A 1.5-Year Follow-Up of Parent Training and Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms and Noncompliant/Disruptive Behavior in Autism

By Arnold, L. Eugene; Ober, Nicole et al. | Journal of Child and Adolescent Psychopharmacology, June 2018 | Go to article overview

A 1.5-Year Follow-Up of Parent Training and Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms and Noncompliant/Disruptive Behavior in Autism


Arnold, L. Eugene, Ober, Nicole, Aman, Michael G., Handen, Benjamin, Smith, Tristram, Pan, Xueliang, Hyman, Susan L., Hollway, Jill, Lecavalier, Luc, Page, Kristin, Rice Jr, Robert, Journal of Child and Adolescent Psychopharmacology


Address correspondence to: L. Eugene Arnold, MD, MEd, Nisonger Center UCEDD, The Ohio State University, 395E McCampbell Hall, 1581 Dodd Drive, Columbus, OH 43210, E-mail: l.arnold@osumc.edu

Introduction

Hyperactivity and other symptoms of attention-deficit/hyperactivity disorder (ADHD) are common in autism spectrum disorder (ASD) (Lecavalier 2006; Simonoff et al. 2008). Unlike its predecessor, the Diagnostic and Statistical Manual, 5th Edition (American Psychiatric Association 2013) allows both diagnoses concomitantly in children who meet criteria for both disorders, sanctioning what had become widespread clinical practice. Because ADHD symptoms are so frequent in ASD, it is important to understand whether the evidence-based interventions used for ADHD without ASD are appropriate for children who have both disorders. It is also important to examine what happens over time once those treatments have been started, an area with scant literature.

The Child Hyperactivity and Autism Research Treatment Study (CHARTS) randomly assigned 128 children with ASD who also met categorical and dimensional criteria for ADHD to atomoxetine (ATX) alone, ATX+parent training (PT) in behavioral management, placebo+PT, or placebo alone. The 10-week double-blind initial phase (Handen et al. 2015; Tumuluru et al. 2017) was followed by an extension to week 34 (Smith et al. 2016). We expected that PT effects would take more time to emerge, but would be longer lasting than ATX effects because PT teaches skills for parents to continue managing their child's behavior (Handen et al. 2015).

The double-blind initial phase showed that ATX, ATX+PT, and placebo+PT each resulted in more improvement than placebo alone on parent-rated ADHD symptoms (effect sizes d = 0.57-0.98, with p = 0.0005, 0.0004, and 0.025, respectively). The extension to week 34 showed that 59% of 10-week responders to the initial treatment continued to show response 6 months later and 37% of placebo nonresponders responded to an open ATX trial. Thus, the children in the study were generally better at the end (after 34 weeks) than when starting. The question then arises about how well that improvement holds up over even more time.

This article reports outcomes 1.5 years after baseline (week 78), about 10 months after cessation of study-provided 34-week treatment. During the follow-up (FU) interval from weeks 34 to 78, no systematic treatment was provided by the study; all participants returned to the clinic or other community care from which they had been recruited. Hypotheses were that (1) most of the 34-week improvement from baseline would be sustained at FU; (2) the majority would continue their 34-week response status to FU, whether responder or nonresponder; and (3) those whose parents received PT might fare better than those without PT.

Methods

We previously described the background of this study (Silverman et al. 2014). It was approved by the institutional review boards at all sites; parents/legal guardians signed informed permission and children assented if able.

Sample characteristics

Participants were 5.0-14.11 years old with a minimum mental age (MA) of 24 months, based on either the Stanford-Binet 5th Edition (Roid 2003) or Mullen Scales of Early Learning (Mullen 1989). All met criteria for an ASD (Autistic Disorder, Asperger's Disorder, Pervasive Developmental Disorder Not Otherwise Specified), by the Autism Diagnostic Interview-Revised (Rutter et al. 2003), and expert clinical evaluation using a DSM-IV-TR Interview (American Psychiatric Association 2000). They exhibited marked symptoms of overactivity and/or inattention at both home and school, based upon a mean item score ≥1.50 on the parent- and teacher-completed Swanson, Nolan, and Pelham (SNAP) scales (Bussing et al. 2008) and a Clinical Global Impression (CGI)-Severity score ≥4 (Guy 1976).

Participants were free of psychotropic medications (with the exception of stable doses of melatonin for sleep) for 2 weeks before randomization. …

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