Original ContributionsExecutive Function in Adults With Attention-Deficit/Hyperactivity Disorder During Treatment With Atomoxetine in a Randomized, Placebo-Controlled, Withdrawal StudyAdler, Lenard MD*†; Tanaka, Yoko PhD‡; Williams, David MSc§; Trzepacz, Paula T. MD‡∥¶#; Goto, Taro MD, PhD‡; Allen, Albert J. MD, PhD‡; Escobar, Rodrigo MD**; Upadhyaya, Himanshu P. MBBS, MS‡ Author Information From the *New York University School of Medicine; and †New York VA Harbor Healthcare System, New York, NY; ‡Eli Lilly and Company, Neuroscience, Indianapolis, IN; §inVentiv Health Clinical, LLC, Ann Arbor, MI; ∥University of Mississippi Medical School, Jackson, MS; ¶Tufts University School of Medicine, Boston, MA; #Indiana University School of Medicine, Indianapolis, IN; and **Lilly Research Laboratories, Kobe, Japan. Received January 18, 2013; accepted after revision February 12, 2014. Reprints: Himanshu P. Upadhyaya, MBBS, MS, Eli Lilly and Company, LLC, Mail Code 1542, Indianapolis, IN 46285 (e-mail: [email protected]). A part of the data was disclosed previously at the 28th Collegium Internationale Neuro-Psychopharmacologicum World Congress of Neuropsychopharmacology, Stockholm, Sweden, June 3 to 7, 2012. Supplemental digital contents are available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com). Journal of Clinical Psychopharmacology 34(4):p 461-466, August 2014. | DOI: 10.1097/JCP.0000000000000138 Buy SDC Metrics Abstract We assessed the executive function in adults with attention-deficit/hyperactivity disorder (ADHD) during atomoxetine treatment in a randomized withdrawal trial. Responders (Conners’ ADHD Rating Scale–Investigator Rated: Screening Version [adult prompts] ≥30% reduction from baseline and Clinical Global Impression Scale–ADHD Severity score ≤3) to open-label atomoxetine (40–100 mg/d, 12 weeks) entered a 37-week double-blind maintenance period. Patients who maintained response (double-blind atomoxetine for 12 weeks) were randomized 1:1 to atomoxetine (80–100 mg/d, n = 266) or placebo (n = 258) for 25 weeks (total duration, 1 year). Patients and investigators were blinded to response criteria and randomization timing. Change in executive function was assessed with the Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) Self-Report and Informant T scores from the randomization to the last-observation-carried-forward postrandomization week 25 (after week 17). Of the enrolled patients (n = 2017; mean age, 33.2 years; male, 58.7%), 524 responders were randomized. During open-label atomoxetine, subscales and individual items on both BRIEF-A questionnaires showed significant improvement (P < 0.001). After randomization, the following T scores improved significantly (P ≤ 0.05) with patients in the atomoxetine group versus those in the placebo group: global executive composite, behavioral regulation, and metacognition indices; plan/organize, working memory, inhibit, task monitor and shift (both BRIEF-A questionnaires), emotional control and organization of materials (BRIEF-A Informant), and initiate (BRIEF-A Self-Report). Atomoxetine significantly improved the executive function compared with placebo, which was maintained for 25 weeks or more; the executive function of patients in the placebo group worsened but did not return to baseline levels after randomization. © 2014 by Lippincott Williams & Wilkins.