There have been relatively few randomized clinical trials of pharmacology for attention-deficit/hyperactivity (ADHD) in children with Autism Spectrum Disorders (ASD). Studies involving stimulant medications have generally found poorer response rates and higher rates of intolerable side effects than in typically developing children with ADHD. Atomoxetine (Strattera) was approved by the FDA in January 2003 for treatment of ADHD. A nonstimulant, it inhibits the presynaptic norephinephrine transporter. There have been only four studies (three open and one small double-blind) examining this medication in children with ASD. Behavioral treatments, such as training parents in the use of behavioral interventions (PMT), are also standard treatments for ADHD in typically developing children. While PMT also has long been used in ASD, it has rarely been studied in combination with psychopharmacologic treatment in this population. This proposal addresses four objectives: a) to conduct a double-blind, placebo-controlled, 10-week parallel-group comparison of atomoxetine (ATX) versus placebo on i) clinician- and parent-rated behavior, ii) direct observations of behavior, iii) cognitive/performance measures of attention, and iv) adverse events in 156 children with ASD (78 treated with ATX, 78 with placebo);b) to conduct a 10-week parallel-group comparison of PMT versus no-PMT on behavioral measures of compliance in 156 children with ASD (78 with PMT, 78 without PMT) c) to conduct a 10-week parallel-group comparison of combined (ATX plus PMT) vs. single treatment (PMT alone) on measures of compliance in 156 children with ASD;and d) to compare the long-term maintenance of efficacy, safety, and tolerability of ATX and PMT via an open-label 6-month extension trial of responders. Medication doses will be titrated against benefit and side effects over the first 6 weeks (ATX to a cap of 1.8 mg/kg/day). PMT will be 10 sessions, 1-1.5 hr. each, modeled on the RUPP Autism Network PMT. Data analyses will capitalize on the power of a 2 x 2 analysis where appropriate. Children with ASD have been neglected in pharmacological research, placing an enormous burden on health care and educational systems. This trial has the potential to provide answers regarding optimal treatment (both psychosocial and pharmacological) for a sizeable subgroup of children with ASD who experience symptoms of over activity and inattention.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Interventions Committee for Disorders Involving Children and Their Families (ITVC)
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Sarampote, Christopher S
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University of Rochester
Schools of Dentistry
United States
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Barrie, Elizabeth S; Pinsonneault, Julia K; Sadee, Wolfgang et al. (2018) Testing genetic modifiers of behavior and response to atomoxetine in autism spectrum disorder with ADHD. J Dev Phys Disabil 30:355-371
Lecavalier, Luc; Pan, Xueliang; Smith, Tristram et al. (2018) Parent Stress in a Randomized Clinical Trial of Atomoxetine and Parent Training for Children with Autism Spectrum Disorder. J Autism Dev Disord 48:980-987
Hollway, Jill A; Aman, Michael G; Mendoza-Burcham, Marissa I et al. (2016) Caregiver Satisfaction with a Multisite Trial of Atomoxetine and Parent Training for Attention-Deficit/Hyperactivity Disorder and Behavioral Noncompliance in Children with Autism Spectrum Disorder. J Child Adolesc Psychopharmacol 26:807-814
Smith, Tristram; Aman, Michael G; Arnold, L Eugene et al. (2016) Atomoxetine and Parent Training for Children With Autism and Attention-Deficit/Hyperactivity Disorder: A 24-Week Extension Study. J Am Acad Child Adolesc Psychiatry 55:868-876.e2
Handen, Benjamin L; Aman, Michael G; Arnold, L Eugene et al. (2015) Atomoxetine, Parent Training, and Their Combination in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry 54:905-15
Aman, Michael G; Smith, Tristram; Arnold, L Eugene et al. (2014) A review of atomoxetine effects in young people with developmental disabilities. Res Dev Disabil 35:1412-24