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Atomoxetine vs. Methylphenidate for ADHD

Both are more effective than placebo, but the stimulant remains the first-line choice.

Atomoxetine is the only norepinephrine reuptake inhibitor currently approved in the U.S. for treating ADHD. In a rigorously designed, two-part study, researchers compared atomoxetine with the standard drug methylphenidate (MPH).

First, 516 children aged 6 to 16 years with any ADHD subtype were randomly assigned in a 3:3:1 ratio to atomoxetine, osmotically released MPH, or placebo for 6 weeks. Maximum dose was 54 mg for MPH and 1.8 mg/kg for atomoxetine. Both atomoxetine and MPH were significantly more efficacious than placebo (response rates, 45%, 56%, and 24%, respectively), and MPH was statistically superior to atomoxetine.

Then, MPH recipients were switched in double-blind fashion to atomoxetine for 6 weeks (the original atomoxetine recipients entered a dose-adjustment trial; results not reported). Among the 178 patients switched to atomoxetine, 34% responded to either MPH or atomoxetine, but not both; 44% responded to both; and 22% responded to neither. Of the atomoxetine nonresponders, 42% had previously responded to MPH, and of the MPH nonresponders, 43% responded to atomoxetine.

Comment: After this study was begun, the U.S. Food and Drug Administration increased the maximum dose of osmotically released MPH to 72 mg/day and decreased the maximum atomoxetine dose to 1.4 mg/kg/day, but these changes are unlikely to have affected the outcome. The findings support MPH as a first-line medication due to its superior efficacy. In addition, because MPH products have been used for many decades, their long-term effects on growth and development are better known. If MPH is not effective for a patient, these findings strongly support trying an alternative medication. But before trying atomoxetine, clinicians should first turn to dexamphetamine products, which, like MPH, have been on the market for decades.

— Barbara Geller, MD

Published in Journal Watch Psychiatry April 14, 2008

Citation(s):

Newcorn JH et al. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: Acute comparison and differential response. Am J Psychiatry 2008 Feb 15; [e-pub ahead of print]. (http://dx.doi.org/10.1176/appi.ajp.2007.05091676)