title: Does atomoxetine improve executive function, inhibitory control, and hyperactivity? Results from a placebo-controlled trial using quantitative measurement technology.
abstract: The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD)-related symptoms assessed as standard variables of a computer-based continuous performance test (cb-CPT) combined with a motion-tracking (MT) device. This was a 2-arm, 8-week, randomized, double-blind, placebo-controlled study in patients with ADHD (6-12 years). Therapy with ATX started with 0.5 mg/kg per day for 1 week, followed by 7 weeks on the target dosage of 1.2 mg/kg per day. Primary outcomes were cb-CPT/MT standard scores after 8 weeks using mixed models for repeated measurements. In addition, investigator-rated ADHD Rating Scale (ADHD-RS), Weekly Ratings of Evening and Morning Behavior (WREMB), and Clinical Global Impression - Severity-ADHD (CGI-S-ADHD) scores were assessed. Of 128 patients randomized, 125 were evaluated (ATX/placebo: 63/62). Baseline characteristics were comparable in both groups (overall, 80.2% boys; mean [SD] age, 9.0 [1.79] years; comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis, 40.0% oppositional defiant disorder/conduct disorder; prior stimulant treatment, 24.8%; ADHD-RS total score, 36.99 [11.56]). At week 8, all cb-CPT/MT q-scores were significantly reduced versus placebo (all P < 0.001) with effect sizes (ESs) of reaction time (RT) variation (ES = 0.71), mean RT (ES = 0.41), number of microevents (ES = 1.00), commission error rate (ES = 0.50), distance of movement (ES = 0.90), area of movement (ES = 1.08), omission error rate (ES = 0.70), time active (ES = 0.69), motion simplicity (ES = 0.38), and normalized variance of RT (ES = 0.50). Secondary end points also improved significantly in favor of ATX: ADHD-RS (total score ES = 1.30, P < 0.001; hyperactivity/impulsivity subscore ES = 1.37, P < 0.001; inattention subscore ES = 1.07, P < 0.001), WREMB (total score ES = 1.00, P < 0.001; morning subscore ES = 0.59, P = 0.002; evening subscore ES = 1.02, P < 0.001), CGI-S-ADHD (ES = 1.11, P < 0.001). The results of this study show that ATX for 8 weeks significantly reduced ADHD-related symptoms as measured by the cb-CPT/MT.
authors.affiliation: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, Germany. Peter.Wehmeier@vitos-weilmuenster.de
authors.forename: Peter M
authors.initials: PM
authors.lastname: Wehmeier
authors.forename: Alexander
authors.initials: A
authors.lastname: Schacht
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ulberstad
authors.forename: Martin
authors.initials: M
authors.lastname: Lehmann
authors.forename: Christian
authors.initials: C
authors.lastname: Schneider-Fresenius
authors.forename: Gerd
authors.initials: G
authors.lastname: Lehmkuhl
authors.forename: Ralf W
authors.initials: RW
authors.lastname: Dittmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D003936:Diagnosis, Computer-Assisted; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000187:drug effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride