Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial.
OBJECTIVE
To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD).


METHODS
Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6 weeks each, separated by 1-week washout. Slopes for each condition were compared by paired t test.


RESULTS
In 2004-2005, 12 boys and 4 girls (7 with autistic disorder, 1 Asperger's, 8 pervasive developmental disorder not otherwise specified) all completed at least 3 weeks of each condition. On the primary outcome, the Hyperactivity subscale of the Aberrant Behavior Checklist, ATX was superior to placebo (p =.043, effect size d = 0.90). It was also superior on a 0 to 3 rating of nine DSM-IV ADHD hyperactive/impulsive symptoms (p =.005, d = 1.27), but missed significance on nine inattentive symptoms (p =.053, d= 0.89). Nine subjects responded to ATX, four to placebo (25% improvement on the Hyperactivity subscale plus Clinical Global Impressions-Improvement of 1-2. One was rehospitalized for recurrent violence on ATX. Adverse events were otherwise tolerable, with no tendency to stereotypy.


CONCLUSIONS
ATX appears safe and effective for treating hyperactivity in some children with autism spectrum disorders. The effect appears as large as in a multisite methylphenidate trial in the same population, with fewer intolerable side effects. Further study in autism spectrum disorders is indicated.
Arnold
L Eugene
LE
The authors are with Ohio State University's Nisonger Center, Columbus. Electronic address: arnold.6@osu.edu.
Aman
Michael G
MG
The authors are with Ohio State University's Nisonger Center, Columbus.
Cook
Amelia M
AM
The authors are with Ohio State University's Nisonger Center, Columbus.
Witwer
Andrea N
AN
The authors are with Ohio State University's Nisonger Center, Columbus.
Hall
Kristy L
KL
The authors are with Ohio State University's Nisonger Center, Columbus.
Thompson
Susan
S
The authors are with Ohio State University's Nisonger Center, Columbus.
Ramadan
Yaser
Y
The authors are with Ohio State University's Nisonger Center, Columbus.
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000453:epidemiology*; D001321:Autistic Disorder / Q000453:epidemiology*; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011437:Propylamines / Q000627:therapeutic use*
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride