Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder.
BACKGROUND
Atomoxetine is a nonstimulant drug being studied for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Results of 2 proof-of-concept studies are reported that tested the hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would be effective for the treatment of ADHD in school-aged children.


METHODS
Two identical 12-week, stratified, randomized, double-blind, placebo-controlled trials were conducted in children who met DSM-IV criteria for ADHD. The primary efficacy outcome measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score. Secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S).


RESULTS
A total of 291 patients were randomized in the 2 trials combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were randomized to atomoxetine, placebo, or methylphenidate. Patients with prior stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine significantly reduced ADHD RS total scores compared with placebo in each study (p <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study 2: p =.001) and CPRS-ADHD Index (Study 1: p =.023; Study 2: p <.001) also showed atomoxetine to be statistically significantly superior to placebo in reducing ADHD symptoms. Atomoxetine was found to be well tolerated in this population of pediatric patients.


CONCLUSIONS
Two studies of atomoxetine early in its development confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic uptake, was effective for the treatment of children with ADHD. In addition, atomoxetine was found to be well tolerated.
Spencer
Thomas
T
Massachusetts General Hospital, Boston, USA.
Heiligenstein
John H
JH
Biederman
Joseph
J
Faries
Douglas E
DE
Kratochvil
Christopher J
CJ
Conners
C Keith
CK
Potter
William Z
WZ
D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride