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Osmotically released methylphenidate is superior to atomoxetine in the treatment of ADHD


  • In children & adolescents with ADHD, is treatment with stimulant medication more effective than treatment with atomoxetine for improvement in symptoms?

Clinical Bottom Lines

  1. Children and adolescents with ADHD had clinical improvement with both atomoxetine and osmotically released methylphenidate; the NNT for atomoxetine was 5 and was 3 for methylphenidate.
  2. A greater number of children had clinical improvement when treated with methylphenidate than atomoxetine with a NNT of 9 , however this difference was found to be statistically significant in only those with previous stimulant exposure.
  3. It is difficult to determine if the differences in change in score for secondary measures are clinically significant, although they were found to be statistically significant.
  4. More information on efficacy and adverse events are needed before one medication is clearly a better choice.

Summary of Key Evidence

  1. Children ages 6-16 years meeting DSM-IV criteria for ADHD were randomized to receive atomoxetine, methylphenidate or placebo for 6week treatment course. Clinician and patient were blinded to group randomization. Each randomization group had similar prognosis prior to and throughout the study. Exclusion criteria included having a seizure, bipolar, psychotic, tic or anxiety disorder and children with previous stimulant exposure who were nonresponders or had intolerable adverse events.1
  2. Atomoxetine was administered as a divided twice-daily dose of 0.8-1.8mg/kg/day. Following study completion the maximum dose of atomoxetine was determined to be 1.4mg/kg/day. Osmotically released methyphenidate was administered as a single morning dose of 15-54mg/day. Following the study completion, osmotically released methylphenidate was aproved for use in doses up to 72mg/day in adolescents. 1
  3. The primary response measure was investigator administered and scored ADHD rating scale. Response was defined as decrease from baseline of 40% or more in total ADHD Rating scale at week 6. 1
  4. Children treated with methylphenidate had statistically significant greater decreases in scores for many primary and secondary outcomes, in comparison with those treated with atomoxetine. 1 5. 45% of patients responded to atomoxetine, 56% responded to osmotically released methylphenidate and 24% responded to placebo. There was a statistically significant difference in response rate between all of these variables. 1

Additional Comments

  • Adverse effects appear to be similar for both medications. 1
  • Kratochvil et al. found increase in blood pressure and heart rate with both atomoxetine and methylphenidate. 3
  • AAP Clinical Practice Guidelines recommend the use of stimulants as first line treatment, however atomoxetine was not established as a treatment at that time.2


  1. Newcorn J. et al. Atomoxetine and Osmotically Released Methylphenidate for the Treatment of Attention Deficit Hyperactivity Disorder: Acute Comparison and Differential Response. Am J Psychiatry 2008; 165:721-730
  2. American Academy of Pediatrics, Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Treatment of the child with attention-eficit/hyperactivity disorder. Pediatrics. 2001;108:1033–1044
  3. Kratochvil C. et al. Atomoxetine and methylphenidate Treatment in Children with ADHD: A Prospective, Randomized, Open-Label Trial. J Am Acad Child Adolesc Psychiatry. 2002; 41:776-784

CAT Author: Elizabeth Hastings, MD

CAT Appraisers: Robert Schumacher, MD

Date appraised: January 21, 2009

Last updated June 15, 2009
Department of Pediatrics and Communicable Diseases
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