title: Guanfacine extended release adjunctive to a psychostimulant in the treatment of comorbid oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  The purpose of this study was to assess the effect of guanfacine extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  A multicenter, double-blind, placebo-controlled dose-optimization study of GXR (1-4 mg/d) or placebo administered morning (a.m.) or evening (p.m.) adjunctive to psychostimulant was conducted in subjects ages 6-17 with suboptimal response to psychostimulant alone. Suboptimal response was defined as treatment with a stable dose of psychostimulant for ≥4 weeks with ADHD Rating Scale IV total score ≥24 and Clinical Global Impressions-Severity of Illness score ≥3, as well as investigator opinion. Primary efficacy and safety results have been reported previously. Secondary efficacy measures included the oppositional subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L); these are reported herein.
  
  
  RESULTS
  Significant reductions from baseline to the final on-treatment assessment on the oppositional subscale of the CPRS-R:L were seen with GXR plus psychostimulant compared with placebo plus psychostimulant, both in the overall study population (placebo-adjusted least squares [LS] mean change from baseline to the final on-treatment assessment: GXR a.m.+psychostimulant, -2.4, p=0.001; GXR p.m.+psychostimulant, -2.2, p=0.003) as well as in the subgroup of subjects with significant baseline oppositional symptoms (GXR a.m.+psychostimulant, -3.6, p=0.001; GXR p.m.+psychostimulant, -2.7, p=0.013). Treatment-emergent adverse events were reported by 77.3%, 76.3%, and 63.4% of subjects in the GXR a.m., GXR p.m., and placebo groups, respectively, in the overall study population.
  
  
  CONCLUSIONS
  GXR adjunctive to a psychostimulant significantly reduced oppositional symptoms compared with placebo plus a psychostimulant in subjects with ADHD and a suboptimal response to psychostimulant alone.
authors.affiliation: 1 Department of Psychiatry, Johns Hopkins University and the Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Keith
authors.initials: K
authors.lastname: McBurnett
authors.forename: Carla
authors.initials: C
authors.lastname: White
authors.forename: Sharon
authors.initials: S
authors.lastname: Youcha
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D016316:Guanfacine