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

Abstract

Objective: To evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: In 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).

Results: At 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.

Conclusion: Statistically 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 registration: ClinicalTrials.gov NCT00510276.

Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: Dr. Adler has received research funding from Bristol-Myers Squibb, Chelsea Therapeutics, Eli Lilly and Company and/or one of its subsidiaries, National Institute of Drug Abuse, Pfizer, Shire; served on advisory boards or as a consultant for Astra Zeneca Pharmaceuticals, Eli Lilly and Company and/or one of its subsidiaries, i3 Research, Major League Baseball, Mindsite, Shire; served as a consultant for Epi-Q, INC Research, Otsuka Pharmaceuticals, and United Biosource; and has received royalty payments (as inventor) from NYU for license of adult ADHD scales and training materials. Drs. Clemow and Durell are full-time employees and minor shareholders of Eli Lilly and Company and/or one of its subsidiaries (Eli Lilly USA, LLC). Mr. Williams is a full-time employee of PharmaNet/i3 (vendor provider of Eli Lilly), and he is a former employee of Eli Lilly. Eli Lilly USA, LLC was the commercial source that funded all aspects of the study described in this manuscript, and Eli Lilly is the patent holder and marketing sponsor of Strattera (atomoxetine). This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials, and there are no restrictions on sharing of data and/or materials associated with this study.

Figures

Figure 1. Participant disposition flow diagram.
Figure 1. Participant disposition flow diagram.

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