title: Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.
abstract: Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.
  
  
  
  Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables.
  
  
  
  The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group.
  
  
  
  Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD.
  
  
  
  Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA; UCLA College of Letters and Science. Electronic address: rbilder@mednet.ucla.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bilder
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Loo
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: James J
authors.initials: JJ
authors.lastname: McGough
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Whelan
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hellemann
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA; UCLA School of Public Health.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sugar
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Del'Homme
authors.affiliation: Graduate School of Education and Information Sciences at UCLA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sturm
authors.affiliation: UCLA and the Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cowen
authors.affiliation: School of Engineering at the University of Michigan, Ann Arbor.
authors.forename: Grant
authors.initials: G
authors.lastname: Hanada
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D016316:Guanfacine
keywords: attention-deficit/hyperactivity disorder; cognition; guanfacine; stimulant; working memory