title: Health-related quality of life and functional outcomes from a randomized, controlled study of lisdexamfetamine dimesylate in children and adolescents with attention deficit hyperactivity disorder.
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.
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, P.O. Box: 12 21 20, D-68072, Mannheim, Germany, tobias.banaschewski@zi-mannheim.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: César
authors.initials: C
authors.lastname: Soutullo
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.forename: Mats
authors.initials: M
authors.lastname: Johnson
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zuddas
authors.forename: Paul
authors.initials: P
authors.lastname: Hodgkins
authors.forename: Ben
authors.initials: B
authors.lastname: Adeyi
authors.forename: Liza A
authors.initials: LA
authors.lastname: Squires
authors.forename: David
authors.initials: D
authors.lastname: Coghill
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004522:Educational Status; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
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