Adherence to ADHD medication is often suboptimal, which can negatively affect treatment outcomes.1,2 Patients and their families may think that the medication has less than optimal effectiveness and is associated with intolerable adverse effects, which may contribute to poor adherence.3
How important is compliance? | Professor Peter Hill | Independent Child and Adolescent Psychiatrist, London, UK
A 2016 review by Frank et al identified 41 studies that reported reasons for patient non-adherence to ADHD medication. All studies were published from 1997–2014 and examined ADHD medication adherence over the long term (>1 year) in children, adolescents or adults.4
Commonly reported reasons for poor adherence to ADHD medication included:4
- Own wish/remission/don’t need (19.9%)
- Withdrew consent (16.2%)
- Adverse effects (15.1%)
- Suboptimal effect (14.6%).
The reasons why children and adolescents stop and restart ADHD medication were also investigated here, using the prospective longitudinal cohort from the Multimodal Treatment of ADHD study in children with ADHD. At the 12-year follow-up, 372 participants (mean age 21.7 years) reported ever taking ADHD medication, and 286 (77%) reported stopping medication for ≥1 month at some time during childhood or adolescence (mean age 13.3 years).5
The most common reasons for stopping medication related to:5
- Medication not needed/helping
- Adverse effects
- Logistical barriers of getting or taking medication
- Social concerns or stigma.
After stopping medication for ≥1 month, 64 (17%) participants reported restarting medication, which was commonly due to the medication being needed or it being helpful, and the logistical barriers to getting or taking the medication were resolved. Parent involvement in decisions to stop or restart medication decreased with age, suggesting that tailored strategies may help engage adolescents as full partners in their treatment plan.5
In another study, results from an online questionnaire found that in adolescents who had filled ≥2 prescriptions for ADHD medication (n=181; aged 12–18 years), 51% experienced side effects from their medication and 83% of participants had an indifferent attitude toward their ADHD medication. More than half of the participants reported non-adherence (61%), despite many thinking their medication was effective.6
Conversely, in a different study, of the 101 adolescents on long-term medication prescription for ≥6 months, adherence was high (mean value of 88% on the Medication Adherence Report Scale [MARS]). Adolescents who had more belief in the necessity of medication and less concerns about side effects, or who experienced less side effects, were also more likely to be adherent.7
A range of different treatment formulations are available to clinicians, for example:
- Methylphenidate is available in immediate- and extended-release formulations.8-15
- Dexamfetamine is administered as tablets in a single dose or as an oral solution.16
- Atomoxetine is administered as capsules once or twice daily.17
- Lisdexamfetamine dimesylate is administered as a capsule once daily.18
- Guanfacine is administered as a tablet once daily.19
Factors influencing adherence to ADHD medication
Psychoeducation and knowledge of a patient’s acceptance of their condition may be helpful in encouraging adherence to medication, particularly in adolescents.20 In support of this, adolescents’ perceptions of the degree of stigma associated with ADHD have been reported to affect receptiveness to treatment,21 and multiple daily doses of medication, involving dosing during school hours, may be a source of embarrassment for students with ADHD.1 Moreover, ADHD-related forgetfulness may also cause difficulty in adhering to a treatment plan that requires multiple daily doses; therefore, once-daily doses may be more helpful.20
Clinicians should ensure that patients are fully informed of the balance of risks and benefits of any treatment for ADHD, and should check that problems with adherence are not due to misconceptions.22 The following strategies to support adherence to treatment have been recommended by the National Institute for Health and Care Excellence:22
- Encourage patients to be responsible for their own health, including taking their medication as needed.
- Provide the patient with clear instructions about how to take their medication in picture or written format. This information may include dose, duration, adverse effects and dosage schedule.
- Advise the patient to use visual reminders to take their medication regularly (e.g. apps, alarms, clocks, pill dispensers, or notes on calendars or fridges).
- Suggest that the patient takes their medication as part of their daily routine (e.g. before meals or after brushing teeth).
- Encourage the patient and their family/carers to attend peer support groups and encourage parents/carers to oversee ADHD medication for children and adolescents.
One study in 39 children with ADHD found that patients who used a mobile app demonstrated significantly greater adherence to medication (p<0.05) and a significant improvement in Clinician Rating Scale score (p<0.05) compared with patients who were treated as usual. The mobile app not only served as a medication reminder, but facilitated communication between the patient and the treating physician.23
A Canadian study of 53 university students with ADD or ADHD (mean age at diagnosis 14.7 years) reported that participants were adjusting levels of medication adherence on a day-to-day basis, according to perceived benefits and risks.24
The participating students were surveyed on whether they took, or intended to take, all of their ADHD medication as prescribed a) last Tuesday, b) last Saturday, c) next Tuesday and d) next Saturday. The frequency of not taking ADHD medication ‘on purpose’ and ‘because of forgetting’ was also ascertained.24
Students were more likely to take medication for ADHD on weekdays than at the weekend (Figure). Adherence on weekdays was associated with the belief that ADHD medication enhances academic performance and social skills, whereas weekend adherence was influenced by perceived loss of authentic self and negative side effects.24
Figure: Adherence rates in university students with ADHD (n=53). Reproduced with kind permission from Gould ON et al. J Atten Disord 2016; 22: 349-355.24
Data from a Turkish study of 102 adults (aged >18 years) with ADHD found that adherence to ADHD medication was positively associated with a university education (p=0.05) and referral for family history of ADHD (p=0.03).25
Adherence to different ADHD medications
The German Treatment Compliance in Children and Adolescents on ADHD Medication (COMPLY) study investigated rates of adherence to ADHD medication in children and adolescents (aged 6–17 years; n=504) over a 12-month period. At baseline, 247 patients were prescribed psychostimulants, 252 patients were prescribed non-stimulant medication (atomoxetine), and five patients were prescribed both types of medication concomitantly.26
Medication adherence was measured using the Pediatric Compliance Self-Rating (PCSR) instrument and items 1–4 of the MARS.26
At 12-month follow-up, medication adherence (PCSR score ≥5) was reported in:26
- 74.2% of the psychostimulant group
- 67.5% of the atomoxetine group.
Mean MARS score declined in both treatment groups:26
- From 3.6 to 3.1 in the psychostimulant group
- From 3.7 to 2.9 in the atomoxetine group.
Overall, there were no significant differences in adherence between patients taking atomoxetine and patients taking psychostimulant medication.26
An analysis of South Korean insurance claims data (2009–2013) assessed the adherence of children and adolescents (aged 6–18 years; n=10,343) to four different ADHD medications.27
Using a medication possession ratio cut-off of ≥80%, adherence was achieved in:27
- 27.5% of patients taking immediate-release methylphenidate
- 30.5% of patients taking extended-release methylphenidate
- 28.1% of patients taking osmotic-controlled release oral delivery system methylphenidate
- 26.7% of patients taking atomoxetine.
Logistic regression analysis indicated no significant difference in adherence between the four available ADHD medication types.27
A retrospective, observational cohort study compared 1-year direct healthcare costs and utilisation among children and adolescents (6–17 years) with ADHD initiating the non-stimulant medication atomoxetine or extended-release guanfacine in the US.28
- Over the 1-year period, children and adolescents with ADHD used their index medication for 6–7 months on average.28
- Those who initiated extended-release guanfacine persisted for ~22 days longer than those administered monotherapy atomoxetine.28
- Compared with patients who initiated extended-release guanfacine, adherence and persistence was significantly lower in patients who initiated atomoxetine (p<0.0001).28
- Marcus SC, Wan GJ, Kemner JE, et al. Continuity of methylphenidate treatment for attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 2005; 159: 572-578.
- Barner JC, Khoza S, Oladapo A. ADHD medication use, adherence, persistence and cost among Texas Medicaid children. Curr Med Res Opin 2011; 27(Suppl 2): 13-22.
- Charach A, Fernandez R. Enhancing ADHD medication adherence: challenges and opportunities. Curr Psychiatry Rep 2013; 15: 371.
- Frank E, Ozon C, Nair V, et al. Examining why patients with attention-deficit/hyperactivity disorder lack adherence to medication over the long term: a review and analysis. J Clin Psychiatry 2015; 76: e1459-e1468.
- Brinkman WB, Simon JO, Epstein JN. Reasons why children and adolescents with attention-deficit/hyperactivity disorder stop and restart taking medicine. Acad Pediatr 2018; 18: 273-280.
- Kosse RC, Bouvy ML, Philbert D, et al. Attention-deficit/hyperactivity disorder medication use in adolescents: the patient’s perspective. J Adolesc Health 2017; 61: 619-625.
- Emilsson M, Gustafsson PA, Ohnstrom G, et al. Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder. Eur Child Adolesc Psychiatry 2017; 26: 559-571.
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- Canadian ADHD Resource Alliance (CADDRA). Canadian ADHD Practice Guidelines. Fourth Edition. Toronto, ON; CADDRA, 2018.
- Bussing R, Zima BT, Mason DM, et al. Receiving treatment for attention-deficit hyperactivity disorder: do the perspectives of adolescents matter? J Adolesc Health 2011; 49: 7-14.
- NICE guideline 2018. Attention deficit hyperactivity disorder: diagnosis and management. Available at: https://www.nice.org.uk/guidance/ng87. Accessed February 2019.
- Weisman O, Schonherz Y, Harel T, et al. Testing the efficacy of a smartphone application in improving medication adherence, among children with ADHD. Isr J Psychiatry Relat Sci 2018; 55: 59-63.
- Gould ON, Doucette C. Self-management of adherence to prescribed stimulants in college students with ADD/ADHD. J Atten Disord 2016; 22: 349-355.
- Semerci B, Taskiran S, Tufan E, et al. Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study. Atten Defic Hyperact Disord 2016; 8: 139-147.
- Wehmeier PM, Dittmann RW, Banaschewski T. Treatment compliance or medication adherence in children and adolescents on ADHD medication in clinical practice: results from the COMPLY observational study. Atten Defic Hyperact Disord 2015; 7: 165-174.
- Bhang SY, Hwang JW, Kwak YS, et al. Differences in utilization patterns among medications in children and adolescents with attention-deficit/hyperactivity disorder: a 36-month retrospective study using the Korean health insurance review and assessment claims database. J Korean Med Sci 2016; 31: 1284-1291.
- Molife C, Haynes VS, Nyhuis A, et al. Healthcare utilization and costs of children with attention deficit/hyperactivity disorder initiating atomoxetine versus extended-release guanfacine. Curr Med Res Opin 2018; 34: 619-632.