Attention-Deficit/Hyperactivity Disorder

An Update on Medication Adherence and Persistence in Children, Adolescents and Adults

Rana Ahmed; Parisa Aslani


Expert Rev Pharmacoeconomics Outcomes Res. 2013;13(6):791-815. 

In This Article

Adherence & Persistence


Adherence is a multi-faceted construct which at the core level is founded upon a patient's understanding of the severity of their illness, their belief in the efficacy of a chosen intervention and in their ability to control their symptoms using this intervention.[53] While differences exist in how adherence is defined between studies, the term is generally understood to reflect the extent to which a patient's actions correspond with the agreed recommendations of healthcare providers (HCPs).[54] Medication adherence more specifically, is defined as the act of conforming to HCPs' recommendations about the timing, dosage and administration frequency of the medication.[53]

Comparatively, medication persistence is a measure of treatment continuity, defined as the length of time from the initiation of therapy to its discontinuation.[53] Therefore, although these two terms are often used interchangeably in the literature it is important to recognize that they are unique and are at times two mutually exclusive constructs. Saying patients are adherent to their medication regimens does not necessarily imply that they are persistent, and the opposite is also true. To clarify, patients who purposefully skip some of their prescribed daily doses of medication would not be considered to be adherent, however they may be persistent provided that they continue treatment for the agreed period of time specified by their HCPs. In this way, it is often simpler to view adherence as whether or not patients takes their medication as prescribed for the duration of time that they are persistent with treatment.[55]


Owing to these definitional differences, adherence and persistence are measured differently, as will be demonstrated in the included studies, although both can be determined by prospective and retrospective approaches. In prospective examinations, adherence is measured over a specified period of time and reported as a percentage of the doses taken by the patient against the doses prescribed. In these studies, adherence can be determined using direct or indirect methods of measurement, each with their individual advantages and disadvantages.

Direct methods of investigation include observation of therapy and measurement of drug or metabolite concentrations in samples of a patient's saliva, urine or blood. While these approaches provide the most objective assessments of adherence, direct observation can be impractical and burdensome for clinicians in practice while the analysis of biological samples can be a costly and invasive process for patients.

Comparatively, indirect measures of adherence are generally easier to implement but may be more prone to error and distortion. These include patient or parent self-reports/questionnaires, pill counts and the use of electronic medication monitors.[8] The use of patient questionnaires is a relatively simple approach to measuring adherence however there is much controversy surrounding the accuracy and reliability of patients' reports, which often lead to an overestimation of adherence levels.[56] Pill counting which involves determining the number of pills remaining in patients' medication bottles or blister packs, may be perceived to provide a more accurate measure of adherence. However, this too is subject to distortion as patients may switch pills between medication bottles or even discard a certain amount of pills prior to clinic visits in an attempt to appear adherent.[57–59] Further, these approaches do not provide insight into the specific timing of dosages whereas the use of electronic monitoring devices such as the medication event management system (MEMS) allows such information to be obtained. These devices are increasingly becoming known as the gold standard for medication adherence measurement.[60] They generally consist of a computer chip inserted into the cap of the medication bottle which is capable of recording the dates and times that the container was opened. This information can then be downloaded from the chip directly into a computer program for analysis. While this information is useful in providing insight into the timing and frequency of medication use, it does not document whether a patient actually took the correct dose of the medication or whether it was taken at all. It is also important to note that MEMS data may be inaccurate in instances where patients remove their total daily dose (or additional doses) from the pill bottle, rather than opening the bottle on every occasion that a dose is required. Nevertheless these devices are still considered to provide the most accurate measures of adherence, although they are not routinely used in clinical practice due to their cost.

Adherence can also be determined through retrospective examinations which generally involve the study of pharmacy claims databases for information about how frequently patients refill their prescriptions. The time between the initial dispensing of the medication and when the prescription would run out without further refills is used as a proxy for adherence. The most commonly reported outcome measure in these studies is the medication or drug possession ratio (MPR/DPR) which is a reflection of the dispensed doses in relation to the dispensing period being examined.[61] The MPR is generally calculated as the total days' medication supply issued to a patient divided by the number of days the patient should have been taking the medication, which in most cases is equivalent to the number of days between prescription refills. MPR values ≥0.8 are taken to reflect adequate treatment adherence. These studies do not provide the detailed insight into patients' medication-taking behaviors provided by MEMS for example, however their strength lies in their inclusion of prescription information of thousands of patients from community settings, allowing for strong insight into real-world medication utilization.

Persistence can also be measured in both prospective and retrospective studies, although unlike adherence, it is reported as a continuous variable in terms of the number of days of continuous therapy from the point of initiation until the end of the observation period. A number of studies also report persistence as a dichotomy where patients are classified as persistent or non-persistent at the conclusion of the study period.[62] In retrospective studies, a permissible gap between consecutive refills of a prescription is pre-specified based on the specific properties and dosing regimen of the medication being examined. As long as patient records indicate that prescription refills were obtained within this 'gap', that patient is considered to be persistent.

There are, therefore, numerous approaches to conducting studies of adherence and varying definitions of the term itself. It is for this reason that a meta-analysis of the studies identified in this review was not possible. Instead, the studies have been categorized according to whether they have adopted prospective or retrospective examinations of adherence and persistence. A summary of their findings is presented in light of the definitions they have used and in comparison with those of other studies where possible.