title: Shared and drug-specific effects of atomoxetine and methylphenidate on inhibitory brain dysfunction in medication-naive ADHD boys.
abstract: The stimulant methylphenidate (MPX) and the nonstimulant atomoxetine (ATX) are the most commonly prescribed medications for attention deficit hyperactivity disorder (ADHD). However, no functional magnetic resonance imaging (fMRI) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX. A randomized, double-blind, placebo-controlled, crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX, ATX, and placebo during a stop task, combined with fMRI within 19 medication-naive ADHD boys, and their potential normalization effects relative to 29 age-matched healthy boys. Compared with controls, ADHD boys under placebo showed bilateral ventrolateral prefrontal, middle temporal, and cerebellar underactivation. Within patients, MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation, which correlated with enhanced inhibitory capacity. Relative to controls, both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo, while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX. The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX.
authors.affiliation: Department of Child Psychiatry.
authors.forename: Ana
authors.initials: A
authors.lastname: Cubillo
authors.forename: Anna B
authors.initials: AB
authors.lastname: Smith
authors.forename: Nadia
authors.initials: N
authors.lastname: Barrett
authors.forename: Vincent
authors.initials: V
authors.lastname: Giampietro
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brammer
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Katya
authors.initials: K
authors.lastname: Rubia
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000704:Analysis of Variance; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D016022:Case-Control Studies; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D009068:Movement / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011437:Propylamines / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride