Atomoxetine, Placebo, and Parent Training in Autism

Background:  Children with ASD often have co-occurring behavior problems such as inattention, hyperactivity, irritability, anxiety and noncompliance. However, available research provides little guidance on whether to select a behavioral intervention, medication, or both for treatment of an individual child with ASD.  

Objectives:  This three-center randomized clinical trial evaluated relative efficacy of psychosocial treatment (parent training; PT) and atomoxetine (ATX) for treating ADHD symptoms and noncompliance in children with ASD. 

Methods: We enrolled 128 children (age 5-14 years) with ASD and ADHD symptoms in a 10-week, double-blind trial with a 24-week extension (M age = 8.14 years, SD = 2.08; 108 males). Subjects were randomized in equal numbers to: a) ATX+PT, b) ATX alone, c) placebo+PT and d) placebo alone, balanced by site and mental age (<6.0 vs. >6.0 years). Atomoxetine was optimized over the first six weeks (to a maximum of 1.8 mg/kg) and PT occurred weekly, involving nine core sessions and a home visit. During the Extension, responders continued double-blind; non-responders had the blind broken and received an open trial of atomoxetine or an alternative medication. Primary outcome measures were the parent-rated SNAP-IV and Home Situations Questionnaire (HSQ), and the Clinical Global Impressions Scale (CGI), completed by an independent evaluator blind to group assignment. Responders were identified based on parent ratings (SNAP-IV for ADHD and HSQ for noncompliance) and ADHD CGI-Improvement rating of “much” or “very much” improved. We compared response rates using Fisher Exact Tests.

Results: By preliminary analyses, at Week 10, the highest ADHD response rates, occurred in the groups that received ATX (ATX alone = 47%, ATX+PT = 44%), followed by PT+Placebo (28%) and Placebo Alone (19%). Noncompliance response rates were highest in the groups that received either ATX or PT Alone (ATX Alone = 44% and PT+Placebo = 38%), compared to ATX+PT = 22% and Placebo Alone = 16%).

At Week 34, both ADHD and noncompliance response rates, based upon original group assignment even though double-blind nonresponders at that point were receiving different pharmacotherapy, were higher in all three groups originally assigned active treatment than in the group originally assigned Placebo Alone. ADHD response rates were ATX Alone = 63%, PT+Placebo = 59%, ATX+PMT = 56%, Placebo Alone = 31%. Noncompliance response rates were ATX Alone = 59%, PT+Placebo = 56%, ATX+PMT = 53%, Placebo Alone = 34%.

Conclusions:  

Both ATX and PT appeared effective in treating ADHD and noncompliance in this sample of children with ASD. However, the combination of the two treatments did not result in greater gains on primary outcome measures. In addition, ATX may have led to a more rapid improvement in ADHD symptoms than did PT. Analyses of secondary measures may yield additional information about the relative efficacy of ATX, PT, and ATX+PT compared to placebo and help explain the somewhat idiosyncratic impact of PT within the combined treatment. Based upon our preliminary analysis, both ATX and PT appear to be reasonable options for treating symptoms of overactivity, inattention, and noncompliance in children with ASD.