Atomoxetine Tolerability and Adverse Events in Autism Spectrum Disorders in the Multisite Charts Study

Friday, May 15, 2015: 11:30 AM-1:30 PM
Imperial Ballroom (Grand America Hotel)
J. A. Hellings1, S. L. Hyman2, B. L. Handen3, T. Smith4, P. Corbett-Dick5, R. Tumuluru6, L. E. Arnold7 and M. G. Aman8, (1)Psychiatry, The Ohio State University Nisonger Center McCampbell Hall, Columbus, OH, (2)Pediatrics, University of Rochester School of Medicine, Rochester, NY, (3)University of Pittsburgh School of Medicine, Pittsburgh, PA, (4)601 Elmwood Ave, Box 671, University of Rochester, Rochester, NY, (5)Neurodevelopmental and Behavioral Pediatrics, University of Rochester Medical Center, Rochester, NY, (6)Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, (7)Nisonger Center, The Ohio State University, Columbus, OH, (8)The Nisonger Center UCEDD, Ohio State University, Columbus, OH

Symptoms of attention deficit hyperactivity disorder (ADHD) occur in up to one third of children with autism spectrum disorders (ASD). Children with ASD are more prone to irritability, insomnia and gastrointestinal (GI) problems than TD children, and show a much lower response to, and tolerance of, stimulant treatment than TD children. Atomoxetine, a non-stimulant ADHD treatment, in typically developing (TD) children showed a response rate of 60%, and effect size 0.65 for ADHD (Correll & Schwartz, 2014), and has shown promise for ADHD symptoms in ASD in preliminary studies. 


The Children with Hyperactivity and Autism Research Treatment Study (CHARTS) includes a multisite, 10-week, randomized, double- blind, placebo-controlled, 2x2 trial of ATX versus placebo (PBO) in groups randomized to Parent Training (PT) or No PT, with a 24-week open ATX extension. PT comprised up to 9 weekly sessions of 1 to 1.5 hours of outpatient training. ATX was used at up to 1.8mg/kg/day. Response rates were higher in ATX than PBO in both PT and No PT groups (p= 0.015, Fisher exact test). We examine adverse events (AEs) and tolerability between the groups acutely (by 10 weeks), longer term (34 weeks), and for drop- outs.


AEs were ascertained using an ATX-specific side effect review scale (parent-rated) at each visit. Clinicians established whether AEs were new or ongoing, rated their severity and developed an action plan. Tolerability was monitored with physical examinations at each visit, as well as EKG and laboratory tests at baseline, Week 10, and Week 34. Using Fisher exact tests, we compared the frequency of AEs and dropouts across groups at Week 10. In our poster, we will also present group comparisons at Weeks 10 and 34 for (1) cardiovascular, growth, and laboratory results, (2) AEs relative to dose, and (3) concomitant medications.


Irritability was less frequent in the ATX+ PT group than in the ATX group (p= 0.04), and in PT than No PT (p=0.007). Appetite decrease (p=0.04), and possibly abdominal pain (p=0.07) were more common in ATX than PBO. No other statistically significant group differences in AEs were observed.

One SAE occurred in the ATX group in the first 10 weeks: a child with a known seizure disorder and low antiseizure drug concentration had a seizure and ED visit at week 8; this child continued in the study with antiseizure medication dosage adjustment, neurologist and clinician monitoring.

More subjects dropped out of PBO and PBO+PT than the ATX and ATX+PT groups. Fewer subjects dropped out in Drug versus No Drug (p=0.20); fewer dropped out in PT versus No PT (p=0.05).


ATX was well tolerated acutely in children with ASD, and was not related to more dropouts or SAEs. More comprehensive and longer-term data will also be presented.