title: Health-related quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD.
  
  
  OBJECTIVE
  Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged 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 of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons.
  
  
  RESULTS
  The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard deviation below the normative mean in four of the five domains, and there was significant improvement across all domains from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores deteriorated in all domains in the placebo group, but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Risk Avoidance (effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction (0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the Family domain and the Learning and School domain. WFIRS-P total score and scores in all domains improved significantly from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean scores deteriorated in the placebo group but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Family, Learning and School, and Risky Activities domains and in total (effect size 0.908; p < 0.001).
  
  
  CONCLUSIONS
  Using parent-rated instruments, long-term maintenance of the beneficial effect of LDX in multiple domains of health-related quality of life and functional impairment was demonstrated by comparison of treatment continuation and withdrawal under randomized, double-blind, placebo-controlled conditions.
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, 68072, Mannheim, Germany, tobias.banaschewski@zi-mannheim.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Mats
authors.initials: M
authors.lastname: Johnson
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zuddas
authors.forename: Ben
authors.initials: B
authors.lastname: Adeyi
authors.forename: Paul
authors.initials: P
authors.lastname: Hodgkins
authors.forename: Liza A
authors.initials: LA
authors.lastname: Squires
authors.forename: David R
authors.initials: DR
authors.lastname: Coghill
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology*; D002648:Child; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D011619:Psychotropic Drugs; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine