Abstract
BACKGROUND: Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients' symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD. OBJECTIVE: The aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively. METHODS: Patients (aged 6-17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants' parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome. RESULTS: The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p < 0.001) in Achievement, 1.079 (p < 0.001) in Risk Avoidance, 0.421 (p < 0.01) in Resilience and 0.365 (p < 0.05) in Satisfaction. In LDX-treated patients, placebo-adjusted improvements from baseline to endpoint in WFIRS-P scores were statistically significant (p < 0.001) for total score and four of the six domains, with effect sizes of 0.924 (total score), 1.249 (Learning and School), 0.730 (Family), 0.643 (Social Activities) and 0.640 (Risky Activities). OROS-MPH treatment showed similar patterns of improvement from baseline to endpoint in both CHIP-CE:PRF and WFIRS-P scores. CONCLUSIONS: Baseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.