Atomoxetine versus stimulants for treatment of attention deficit/hyperactivity disorder

Ann Pharmacother. 2006 Jun;40(6):1134-42. doi: 10.1345/aph.1G582. Epub 2006 May 30.


Objective: To identify, review, and analyze studies comparing atomoxetine with psychostimulants with the intent of determining the role of atomoxetine in the pharmacologic management of attention deficit/hyperactivity disorder (ADHD).

Data sources: Primary, review, and meta-analysis articles were identified by a MEDLINE search (1966-December 2005). MeSH headings used in the search include: attention deficit/hyperactivity disorder, ADHD, atomoxetine, stimulants, psychostimulants, methylphenidate, and amphetamine salts. Relevant data presented at professional meetings that we attended were also identified.

Study selection and extraction: All clinical studies comparing atomoxetine with psychostimulants, regardless of study design, were evaluated. Relevant efficacy and safety data from these studies were included in the discussion.

Data synthesis: At time of writing, 5 head-to-head trials had compared psychostimulants and atomoxetine in the treatment of ADHD. No significant difference between atomoxetine and methylphenidate immediate-release were found on the ADHD Rating Scale total score. Osmotic oral release system (OROS) methylphenidate showed significantly greater improvement at weeks 1 and 2, and significantly more patients treated with OROS methylphenidate were classified as responders. Patients on both atomoxetine and mixed amphetamine salts extended-release (MAS XR) showed significant improvements at endpoint over baseline; however, Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores were significantly better with MAS XR. Tolerability was similar between atomoxetine and stimulant medications.

Conclusions: Based on available evidence, psychostimulants are regarded as first-line pharmacologic treatment for children and adolescents with ADHD, as the efficacy and safety of these agents have been well established based on clinical trials and extensive naturalistic use. Adverse effects in some patients and abuse potential have led to the search for new treatments. Atomoxetine represents an alternative treatment for ADHD and is unlikely to be associated with abuse; however, long-term safety data are needed to further establish its place in therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / therapeutic use*
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Clinical Trials as Topic
  • Humans
  • Propylamines / adverse effects
  • Propylamines / therapeutic use*
  • Substance-Related Disorders


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Propylamines
  • Atomoxetine Hydrochloride