Medication Adherence

Failure on the part of a patient to take all doses of medication exactly as prescribed is one of the most common therapeutic misadventures. Nonadherence is typically defined as taking less than 80% of prescribed doses of a medication, although it may also include taking too many doses. In actual clinical practice, by this definition, rates of nonadherence average about 50%—much higher than in the randomized clinical trials required for approval of the same drugs.1–4 This adherence gap represents an important potential therapeutic opportunity, as the clinical consequences of varying degrees of nonadherence are often poorly understood but frequently detrimental to the patient.5–10 To understand medication adherence prescribers must be aware of the many factors influencing it, an awareness that goes well beyond the prescriber’s gestalt of the patient’s ability to remember to take a medicine. A conscientious prescriber evaluates the patients’ beliefs about the efficacy, affordability, and adverse effects of the medications they are prescribing; the presence of medical comorbidities including psychiatric and substance use disorders that can affect drug taking; structural factors such as out-of-pocket drug costs, accessibility to health service resources, and the social and cultural context in which a patient’s treatment occurs.11–15 All are important approaches to determining a patient’s risk for nonadherence, although none is completely predictive. The ability to objectively measure adherence is often limited. Drug concentration monitoring (also known as therapeutic drug monitoring; TDM) is a direct and objective measurement of adherence but is available for only a small number of drugs and often reflects drugtaking behavior over a short preceding term. For drugs whose plasma half-life is short, the value of TDM as a measure of adherence is extremely limited.16 Adherence can be assessed indirectly through objective measures of disease activity, such as blood pressure, hemoglobin A1C, or HIV plasma virus RNA concentration (viral load). Such measures are sensitive but not specific indicators of adherence, as they can be affected by a number of factors in addition to drug-taking behavior.5,17 Patient self-reporting remains the most convenient and frequently used mode of adherence assessment. Although patients often overestimate their own adherence, self-assessment is often as effective as more sophisticated methods.17–20 Pill counts are a feasible and effective adjunct to self-reporting but can be perceived as obtrusive by the patient and may promote dose dumping.17 Tracking pharmacy refill records is an effective and unobtrusive alternative that tends to have both positive and negative predictive value for assessing adherence but requires ready access to all pharmacies the patient might be using.21 These methods assume the patient is actually consuming the medication and is not sharing it with others. Once nonadherence is identified, what can be done about it? The initial and most critical step is a thorough investigation into the underlying factors contributing to each patient’s unique nonadherent behavior pattern. Careful communication between the patient and the prescriber about the medication’s purpose, administration instructions, and common side effects is an important second step.22,23 Additional strategies shown to improve adherence include reducing dosing frequencies and pill burden through long-acting and combination formulations, recruiting allied health professionals to provide support, education, and counseling interventions, and enhancing patient communication and engagement through technologies such as text messaging,