Atomoxetine effects on executive function as measured by the BRIEF--a in young adults with ADHD: a randomized, double-blind, placebo-controlled study.

Lenard A Adler,Todd M Durell,David B Clemow,David W Williams,Mark Bellgrove

doi:10.1371/journal.pone.0104175

Abstract

ObjectiveTo evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD).MethodsIn this Phase 4, multi-center, double-blind, placebo-controlled trial, young adults (18–30 years) with ADHD were randomized to receive atomoxetine (20–50 mg BID, N = 220) or placebo (N = 225) for 12 weeks. The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) consists of 75 self-report items within 9 nonoverlapping clinical scales measuring various aspects of executive functioning. Mean changes from baseline to 12-week endpoint on the BRIEF-A were analyzed using an ANCOVA model (terms: baseline score, treatment, and investigator).ResultsAt baseline, there were no significant treatment group differences in the percentage of patients with BRIEF-A composite or index T-scores ≥60 (p>.5), with over 92% of patients having composite scores ≥60 (≥60 deemed clinically meaningful for these analyses). At endpoint, statistically significantly greater mean reductions were seen in the atomoxetine versus placebo group for the BRIEF-A Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognitive Index (MI) scores, as well as the Inhibit, Self-Monitor, Working Memory, Plan/Organize and Task Monitor subscale scores (p<.05), with decreases in scores signifying improvements in executive functioning. Changes in the BRIEF-A Initiate (p = .051), Organization of Materials (p = .051), Shift (p = .090), and Emotional Control (p = .219) subscale scores were not statistically significant. In addition, the validity scales: Inconsistency (p = .644), Infrequency (p = .097), and Negativity (p = .456) were not statistically significant, showing scale validity.ConclusionStatistically significantly greater improvement in executive function was observed in young adults with ADHD in the atomoxetine versus placebo group as measured by changes in the BRIEF-A scales.Trial RegistrationClinicalTrials.gov NCT00510276

Highlights

A growing body of evidence suggests that attention-deficit/ hyperactivity disorder (ADHD) consists of more than just its primary diagnostic symptoms of inattention, impulsiveness, and hyperactivity
Deficits in any one aspect of executive functioning might contribute to impairment, some of which could be associated with ADHD [3]
There was a statistically significantly greater decrease in mean change (6 standard deviation) from baseline to last observation demonstrated in the atomoxetine group compared with the placebo group for the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) overall Global Executive Composite (GEC) score and the Behavioral Regulation Index (BRI) and Metacognitive Index (MI) scores (Table 3)

Summary

Introduction

A growing body of evidence suggests that attention-deficit/ hyperactivity disorder (ADHD) consists of more than just its primary diagnostic symptoms of inattention, impulsiveness, and hyperactivity. Some researchers argue that symptoms of deficient executive functioning (EF) are involved in ADHD symptomology and consider ADHD a disorder of executive functioning dysregulation [1], [2]. There are 2 ADHD dimensions believed to be important to executive functioning: the inattentive dimension (working memory, planning/problem-solving) and the hyperactive, impulsive dimension (behavioral inhibition, motor regulation) [3], [4]. Multiple studies have shown that children with ADHD are more likely to have executive function impairments that persist into adulthood [4], with neuropsychological studies consistently finding adults with ADHD to have impairments on measures of executive function [6]. Deficits in any one aspect of executive functioning might contribute to impairment, some of which could be associated with ADHD [3]

Methods

Results

Conclusion