title: Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study.
abstract: Extended-release guanfacine hydrochloride (GXR), a selective α2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD.
  
  
  
  Children/adolescents (6-17 years) with ADHD received open-label GXR (1-7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (≥50% increase in ADHD Rating Scale version IV total score and ≥2-point increase in Clinical Global Impression-Severity compared with RWP baseline, at two consecutive visits). The key secondary endpoint was time to treatment failure (TTF).
  
  
  
  ClinicalTrials.gov identifier NCT01081145; EudraCT 2009-018161-12.
  
  
  
  A total of 528 participants enrolled; 316 (59.8%) entered the RWP. Treatment failure occurred in 49.3% of the GXR and 64.9% of the placebo group (p = 0.006). TTF was significantly longer in GXR versus placebo (p = 0.003). GXR was well tolerated.
  
  
  
  Guanfacine hydrochloride demonstrated long-term maintenance of efficacy compared with placebo in children/adolescents with ADHD. Implications of the placebo substitution design and findings with different ADHD medications are discussed.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
authors.affiliation: Ryegate Children's Centre, Sheffield NHS Foundation Trust, Sheffield, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Harpin
authors.affiliation: Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lyne
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
authors.affiliation: Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, CIBERSAM, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep Antoni
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.affiliation: Center for Pediatric Excellence, Ottawa, ON, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: van Stralen
authors.affiliation: Centre Hospitalier de Rouffach, Rouffach, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Dutray
authors.affiliation: Shire, Eysins, Switzerland.
authors.forename: Sasha
authors.initials: S
authors.lastname: Sreckovic
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Bloomfield
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D017211:Treatment Failure
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D016316:Guanfacine
keywords: Long term; attention-deficit/hyperactivity disorder; efficacy; guanfacine; randomised; withdrawal