Question

• 10yo h/o ADHD poorly controlled on Ritalin, Adderall, and Concerta. Are there other alternatives?

Clinical Bottom Lines

1. Atomoxetine is a nonstimulant alternative equal in efficacy to Methylphenidate.

Summary of Key Evidence

1. This was a randomized, open-label study of Atomoxetine vs Methylphenidate over a 10-week study period.1
2. At study entry, mean ADHD RS Total T scores were 2.7 standard deviations above age and gender norms for both groups. At study endpoint, mean Total T scores approached age and gender norms for both Atomoxetine and Methylphenidate groups.1
3. There was no statistical difference between Atomoxetine and Methylphenidate for any prespecified outcome measure. They performed similarly across investigator, parent, and teacher ratings, as well as for different ADHD subtypes (Hyperactivity/ Impulsivity, Inattention).1

Additional Comments

• A blocked-randomization design was intended to give roughly four times as many patients in the Atomoxetine group which makes direct comparisons between the groups more difficult.1
• Only 50-60% of both groups completed the 10-week study period, but >90% of both groups had at least one postbaseline visit which was carried forward to permit inclusion in the final analysis.1
• Atomoxetine caused statistically significant increases in heart rate and blood pressure which were not clinically significant. This has been confirmed in other studies.1-4
• Atomoxetine was associated with slightly greater weight loss than Methylphenidate (0.6 kg vs 0.1 kg over 10 weeks). Other studies have suggested catch-up growth thereafter.1-4
• This particular study found statistically significant increases in vomiting and somnolence in the Atomoxetine group, and no statistically significant difference in the occurrence of insomnia. Most other studies have shown Atomoxetine to cause less insomnia than Methylphenidate, and not to be associated with other side effects other than weight loss as above.1-4
• Atomoxetine works via norepinephrine reuptake inhibition.
• Costs for one month supply (as per UM Outpatient Pharmacy):
  Ritalin $35.70
  Adderall $46.60
  Concerta $75.50
  Strattera $91.50

Citation

1. Kratochvil CJ, Heligenstein JH, Dittman R, et al: Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 2002;41:776-84.
2. Michelson D, Faries D, Wernicke J, et al: Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder; A randomized, placebo-controlled, dose-response study. Pediatrics 2001;108:e83.
   
3. Michelson D, Allen AJ, Busner J, et al: Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: A randomized, placebo-controlled study. Am J Psychiatry 2002;159:1896-901.
   
4. Biederman J, Heiligenstein JH, Faries DE: Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder. Pediatrics 2002;110:e75.
   

CAT Author: Satish Gopal, MD, MPH

CAT Appraisers: Jon Fliegel, MD

Date appraised: February 24, 2003