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

Abstract

Objective: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial of atomoxetine (ATX) and parent training (PT).

Methods: In a 2 × 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [≤1.8 mg/kg/d], and then maintained until week 10. Responders continued to week 34 or nonresponse. Placebo nonresponders had a 10-week ATX open trial; ATX nonresponders were treated clinically. All continued to week 34. With no further treatment from the study, all were invited to follow-up (FU) at 1.5 years postbaseline; 94 (73%) participated. Changes from Week 34 to FU and from baseline to FU were tested by one-way analysis of variance or chi-squared test. PT versus no PT was tested by chi-squared test, Fisher's exact test, Welch's t-test, Student's t-test, and Mann-Whitney's U test.

Results: For the whole sample, the primary outcomes (parent-rated ADHD on the Swanson, Nolan, and Pelham [SNAP] scale and noncompliance on the Home Situations Questionnaire [HSQ]) deteriorated mildly from week 34 to FU, but were still substantially better than baseline (SNAP: t = 12.177, df = 93, p < 0.001; HSQ: t = 8.999, df = 93, p < 0.001). On the SNAP, 61% improved ≥30% from baseline (67% did at week 34); on noncompliance, 56% improved ≥30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication.

Conclusions: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).

Keywords: ADHD; atomoxetine; autism spectrum disorder; follow-up studies; parent training.

FIG. 1.

ADHD symptom scores (A) and noncompliance (B) over time by original treatment assignment, and by PT versus no PT (C, D), last observation carried forward to week 34. Although some of the week 34 end-of-treatment improvement is lost by week 78 FU, the endpoint remains significantly better than baseline for all originally assigned treatment groups. Those originally assigned placebo had an open atomoxetine trial after week 10 if needed. Difference in change from baseline to week 78 between placebo and 3 pooled active treatments: p = 0.044 for SNAP ADHD rating and p = 0.023 for HSQ noncompliance score. Change difference between PT and no PT is not significant. Vertical line at week 34 indicates end-of-study treatment. ADHD, attention-deficit/hyperactivity disorder.

FIG. 2.

Change in proportion of responders from week 34 to follow-up. Response is defined as >30% improvement in the relevant scale, Swanson, Nolan, and Pelham attention-deficit/hyperactivity disorder symptom ratings for attention responder and Home Situations Questionnaire for compliance responder.