Kelly I. Kamimura-Nishimura, MD, MS Assistant Professor Department of Pediatrics Division of Developmental and Behavioral Pediatrics
William B. Brinkman, MD, MEd, MSc Professor Department of Pediatrics Division of General and Community Pediatrics
Tanya E. Froehlich, MD, MS Associate Professor Department of Pediatrics Division of Developmental and Behavioral Pediatrics
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Cincinnati Children’s Hospital Medical Center University of Cincinnati Cincinnati, Ohio
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Supported by the National Institute of Mental Health R01 MH105425 (T.F.), R01 MH105425-S1 (T.F.), and K23 MH083027 (W.B.).
To maximize outcomes, understand and address the factors that affect adherence.
Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, affecting 8% to 12% of school-aged children in the United States1-3 with significant impairments that often persist into adulthood.4-8 Current guidelines recommend stimulant medication and/or behavioral therapies as first-line treatments for ADHD.9,10 There is a wealth of evidence on the efficacy of stimulants in ADHD, with the most significant effects noted on core ADHD symptoms.11,12 Additional evidence links stimulants to decreased long-term negative outcomes, including reduced school absences and grade retention,13 as well as modestly but significantly improved reading and math scores.14 Other studies have reported that individuals with ADHD who receive medication have decreased criminality,15,16 motor vehicle accidents,17,18 injuries,19 substance abuse,20-22 and risk for subsequent and concurrent depression.23 Therefore, the evidence suggests that consistent medication treatment helps improve outcomes for individuals with ADHD.
Adherence is defined as “the extent to which a person’s behavior (eg, taking medication) corresponds with agreed recommendations from a clinician.”24 Unfortunately, pediatric ADHD medication adherence has been found to be poor (approximately 64%).25-30 Nonadherence to ADHD medication has been linked to multiple factors, including caregiver/family and child/adolescent factors(Table 1), medication-related factors (Table 2), and health care/system factors (Table 3). Understanding and addressing these factors is essential to maximizing long-term outcomes. In this article, we review the factors associated with nonadherence to ADHD medication, and outline strategies to improve adherence.
Caregiver/family characteristics
Caregiver beliefs about ADHD and their attitudes toward treatment have been associated with the initiation of and adherence to ADHD medication. For example, caregivers who view a child’s difficulties as a medical disorder that requires a biologic intervention are more likely to accept and adhere to medication.31 Similarly, caregivers who perceive ADHD medication as safe, effective, and socially acceptable are more likely to be treatment-adherent.32-35Other caregiver-related factors associated with improved ADHD medication adherence include:
increased caregiver knowledge about ADHD33
receiving an ADHD diagnosis based on a thorough diagnostic process (ie, comprehensive psychological testing)36
satisfaction with information about medicine
comfort with the treatment plan.34
Socioeconomic status, family functioning, and caregiver mental health diagnoses (eg, ADHD, depression) have also been linked to ADHD medication adherence. Several studies, including the Multimodal Treatment Study of Children with ADHD,11 a landmark study of stimulant medication for children with ADHD, have found an association between low income and decreased likelihood of receiving ADHD medication.2,37-39 Further, Gau et al40 found that negative caregiver-child relationships and family dysfunction were associated with poor medication adherence in children with ADHD.9 Prior studies have also shown that mothers of children with ADHD are more likely to have depression and/or anxiety,41,42 and that caregivers with a history of mental health diagnoses are more accepting of initiating medication treatment for their children.43 However, additional studies have found that caregiver mental health diagnoses decreased the likelihood of ADHD medication adherence.40,44
Child characteristics
Child characteristics associated with decreased ADHD medication adherence include older age (eg, adolescents vs school-aged children),29,30,34,40,45-47 non-White race, Hispanic ethnicity,29,33,48-51 female gender,29,33,52 lower baseline ADHD symptom severity,30,37 and child unwillingness to take medications.34 However, prior studies have not been completely consistent about the relationship between child comorbid conditions (eg, oppositional defiant disorder [ODD], conduct disorder) and ADHD medication adherence. A few studies found that child comorbid conditions, especially ODD, mediate poorADHD medication adherence, possibly secondary to an increased caregiver-child conflict.30,53,54 However, other studies have reported that the presence of comorbid ODD, depression, and anxiety predicted increasedadherence to ADHD medications.37,46
Medication-related factors
Adverse effects of medications are the most commonly cited reason for ADHD medication nonadherence.5,33,54-56 The adverse effects most often linked to nonadherence are reduced weight/appetite, increased aggressive behavior/irritability, and sleep difficulties.54,57 Studies comparing methylphenidates and amphetamines, including 2 recent meta-analyses, suggest that amphetamines may be less well-tolerated on average, particularly with regard to emotional lability and irritability.45,58,59 Therefore, clinicians might consider using methylphenidate-based preparations as first-line psychopharmacologic interventions in children with ADHD, as is consistent with the findings and conclusions drawn by a recent systematic review and meta-analysis of the comparative efficacy and tolerability of ADHD medications.60
On the other hand, increased ADHD medication effectiveness has been associated with improved medication adherence.5,34,54-56 Medication titration and dosing factors have also been shown to affect adherence. Specifically, adherence has been improved when ADHD medications are titrated in a systematic manner soon after starting treatment, and when families have an early first contact with a physician after starting medication (within 3 months).28 In addition, use of a simplified dose regimen has been linked to better adherence: patients who are prescribed long-acting stimulants are more likely to adhere to treatment compared with patients who take short-acting formulations.26,40,49,61-63 It is possible that long-acting stimulants increase adherence because they produce more even and sustained effects on ADHD symptoms throughout the day, compared with short-acting formulations.64 Furthermore, the inconvenience of taking multiple doses throughout the day, as well as the potential social stigma of mid-school day dosing, may negatively impact adherence to short-acting formulations.10