Atomoxetine, Parent Training, and Their Combination in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.
OBJECTIVE
Impairments associated with attention-deficit/hyperactivity disorder (ADHD) and noncompliance are prevalent in children with autism spectrum disorder (ASD). However, ADHD response to stimulants is well below rates in typically developing children, with frequent side effects. Group studies of treatments for noncompliance are rare in ASD. We examined individual and combined-effectiveness of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance.


METHODS
In a 3-site, 10-week, double-blind, 2 × 2 trial of ATX and PT, 128 children (ages 5-14 years) with ASD and ADHD symptoms were randomized to ATX, ATX+PT, placebo+PT, or placebo. ATX was adjusted to optimal dose (capped at 1.8 mg/kg/day) over 6 weeks and maintained for 4 additional weeks. Nine PT sessions were provided. Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson, Nolan and Pelham (SNAP) scale and Home Situations Questionnaire (HSQ).


RESULTS
On the SNAP, ATX, ATX+PT and placebo+PT were each superior to placebo (effect sizes 0.57-0.98; p values of .0005, .0004, and .025, respectively). For noncompliance, ATX and ATX+PT were superior to placebo (effect sizes 0.47-0.64; p values .03 and .0028, respectively). ATX was associated with decreased appetite but was otherwise well tolerated.


CONCLUSIONS
Both ATX and PT resulted in significant improvement on ADHD symptoms, whereas ATX (both alone and combined with PT) was associated with significant decreases on measures of noncompliance. ATX appears to have a better side effects profile than psychostimulants in the population with ASD.


BACKGROUND
Atomoxetine, Placebo and Parent Management Training in Autism; http://clinicaltrials.gov/; NCT00844753.
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh. Electronic address: handenbl@upmc.edu.
Benjamin L
BL
Handen
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
Michael G
MG
Aman
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
L Eugene
LE
Arnold
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Susan L
SL
Hyman
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh.
Rameshwari V
RV
Tumuluru
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
Luc
L
Lecavalier
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Patricia
P
Corbett-Dick
Center for Biostatistics, Ohio State University.
Xueliang
X
Pan
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
Jill A
JA
Hollway
Center for Biostatistics, Ohio State University.
Kristin A
KA
Buchan-Page
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Laura B
LB
Silverman
Center for Biostatistics, Ohio State University.
Nicole V
NV
Brown
Center for Biostatistics, Ohio State University.
Robert R
RR
Rice
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
Jessica
J
Hellings
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Daniel W
DW
Mruzek
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh.
Sarah
S
McAuliffe-Bellin
The Nisonger Center UCEDD, Ohio State University, Columbus, OH.
Elizabeth A
EA
Hurt
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Melissa M
MM
Ryan
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Lynne
L
Levato
Division of Neurodevelopmental and Behavioral Pediatrics at the University of Rochester, Rochester, NY.
Tristram
T
Smith
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000069445:Atomoxetine Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D000067290:Behavior Rating Scale; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010290:Parents / Q000193:education*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States
D018759:Adrenergic Uptake Inhibitors; D000069445:Atomoxetine Hydrochloride
ADHD; atomoxetine; autism spectrum disorder; clinical trial; parent training