How oppositionality, inattention, and hyperactivity affect response to atomoxetine versus methylphenidate: a pooled meta-analysis

J Atten Disord. 2012 May;16(4):314-24. doi: 10.1177/1087054710389989. Epub 2011 Feb 2.


Objective: To assess how threshold oppositional defiant disorder (ODD), inattention, and hyperactivity-impulsivity affect the response to atomoxetine versus methylphenidate.

Method: Systematic review of randomized controlled trials (RCTs; ≥6 weeks follow-up). The primary measure was core symptom response-≥40% reduction in ADHD Rating Scale-IV-Parent Version: investigator administered and scored total or domain subscores, as appropriate.

Results: Data from 1,391 children and adolescents (823 atomoxetine, 568 methylphenidate; 7 RCTs) were meta-analyzed. The mean difference in response rates for patients with ODD was 0.6% (95% confidence interval [CI] = -11.9%-13.1%). The "without ODD" patient group showed significant between-trial heterogeneity (p < .001). Response rate differences for patients meeting the threshold for inattention or hyperactivity-impulsivity were -3.1% (95% CI = -11.5%-5.3%) and -4.9% (95% CI = -14.3%-4.4%), respectively.

Conclusions: Meeting the threshold criteria for oppositionality, inattention, or hyperactivity-impulsivity did not alter core ADHD symptom response to atomoxetine versus methylphenidate, which was equivalent.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit and Disruptive Behavior Disorders / drug therapy*
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Humans
  • Hyperkinesis / drug therapy*
  • Methylphenidate / therapeutic use*
  • Propylamines / therapeutic use*
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Propylamines
  • Methylphenidate
  • Atomoxetine Hydrochloride