social challenges that may affect adherence. These challenges include difficulties in hearing and comprehending physician instructions, remembering discussions because of cognitive impairment, managing multiple medications with complex dosing regimens, accessing medications as a result of reduced social support, purchasing medications because of limited financial and transportation resources, and taking medications as a consequence of poor manual dexterity and vision. Patients may also take their medications intermittently, such as omitting diuretics before bedtime or social events. Together, these factors make nonadherence to medical treatments a serious and common concern in this age group. There may be good reasons that patients cannot adhere to their medicines. Clinicians should ask about barriers to adherence in a nonjudgmental way.

Physicians are often unable to identify which patients are not adhering to their medications; patients are also often reluctant to admit to nonadherence. However, physicians can directly improve many factors that affect medication adherence. Counting pills and asking patients and families about refill history, for example, can be helpful in identifying patients with adherence problems. Table 53–2 lists some simple, evidence-based interventions to improve adherence.

First and foremost, clinicians should always consider improving their relationship and communication with their patients as a means of improving medication adherence. Ultimately, the patient is responsible for taking medications, so a shared decision-making model is more likely to be successful in achieving adherence. A poor patient–provider relationship is likely to frustrate any attempt to improve medication adherence. Clinicians often are trained to believe that many medical problems are lifelong. However, patients may believe that medical problems can be “cured.” This belief is often reinforced by “high-tech” procedures that “fix the blockage” or “stop the bleeding.” To adhere to a medication, a patient must understand that an illness continues despite undergoing a medical procedure. The patient may believe that a medication is ineffective, unneeded, or simply not worth the expense. Even when the medication list is reduced, a patient may believe that he/she is taking too many medications, the side effects are too onerous, or a medication is frankly dangerous.

These misconceptions can be addressed only by effective patient–provider communication, including a discussion that emphasizes the chronic nature of a disease. A discussion of the long-term need for the appropriate medication should follow. Research suggests that poor communication commonly leads to medication nonadherence. Older adults report that they must understand the rationale for a medication before they will take it faithfully. Research also shows that many older adults are quite capable of understanding the purpose of a medication, despite the stereotypes to the contrary. The patient should receive education on the purpose, side effects, and length of time that each medication will be needed. This information is often complex, so a written summary may be needed.

Patients are keenly aware of medication cost. Certainly, patients will be unable to adhere if they cannot afford a medication. There is a clear relationship between the amount of a copayment and whether a patient will pick up a medication. Nonadherence rates triple when the copay reaches $50. Despite this, clinicians generally do not know the cost of most medications. Indeed, research shows that physicians underestimate the cost of expensive medications and overestimate inexpensive ones. This is understandable because drug costs change regularly, as new generics become available. Therefore, a pharmacist’s advice is important when choosing appropriate alternative medications. Although cost is certainly an important factor, nonadherence is still problematic in high-risk patients without cost constraints.

Finally, frequent dosing is associated with missed medications. Only 50% of patients adhere to medications that are dosed 4 times daily. Research demonstrates that reducing medication frequency improves adherence. Although combination pills and delayed-release preparations are often available, they are underutilized. Across a wide range of clinical settings, 15 randomized trials have demonstrated that combination pills improve adherence. Although individual dosing (bubble wrapping) also improves medication adherence, it is expensive and only available in special circumstances.

Improving Long-Term Medication Adherence

A considerable amount of research has examined the issue of long-term medication adherence. Research shows that adherence rates are higher when the duration of medication therapy is short, such as in acute illnesses. Adherence is much lower in chronic medications, decreasing dramatically within 6 months. Even in life-threatening conditions, adherence is poor. Only 40% of patients with acute coronary syndromes and 36% of those with stable coronary artery disease remained on statins at the second year of follow-up. Table 53–3 lists several interventions that might improve long-term adherence.

Patients are more likely to adhere to a medication if they believe that they have a medical problem. When a disease has symptoms, for example, adherence to medication is better. Therefore, when possible, clinicians should show patients evidence that demonstrates a medical condition exists and evidence of the beneficial effect of a medication. In general, regular contact between providers and patients is essential to improve and maintain medication adherence. Improved adherence was reported in a study where trained nurses regularly reinforced the need for hypertension medications. Importantly, older patients benefitted the most from this intervention. In a meta-analysis of 41 diabetic management studies, a consistent relationship was identified between frequency of contact and adherence to medication. Face-to-face interaction is critical. Research shows that education programs without a face-to-face visit do not change adherence. Therefore, primary care clinicians must see patients often to reinforce the importance of medications.

Awareness of the adverse effects of polypharmacy is quite broad. However, prescribing clinicians often wait for signs of an adverse drug event or reaction to discontinue the culprit medication. The practice of “unprescribing” medications to minimize the potential for adverse effects, to reduce pharmacy cost, and to improve a patient’s adherence to their remaining medications has yet to become habit. Several tools and algorithms are available to aid clinicians in unprescribing medications. Once a patient’s medication list has been trimmed, clinicians should then turn to techniques to increase medication adherence.