title: Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder.
abstract: OBJECTIVE
  A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactivity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously.
  
  
  METHODS
  In this 9-week, double-blind, active-controlled study, patients aged 6-17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients <70 kg: 0.5-1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients ≥70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (≥25, ≥30 or ≥50 %) or a Clinical Global Impressions (CGI)-Improvement (CGI-I) score of 1 or 2 throughout weeks 4-9. CGI-Severity (CGI-S) scores were also assessed, as an indicator of remission.
  
  
  RESULTS
  A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p < 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also significantly (p < 0.05) higher among LDX-treated patients (ADHD-RS-IV ≥25, 66.1 %; ADHD-RS-IV ≥30, 61.4 %; ADHD-RS-IV ≥50, 41.7 %; CGI-I, 52.0 %) than among ATX-treated individuals (ADHD-RS-IV ≥25, 51.1 %; ADHD-RS-IV ≥30, 47.4 %; ADHD-RS-IV ≥50, 23.7 %; CGI-I, 39.3 %). Finally, by week 9, 60.7 % of patients receiving LDX and 46.3 % of those receiving ATX had a CGI-S score of 1 (normal, not at all ill) or 2 (borderline mentally ill), and greater proportions of patients in the LDX group than the ATX group experienced a reduction from baseline of at least one CGI-S category.
  
  
  CONCLUSIONS
  Both LDX and ATX treatment were associated with high levels of treatment response in children and adolescents with ADHD and a previous inadequate response to MPH. However, within the parameters of the study, LDX was associated with significantly higher treatment response rates than ATX across all response criteria examined. In addition, higher proportions of patients in the LDX group than the ATX group had a CGI-S score of 1 or 2 by week 9, indicating remission of symptoms. Both treatments were generally well tolerated, with safety profiles consistent with those observed in previous studies.
authors.affiliation: Paediatric Psychopharmacology, Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, PO Box 12 21 20, 68072, Mannheim, Germany, ralf.dittmann@zi-mannheim.de.
authors.forename: Ralf W
authors.initials: RW
authors.lastname: Dittmann
authors.forename: Esther
authors.initials: E
authors.lastname: Cardo
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Anderson
authors.forename: Ben
authors.initials: B
authors.lastname: Adeyi
authors.forename: Beatriz
authors.initials: B
authors.lastname: Caballero
authors.forename: Paul
authors.initials: P
authors.lastname: Hodgkins
authors.forename: Richard
authors.initials: R
authors.lastname: Civil
authors.forename: David R
authors.initials: DR
authors.lastname: Coghill
mesh_terms: D000293:Adolescent; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine