title: A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; ≤4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant alone.
  
  
  METHODS
  In this multicenter, 9-week, double-blind, placebo-controlled, dose-optimization study, subjects (N = 461) continued their stable dose of psychostimulant given in the morning and were randomized to receive GXR in the morning (GXR AM), GXR in the evening (GXR PM), or placebo. Efficacy measures included ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events (AEs), vital signs, electrocardiograms, and laboratory evaluations.
  
  
  RESULTS
  At endpoint, GXR treatment groups showed significantly greater improvement from baseline ADHD-RS-IV total scores compared with placebo plus psychostimulant (GXR AM, p = .002; GXR PM, p < .001). Significant benefits of GXR treatment versus placebo plus psychostimulant were observed on the CGI-S (GXR AM, p = .013; GXR PM, p < .001) and CGI-I (GXR AM, p = .024; GXR PM, p = .003). At endpoint, small mean decreases in pulse, systolic, and diastolic blood pressure were observed in GXR treatment groups versus placebo plus psychostimulant. No new safety signals emerged following administration of GXR with psychostimulants versus psychostimulants alone. Most AEs were mild to moderate in severity.
  
  
  CONCLUSIONS
  Morning or evening GXR administered adjunctively to a psychostimulant showed significantly greater improvement over placebo plus psychostimulant in ADHD symptoms and generated no new safety signals. Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://www.clinicaltrials.gov; NCT00734578.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. twilens@partners.org
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Wilens
authors.forename: Oscar
authors.initials: O
authors.lastname: Bukstein
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Ann
authors.initials: A
authors.lastname: Childress
authors.forename: Thomas
authors.initials: T
authors.lastname: Rugino
authors.forename: Andrew
authors.initials: A
authors.lastname: Lyne
authors.forename: Kara
authors.initials: K
authors.lastname: Grannis
authors.forename: Sharon
authors.initials: S
authors.lastname: Youcha
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / 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* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000316:Adrenergic alpha-Agonists; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D010919:Placebos; D016316:Guanfacine