Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder – a systematic literature review

Abstract

Untreated attention-deficit/hyperactivity disorder (ADHD) can lead to substantial adverse social, economic, and emotional outcomes for patients. The effectiveness of current pharmacologic treatments is often reduced, due to low treatment adherence and medication discontinuation. This current systematic literature review analyzes the current state of knowledge surrounding ADHD medication discontinuation, focusing on: 1) the extent of patient persistence; 2) adherence; and 3) the underlying reasons for patients’ treatment discontinuation and how discontinuation rates and reasons vary across patient subgroups. We selected 91 original studies (67 with persistence/discontinuation results, 26 with adherence results, and 41 with reasons for discontinuation, switching, or nonadherence) and 36 expert opinion reviews on ADHD medication discontinuation, published from 1990 to 2013. Treatment persistence on stimulants, measured by treatment duration during the 12-month follow-up periods, averaged 136 days for children and adolescents and 230 days for adults. Owing to substantial study heterogeneity, comparisons across age or medication type subgroups were generally inconclusive; however, long-acting formulations and amphetamines were associated with longer treatment duration than short-acting formulations and methylphenidates. The medication possession ratio, used to measure adherence, was <0.7 for all age groups and medication classes during a 12-month period. Adverse effects were the most commonly cited reason for discontinuation in all studies. Original research studies reported the lack of symptom control as a common discontinuation reason, followed by dosing inconvenience, social stigma associated with ADHD medication, and the patient’s attitude. In summary, although there was a lack of consistency in the measurement of adherence and persistence, these findings indicate that drug adherence and persistence are generally poor among patients with ADHD. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers and patients on treatment goals, administering long-acting medications, and following-up with patients to verify if medication is still effective and well-tolerated.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

“…Under these real-world conditions, ~70% of patients completed the 1-year study phase without discontinuing pharmacological treatment: 128 patients continued to receive MPH, 25 had switched to dextroamphetamine, and 10 had switched to atomoxetine. In line with randomized, controlled clinical trials, AEs and lack of efficacy were reported as the most common reasons for treatment discontinuation 59,60. Moreover, the study revealed that approximately half of the patients preferred immediate-release MPH over extended-release formulations, highlighting the need for clinicians to consider alternative MPH formulations on an individual patient basis.…”

“…Buitelaar et al evaluated the long-term efficacy and tolerance of OROS-MPH, wherein no evidence of withdrawal or rebound was reported after treatment discontinuation 64. As previously reported in randomized controlled trials, the most common reason reported for treatment discontinuation was AE 60. Ginsberg et al reported a lower rate (2.3%) of AE-induced discontinuation during the extension phase of the MPH-LA study compared with other open-label extension studies such as OROS-MPH (18.5%) 55,63.…”

Factors that Affect the Adherence to ADHD Medications during a Treatment Continuation Period in Children and Adolescents: A Nationwide Retrospective Cohort Study Using Korean Health Insurance Data from 2007 to 2011

“…Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood disorder in psychiatric outpatient clinics, and it affects approximately 5.3% of the school aged population 1. ADHD has been regarded as a chronic condition that may continue through adulthood.…”

Stimulant Medications and Cognition, Behavior and Quality of Life in Children and Youth with HIV

“…For example, children in the PG may have performed more poorly than those in the CG because they were not adherent to their stimulant treatment regimens, a possibility consistent with recent literature on medical treatment of children and adults with ADHD. 41 Follow-up intervals were linked to children's ages and dates of enrollment into P219C, not to medication start and stop dates, and there was wide variability in treatment duration, with some participants continuing their first prescription for as little as one month. Such variability limits the interpretation of study findings.…”