title: Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD.
abstract: OBJECTIVE
  To assess the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) combined with stimulants (ie, methylphenidate or amphetamine) for attention-deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  In this phase 3, double-blind, placebo-controlled trial, children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were randomized to receive CLON-XR or placebo in combination with their baseline stimulant medication. Predefined efficacy measures evaluated change from baseline to week 5. Safety was assessed by spontaneously reported adverse events, vital signs, electrocardiogram recordings, and clinical laboratory values. Improvement from baseline for all efficacy measures was evaluated using analysis of covariance.
  
  
  RESULTS
  Of 198 patients randomized, 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant. At week 5, greater improvement from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (95% confidence interval: -7.83 to -1.13; P = .009), ADHD-RS-IV hyperactivity and inattention subscale scores (P = .014 and P = .017, respectively), Conners' Parent Rating Scale scores (P < .062), Clinical Global Impression of Severity (P = .021), Clinical Global Impression of Improvement (P = .006), and Parent Global Assessment (P = .001) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group. Adverse events and changes in vital signs in the CLON-XR group were generally mild.
  
  
  CONCLUSIONS
  The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA. kolli001@mc.duke.edu
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jain
authors.forename: Matthew
authors.initials: M
authors.lastname: Brams
authors.forename: Scott
authors.initials: S
authors.lastname: Segal
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Wigal
authors.forename: Moise
authors.initials: M
authors.lastname: Khayrallah
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage; D000661:Amphetamine / Q000008:administration & dosage; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; D000661:Amphetamine; D003000:Clonidine