US Pharm. 2011;36(5):45-48.

Medication adherence is the voluntary cooperation of the patient in taking drugs or medicine as prescribed, including timing, dosage, and frequency. The term concordance, which has developed over the past decade, is based on the patient-centered philosophy that the patient and the health care provider (HCP) play equal roles in medication decision-making.1 These terms have replaced the term “compliance,” which places no emphasis on the patient’s contribution to the patient–physician relationship.2 Good adherence is especially important in the management of chronic diseases.

Chronic diseases account for 70% of all deaths and are the leading cause of morbidity and mortality in the United States.3 Approximately 20% to 50% of patients are nonadherent to their medications.4 Nonadherence to medication for chronic diseases leads to worse therapeutic outcomes, higher hospitalization rates, and increased health care costs.4 Patients with chronic conditions often must take more than one medication indefinitely for maintenance, and their adherence to their therapeutic regimen tends to decrease over time.3

It is estimated that poor adherence costs $100 billion annually in the U.S.5 Nonadherence may be voluntary or involuntary, and there are many reasons for patients not taking their medication as prescribed.2

Reasons for Nonadherence

Some reasons for not taking medication are involuntary, such as forgetfulness. Some are voluntary, such as fear of adverse events or a negative attitude toward medications in general.6,7 Other reasons include high cost; complex regimen; lack of education; poor quality of life; busy schedule; poor patient–physician relationship; perceptions of disease severity and drug effectiveness; asymptomatic disease (e.g., hypertension, diabetes, hyperlipidemia); depression; stress; lack of social support; poor coping skills; substance abuse; and low literacy.6-9

Since nonadherence to antihypertensive medication is the main cause of uncontrolled blood pressure (BP), Tsiantou et al studied a hypertensive Greek population (n = 47) to find out why they did or did not take their antihypertensive medications as prescribed.10 In either a focus group or a one-on-one interview, patients discussed their attitudes toward their disease and the drugs they were prescribed. Factors facilitating adherence included perceived seriousness of the disease; acceptance of having a chronic disease requiring lifelong treatment; time of dose (many preferred morning dosing and often associated their medication with breakfast); and good patient–physician relationship with reinforcement for positive efforts and results. Reasons for nonadherence were negative attitude toward drugs in general; adverse drug reactions; drug effects (e.g., skipping a diuretic if planning to be out for the day); number of doses; and lack of symptoms. One patient reported that he stopped his medicine when his BP was within acceptable limits.10

Measuring Adherence

In research, there are several ways to measure adherence. Medication event monitoring systems (MEMS) are the most accurate method of measuring adherence because they record the date and time the medication bottle was opened through microprocessor technology embedded in the cap.3 MEMS can be erroneous, since the patient may remove more than one dose at a time or open the bottle without removing a dose.3,6 MEMS are expensive, and a different device is needed for each medication. This is an impractical way to determine adherence in clinical practice. Patient self-report, pill counts, pharmacy databases or refill rates, and blood levels, which also are employed in research, are more feasible options for clinical practice.3,6,9

Patient self-report is probably the easiest way to determine adherence, but there are obvious problems with this method. To please his or her HCP, the patient is likely to report taking medication more often than is actually the case. When adherence is being assessed, open-ended questions should be asked. Instead of asking, “Are you taking your medications?” the HCP should phrase the question along the lines of, “How many times in the past week (month) have you skipped your medications?”6

Morisky’s Medication Adherence Scale (MMAS) was designed to distinguish poorly adherent patients from those with medium-to-high adherence to their antihypertensive regimen (TABLE 1).9 MMAS consists of questions addressing multiple reasons for nonadherence; e.g., because regimen complexity can lead to noncompliance, the scale contains a question assessing whether the patient feels hassled about his or her regimen. Since patients tend to give their HCPs positive answers to please them, the questions in Morisky’s study were phrased to avoid this bias. Each question measures a specific medication-taking behavior rather than adherence or compliance behavior.9

More than 1,300 hypertensive patients participated in the study. A baseline interview was conducted to assess demographic characteristics, medical history, health behaviors, appointment-keeping, and medication adherence, and BP was measured at all outpatient visits over the next 6 months. The mean value of the BP measurements was used to determine adherence, with systolic BP >140 and diastolic BP >90 denoting uncontrolled hypertension.9

The correlation between BP control and high scores on the adherence scale was statistically significant. Variables associated with medication adherence were knowledge, patient satisfaction, coping skills, stress level, and regimen complexity.9 MMAS correlated with pharmacy fill rates. The scale had 93% sensitivity (identifying noncompliant patients), but only 53% specificity (identifying compliant patients); therefore, it is a less valuable tool for identifying patients with uncontrolled BP who adhere to their medication regimen.9

Pharmacist Interventions

Once the reasons for nonadherence have been determined, the pharmacist can intervene to help the patient achieve a better therapeutic outcome.9 Often, many strategies must be employed to improve adherence, including counseling, patient education, and memory enhancement.8

Improved patient-centeredness (involving the patient in decision-making) can lead to improved adherence.2 Simplifying the medication regimen through once-daily dosing formulations can result in as much as twice as many adherent days versus more complex dosing.3 Improving the patient–physician relationship is a commonly proposed means of enhancing compliance.5 A patient’s attitude may also affect his or her adherence.11

A behavioral model of medication adherence that is based on the theory of planned behavior has been proposed.11 This model posits that the patient must have a basic understanding of the disease in order to make informed decisions about his or her medication. This information should be individually tailored to the patient and must be presented by the HCP in easily understandable language.

According to the model, the patient’s intention to adhere to his or her regimen is based on three things: subjective norm, attitude, and perceived behavioral control.11 Subjective norm is the patient’s beliefs about what others think he should do and his or her motivation to do these things; the pharmacist can help change the patient’s perception of the norm or his or her motivation to comply. Attitude is the patient’s beliefs about the outcomes of these behaviors and his or her perceptions of these outcomes (e.g., taking my medicine will keep me healthy, which is better than feeling sick). The pharmacist can positively influence attitude by explaining the benefits of adherence (e.g., better quality of life). Perceived behavioral control refers to the patient’s perceptions of how easy or difficult it is to take the medication and how much control the patient believes he or she has over taking them; e.g., a patient with a demanding job may forget or lack adequate privacy to take his or her medication. In attempting to modify perceived behavioral control, it is most beneficial to make small, simple changes (e.g., using a dose organizer). These modifications must occur in a setting where the patient feels confident of successfully performing the behavior every day.11

Another adherence tool was shown to be effective in a study involving low-health-literacy patients with coronary heart disease.12 A pill card was developed that served as a graphic aid to improve health literacy and adherence in this population. The card was designed to give the least amount of necessary information. A color image of the pill, the indication, directions, and time of administration (morning, afternoon, evening, or bedtime) were displayed on the card.  Nearly all subjects considered the card an easy and useful tool for understanding their medical treatment. Subjects who used it most frequently had limited literacy, less education (approximately half of subjects had not completed high school), or cognitive impairment.12

Many studies have been done to determine whether pharmacist interventions can lead to improved adherence and treatment outcomes. In a large meta-analysis conducted to determine medication adherence (along with several other outcomes), pharmacist interventions were found to improve medication adherence (P = .001).13

A systematic review of 15 studies of hypertensive patients was conducted to determine adherence and BP control as a result of pharmacist interventions.14 The interventions were medication management (regimen simplification, resolving adverse drug reactions, and monitoring or adjusting drug therapy); patient education (on hypertension and lifestyle modification or BP self-monitoring); BP self-monitoring and documentation, including education, encouragement, and validation; medication reminders (adherence aids or telephone- or computer-based appointment reminders); improved administration system (MEMS or blister packs); increased follow-up appointments or contacts; HCP (e.g., physician or nurse practitioner) educational interventions; and visits with a clinical pharmacist. Significant improvements in clinical outcomes (systolic, diastolic, or controlled BP) occurred in 88% of studies; however, only 44% had significant increases in adherence. The difference in improved adherence and improved clinical outcomes was proposed to be due to medication adjustments made by pharmacists; if a regimen was improved, BP could be improved without a change in adherence.14

A systematic review examined 37 studies of hypertensive patients in which an intervention was performed by a pharmacist or nurse.6 Interventions that were associated with a reduction in systolic BP were pharmacist medication recommendation to the physician (–27.2 mmHg, P = .002); counseling regarding lifestyle modifications (–12.6 mmHg, P = .033); intervention performed by pharmacist (–11.7 mmHg, P = .028); use of an algorithm (–8.46, P <.001); and completion of a drug profile (–8.28, P = .001). Factors associated with a reduction in diastolic BP were referral to a specialist (–19.6 mmHg, P = .039); patient education about BP medications (–17.6 mmHg, P = .003); completion of a drug profile (–7.3 mmHg, P = .006); intervention performed by a pharmacist (–4.0 mmHg, P = .044); and intervention performed by a nurse (–3.9 mmHg, P = .041).6

Another systematic review examined studies of informational (n = 12), behavioral (n = 10), and combined interventions (n = 15).4 In the informational studies, counseling was done by a physician, nurse, health educator, or pharmacist. Clinical outcomes were not improved in eight informational studies; the positive clinical outcomes in the remaining four informational studies (interventions involving fairly intensive counseling with reinforcement over time) ranged from slight improvement to large improvement. The most successful behavioral interventions were dosing simplification and repeated assessment of medication use with feedback. Specialized packaging, direct observation of medication ingestion, and cognitive behavioral therapy were used in other behavioral studies, but did not result in improved adherence or therapeutic outcomes. All but two combined-intervention studies had both informational and behavioral components; the other two used social-support measures combined with informational or behavioral strategies.  Five informational and behavioral studies showed clear improvement in adherence, and three others reported mixed or nearly significant improvement. There was no significant improvement in all of the measured clinical outcomes in these studies; however, several studies reported a significant change in at least one clinical parameter. The two studies using social-support strategies led to better compliance, but not improved outcomes.4

A retrospective cohort study of 73 HIV-positive patients investigated whether interventions (minimizing dosing frequency and/or pill quantity) by an HIV clinical pharmacist had an effect on adherence.7 Specifically, the effect of simplifying the medication regimen on adherence to antiretroviral (ARV) therapy was assessed. The pharmacist employed the following measures; using combination medications, eliminating ARVs that required separate dosing, and trying to minimize adverse effects. In addition, patients were educated about medication adherence and adherence strategies. The daily pill quantity was reduced from 7.2 ± 3.9 pills to 5.4 ± 2.8 pills (P <.001), and the daily dosing frequency was reduced from 2.0 ± 0.5 times to 1.5 ± 0.5 times (P <.001). Based on electronic refill records, these modifications resulted in an improvement in adherence from 81% to 89% (P = .003). A statistically significant increase in CD4+ cell count and decrease in HIV viral load were noted at 6 months postintervention.7

Role of the Pharmacist

While medication dispensing is the best-known function of the pharmacist, pharmacists—through counseling, medication therapy management (MTM), disease-state management, and other means—can play a pivotal role in patient care. There are opportunities in every type of pharmacy practice to improve patients’ adherence and therapeutic outcomes, and pharmacists must embrace and act on them.

With the new health care reform laws—the Patient Protection and Affordable Care Act, in particular—there may be reimbursement for such activities. The patient-centered medical home model of health care delivery will allow the pharmacist to be part of a physician- or nurse practitioner–led health care team. Pharmacists will be compensated for delivering MTM services to their patients.6,15

Many factors dictate a patient’s medication adherence, and each patient is unique. The pharmacist must approach each patient individually to determine the level of adherence and what barriers may exist that are preventing the patient from taking his or her medication appropriately.

Education, while helpful, is usually not enough to persuade the patient to comply with the physician’s drug orders. Information must be presented in clear, easy-to-understand language, and the patient must understand not only the benefits of adherence, but the repercussions of nonadherence. Also, positive reinforcement goes a long way; patients who feel empowered and cared for are more apt to play an active role in their treatment.

Dosing simplification and minimization of adverse effects are extremely successful strategies for improving adherence. When filling a prescription, the pharmacist should do a quick review to see whether the dosing schedule is as simple as possible. The pharmacist should inquire frequently about any adverse effects the patient is experiencing and then consult the physician regarding suggested alternatives.

Preparing a dosing card containing only the most essential elements of the patient’s medications can be highly beneficial. Including the name of the pill, an image (if possible), the condition it is for, and time of day taken can be extremely helpful for patients who take many medications or who have cognitive barriers.

Reminder calls, texts, or e-mails are helpful for many patients, especially those with busy lifestyles. Automatic refills are a useful strategy. Small details, like splitting a patient’s pills when necessary and providing easy-off caps, can be beneficial.

Whatever the barriers to adherence may be, the only way to assess them is to talk to the patient. The pharmacist needs to be diligent about including the patient in the treatment experience. The more trust the patient has in the pharmacist, the more he or she will open up and disclose any apprehensions or difficulties about taking his or her medication. Only then can the pharmacist play an integral role in improving a patient’s adherence.


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