title: Response/remission with guanfacine extended-release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  In this post hoc analysis, we assessed whether guanfacine extended-release (GXR) adjunctive to a psychostimulant resulted in greater response and remission rates than placebo + psychostimulant in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  In this 9-week, double-blind, placebo-controlled dose-optimization study, participants (N = 461) aged 6 to 17 years with suboptimal response to psychostimulants were randomized to GXR on awakening (AM) + psychostimulant, GXR at bedtime (PM) + psychostimulant, or placebo + psychostimulant.
  
  
  RESULTS
  At the final on-treatment assessment, more participants in both GXR + psychostimulant groups versus the placebo + psychostimulant group achieved response as assessed by 2 criteria: reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (1) ≥40% (GXR AM + psychostimulant = 69.8%, GXR PM + psychostimulant = 70.3%, versus placebo + psychostimulant = 57.9%; p = .032 and p = .026, respectively), or (2) ≥50% (63.1%, 64.9%, versus 43.4%; p <.001 for both). Results were similar for symptomatic remission (ADHD-RS-IV total score ≤18; 61.1%, 62.2%, versus 46.1%; p = .010 and p = .005, respectively) and syndromal remission (symptomatic remission plus Clinical Global Impressions of Severity of Illness score ≤2). The most common treatment-emergent adverse events in participants receiving GXR + psychostimulant were headache (21.2%) and somnolence (13.6%).
  
  
  CONCLUSIONS
  GXR + psychostimulant treatment resulted in a greater percentage of participants meeting stringent criteria for response and remission compared with placebo + psychostimulant. The adverse event profile of adjunctive therapy was consistent with known effects of either treatment alone. Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://clinicaltrials.gov/; NCT00734578.
authors.affiliation: Florida Clinical Research Center, LLC, Bradenton, FL and University of Florida, Gainesville, FL. Electronic address: acutler@flcrc.com.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cutler
authors.affiliation: Baylor College of Medicine, Houston.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.affiliation: DePelchin Children's Center, Houston and Baylor College of Medicine.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bukstein
authors.affiliation: Washington University School of Medicine, St. Charles, MO.
authors.forename: Gregory
authors.initials: G
authors.lastname: Mattingly
authors.affiliation: University of California, San Francisco, San Francisco.
authors.forename: Keith
authors.initials: K
authors.lastname: McBurnett
authors.affiliation: Shire Pharmaceutical Development Ltd, Basingstoke, UK.
authors.forename: Carla
authors.initials: C
authors.lastname: White
authors.affiliation: Alcobra Inc., Plymouth Meeting, PA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rubin
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000697:Central Nervous System Stimulants; D016316:Guanfacine
keywords: ADHD; guanfacine XR; remission; response; α(2A)-agonist