title: A meta-analysis of the consistency of atomoxetine treatment effects in pediatric patients with attention-deficit/hyperactivity disorder from 15 clinical trials across four geographic regions.
abstract: OBJECTIVE
  Atomoxetine has been approved as a treatment for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in the United States, throughout Europe, and in other countries. This meta-analysis was to assess the consistency of the treatment effect of atomoxetine across four global geographic regions.
  
  
  METHODS
  Data from 15 acute, double-blind, placebo-controlled trials were pooled (2 in Asia, 4 in Europe, 8 in North America, and 1 in Russia), yielding 2569 pediatric patients with ADHD. Improvements during 6-10 weeks of atomoxetine treatment were evaluated using the ADHD Rating Scale-IV or the Swanson, Nolan, and Pelham Scale-Revised. Consistency across regions was assessed by an interaction test and Higgins I(2). Consistency of one region versus other regions was assessed by effect sizes of individual regions and pairwise differences.
  
  
  RESULTS
  Patient demographics were generally similar across regions. More patients from Asia met diagnostic criteria for ADHD inattentive subtype and fewer for combined subtype compared with patients from Europe, North America, or Russia. Asian patients had a lower mean baseline ADHD total score and mean hyperactivity/impulsivity subscore. Treatment effects showed marginal inconsistency and moderate heterogeneity among the regions (percentage of patients achieving a 40% decrease from baseline ADHD scores, atomoxetine versus placebo: Asia 39.6%, 24.0%; Europe 40.2%, 12.1%; North America 45.3%, 21.7%; Russia 54.2%, 33.3%). Inconsistency was observed primarily in Asia versus the other regions. Completion rates with atomoxetine were higher in Asia and Russia (94.4% and 94.3%, respectively) than in Europe (84.3%) or North America (80.4%).
  
  
  CONCLUSIONS
  Atomoxetine was demonstrated as an effective treatment for ADHD in 15 clinical trials from four global regions. The current meta-analysis has revealed a degree of heterogeneity in treatment efficacy across regions, most notably in the comparison of Asian patients relative to those from the other regions.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. tanaka_yoko_x1@lilly.com
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Luis A
authors.initials: LA
authors.lastname: Rohde
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.forename: Peter D
authors.initials: PD
authors.lastname: Feldman
authors.forename: Himanshu P
authors.initials: HP
authors.lastname: Upadhyaya
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005843:Geography; D006801:Humans; D008297:Male; D011437:Propylamines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride