Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response

Am J Psychiatry. 2008 Jun;165(6):721-30. doi: 10.1176/appi.ajp.2007.05091676. Epub 2008 Feb 15.


Objective: Response to atomoxetine, a nonstimulant norepinephrine-specific reuptake inhibitor, was compared with the effect of osmotic-release oral methylphenidate, a long-acting methylphenidate preparation, in patients with attention deficit hyperactivity disorder (ADHD).

Method: In a large placebo-controlled, double-blind study, patients ages 6-16 with ADHD, any subtype, were randomly assigned to receive 0.8-1.8 mg/kg per day of atomoxetine (N=222), 18-54 mg/day of osmotically released methylphenidate (N=220), or placebo (N=74) for 6 weeks. The a priori specified primary analysis compared response (at least 40% decrease in ADHD Rating Scale total score) to osmotically released methylphenidate with response to atomoxetine and placebo. After 6 weeks, patients treated with methylphenidate were switched to atomoxetine under double-blind conditions.

Results: The response rates for both atomoxetine (45%) and methylphenidate (56%) were markedly superior to that for placebo (24%), but the response to osmotically released methylphenidate was superior to that for atomoxetine. Each medication was well tolerated, with completion rates and discontinuations for adverse events not significantly different from those for placebo. Of the 70 subjects who did not respond to methylphenidate, 30 (43%) subsequently responded to atomoxetine. Likewise, 29 (42%) of the 69 patients who did not respond to atomoxetine had previously responded to osmotically released methylphenidate.

Conclusion: Response was significantly greater with osmotically released methylphenidate than with atomoxetine. One-third of patients who received methylphenidate followed by atomoxetine responded better to one or the other, suggesting that there may be preferential responders.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / administration & dosage*
  • Adrenergic Uptake Inhibitors / adverse effects
  • Atomoxetine Hydrochloride
  • Central Nervous System Stimulants / administration & dosage*
  • Central Nervous System Stimulants / adverse effects
  • Child
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Methylphenidate / adverse effects
  • Personality Assessment
  • Propylamines / administration & dosage*
  • Propylamines / adverse effects
  • Treatment Outcome


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Propylamines
  • Methylphenidate
  • Atomoxetine Hydrochloride