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

Kavita Gajria, Mei Lu, Vanja Sikirica, Peter Greven, Yichen Zhong, Paige Qin, Jipan Xie, Kavita Gajria, Mei Lu, Vanja Sikirica, Peter Greven, Yichen Zhong, Paige Qin, Jipan Xie

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.

Keywords: ADHD medication; adherence; literature review; persistence; treatment discontinuation.

Figures

Figure 1
Figure 1
PRISMA diagram of the literature selection criteria. Notes:aNonrelevant publication type: 1) nonprimary publications of the real-world studies (eg, a publication that has less data than the primary publication to report the same outcomes); 2) conference abstracts or posters; 3) Congress proceedings; 4) books/chapters/addresses/bibliographies/biographies/lectures; 5) case reports; letters; or 6) treatment guidelines for countries other than: US, Canada, UK, Germany, France, Spain, Italy, Sweden, and the Netherlands. bNonrelevant study design: preclinical studies; clinical trials; prognostic studies; genetic studies; nonpopulation-based interview studies; economic studies; reviews/meta-analyses not of real-world studies. cNonrelevant population: nonhuman subjects; not ADHD patients; <80% of the study population have ADHD as the primary disorder. dNonrelevant intervention: no drug treatment; drug treatment not of interest: stimulants (methylphenidate, amphetamine: amphetamine/dexamphetamine and lisdexamfetamine), nonstimulants (atomoxetine, guanfacine immediate/extended release, and clonidine immediate/extended release). eNonrelevant outcome: 1) does not report discontinuation/continuation results; and 2) does not report reasons for ADHD drug discontinuation. fFor expert opinions (reviews, meta-analysis, editorials/commentaries, treatment guidelines), all the relevant citations for ADHD medication adherence or discontinuation were reviewed, and original papers were screened for inclusion. Reviews and meta-analyses were included for data extraction if they reported expert opinions that were not based on original studies. gExpert opinions refer to reviews, meta-analysis, editorials/commentaries, treatment guidelines. Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ADHD, attention-deficit/hyperactivity disorder.

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