title: Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder.
abstract: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD.
  
  
  
  The sample comprised 179 participants aged 7 to 14 years old with ADHD (113 boys, 55 girls). Participants were randomized to 1 of 3 blinded conditions: guanfacine (GUAN), d-methylphenidate (DMPH), or the combination (COMB). Electroencephalography (EEG) was performed pre-, mid-, and post-medication titration, with concomitant assessment of behavioral and cognitive functioning.
  
  
  
  Analyses of spectral power measures during resting EEG suggested that each medication condition displayed a distinct profile of effects on cortical activity. Significant time effects suggested that GUAN decreased global alpha band (8-12 hertz [Hz]) power, DMPH and COMB increased centro-parietal beta band (13-21 Hz) power, and COMB resulted in decreased theta band (4-7 Hz) power. Relative to other medication groups, COMB was associated with significantly lower theta band power and DMPH with higher beta band power compared with those in the GUAN group. Medication-related changes in theta power were correlated with improvements in behavioral and cognitive functioning.
  
  
  
  These data reveal distinct underlying medication-related effects on neural mechanisms. The COMB condition uniquely exhibited an EEG profile that was associated with improved behavioral and cognitive functioning. Clinical trial registration information-Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles. Electronic address: sloo@mednet.ucla.edu.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Loo
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bilder
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Cho
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sturm
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cowen
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Patricia
authors.initials: P
authors.lastname: Walshaw
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Levitt
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: Melissa
authors.initials: M
authors.lastname: Del'Homme
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: John
authors.initials: J
authors.lastname: Piacentini
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
authors.forename: James J
authors.initials: JJ
authors.lastname: McGough
authors.affiliation: University of California, Los Angeles Semel Institute, Los Angeles.
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 / Q000188:drug therapy* / Q000503:physiopathology*; D058256:Brain Waves / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D016316:Guanfacine
keywords: children; electroencephalography; medication; stimulants; treatment