Individual Treatment Response in ADHD

Abstract and Introduction

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly complex disorder with multiple treatment options. Impairments associated with ADHD, rather than symptoms defining the disorder, are the primary reason for referral of individuals to clinical services; consequently, they should also be key targets for intervention. Impairments are moderated by factors such as comorbidities, family environment and intelligence quotient, and particular challenges may vary between patients. The understanding of patient and family treatment preferences, as well as identification of treatment needs and goals, should drive future clinical practice. This review addresses the assessment of ADHD treatment goals and outcomes in clinical practice, and discusses changes in future clinical research studies necessary to progress the utilization of an individualized medicine approach in ADHD.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by core symptoms of inattention, hyperactivity and impulsivity.^[1] ADHD has a worldwide prevalence of 5–7% in children and adolescents and 5% in adults, with no significant country effect observed after controlling for differences in diagnostic algorithms used to define the disorder.^[2,3] Three subtypes of ADHD (predominantly inattentive, predominantly hyperactive–impulsive and combined type) are defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).^[1] A recent meta-analysis reported that the predominantly inattentive subtype is most common; however, individuals with the combined subtype are most likely to be referred for clinical services^[2] and to be studied in clinical trials for drug approvals. A fifth edition of the DSM (DSM-V) is scheduled for release in May 2013 with changes in the diagnostic criteria for ADHD proposed; for example, an increase in the threshold age of symptom onset from 7 to 12 years of age, and reduction of the number of symptoms required for diagnosis of adult ADHD.^[4]

Clear evidence that ADHD symptoms lead to clinically significant impairment in social, academic or occupational functioning in multiple settings is required for the diagnosis of the disorder, although diagnostic criteria provide little guidance on their measurement.^[1,5] If the symptoms of ADHD (e.g., difficulty sustaining attention in tasks, distractibility, fidgeting, restlessness and difficulty awaiting their turn) are defined as the behavioral expressions associated with the disorder, impairments can be conceived as the sequelae of these behaviors.^[6] Impairments in children and adolescents with ADHD are observed in social, emotional, familial, academic and behavioral functioning, and can lead to reduced health-related quality of life (HRQoL), not only for the patient, but also for their family.^[7–10] HRQoL is a subjective measure of how a patient feels, a patient's own perception of the impact of a disorder and its treatment on physical, psychological and social functioning, daily life and wellbeing.^[101] While patients may develop strategies to cope with ADHD as they transition into adulthood, and some childhood symptoms may attenuate with age, ADHD and associated impairments may persist and have a negative impact on multiple domains of life. Adults with childhood ADHD have lower academic and occupational attainment compared with their non-ADHD peers, leading to a relative economic disadvantage.^[11,12] In the USA, income losses and decreased work productivity are the largest contributors to the economic burden associated with adult ADHD, accounting for approximately three quarters of associated costs.^[13] Relationship and social problems, including increased risk of antisocial and substance-use disorders, and an association between ADHD and negative life events, are further contributors to reduced HRQoL in affected adults.^{[11,12,14–16]} The accumulative negative impact of symptoms and impairments associated with ADHD extends into older age and has been demonstrated in adults aged 60–77 years.^[17]

Sidebar

Key Issues

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by core symptoms of inattention, hyperactivity and impulsivity. For diagnosis of the disorder, clear evidence that symptoms lead to clinically significant impairment in social, academic or occupational functioning is required in multiple settings.
There is general agreement among ADHD treatment guidelines for a multimodal approach of pharmacologic treatment in combination with psychosocial/psychotherapeutic interventions to address symptoms and impairments associated with the disorder.
Impairments associated with ADHD such as difficulties in family functioning, peer relationships and academic functioning are typically the basis of referral to clinical services and should be key targets for intervention. Impairments are modified by external factors such as comorbidities, family environment and intelligence quotient, creating a highly complex disorder environment with multiple targets for treatment consideration.
Specific treatment goals may vary between patients and families depending on individual circumstances. Assessment of individual deficits and understanding of patient and/or parent/caregiver individual preferences are central to individualized medicine, and for optimal monitoring of progress and outcome.
Evaluation of functional impairment and health-related quality of life, in addition to ADHD symptoms, can further differentiate between the individual treatment needs and goals of patients. There remain, however, many symptom, impairment and health-related quality of life outcomes beyond the currently available instruments for which the impact of the disorder or the benefits of treatment are not fully understood.
In order to implement an individualized medicine approach, research and findings targeted to specific patient populations and generalizable to clinical practice are required. Key to this will be the development of psychometrically validated instruments to measure treatment response beyond core symptoms and the understanding of patient characteristics, preferences, beliefs and behaviors that lead to different outcomes.
To date, there is a lack of conclusive evidence for predictors of treatment response in patients with ADHD; however, initial research findings are encouraging.
Measuring individual treatment response in a regulatory approval setting will be challenging, but innovative trial designs show promise for the future.