title: Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  To determine whether treatment with guanfacine extended release (GXR) in subjects with attention-deficit/hyperactivity disorder (ADHD) disrupted psychomotor functioning and alertness, or impacted daytime sleepiness.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-optimization, noninferiority, laboratory classroom study of GXR (1, 2, and 3 mg/day) in 182 subjects aged 6 to 17 years with ADHD. Psychomotor functioning and alertness were assessed through several measures, including the Choice Reaction Time (CRT) test from the Cambridge Neuropsychological Test Automated Battery. Sedative effects were examined via spontaneously reported adverse events of sedation, somnolence, and hypersomnia as well as fatigue and lethargy, and with two validated subject- and observer-rated sleepiness scales. Standard efficacy measures for ADHD also were included. Cardiovascular and laboratory parameters were assessed.
  
  
  RESULTS
  There were no significant differences between the GXR and placebo groups on measures of psychomotor functioning or alertness from the CRT at endpoint (least-square mean difference: 2.5 [95% confidence interval (CI): -22.9, 28.0], p = 0.8 for CRT; 2.5 [95% CI: -21.5, 26.4], p = 0.84 for correct responses; 15.5 [95% CI: -45.1, 14.1], p = 0.30 for movement time; and -8.2 [95% CI: -54.1, 37.6] p = 0.72 for total time). Most sedative adverse events were mild to moderate, occurred during dose titration, decreased with dose maintenance, and resolved during the study period. One subject in the GXR group discontinued due to fatigue and somnolence. GXR was not associated with increased daytime sleepiness. GXR treatment was associated with significant improvement in ADHD symptoms (6.3 [95% CI: 2.7, 9.8], p = 0.001 for ADHD Rating Scale IV total scores at endpoint).
  
  
  CONCLUSIONS
  At doses that resulted in significant improvement in ADHD symptoms, impairment on cognitive tasks was not observed. Daytime sleepiness did not differ with GXR compared with placebo. Results suggest that the beneficial effects of GXR on ADHD symptoms are independent of sedation.
authors.affiliation: Duke ADHD Program, Duke University Medical Center, Durham, North Carolina 27705, USA. kolli001@mc.duke.edu
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.forename: Frank A
authors.initials: FA
authors.lastname: López
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Vince
authors.forename: John M
authors.initials: JM
authors.lastname: Turnbow
authors.forename: Kimberly
authors.initials: K
authors.lastname: Farrand
authors.forename: Andrew
authors.initials: A
authors.lastname: Lyne
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Wigal
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D003692:Delayed-Action Preparations; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D010919:Placebos; D016316:Guanfacine