Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder

• Published in: Journal of child and adolescent psychopharmacology Vol. 25; no. 10; pp. 799 - 809
• Main Authors: Upadhyaya, Himanshu, Kratochvil, Christopher, Ghuman, Jaswinder, Camporeale, Angelo, Lipsius, Sarah, D'Souza, Deborah, Tanaka, Yoko
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.12.2015
• Subjects: Adrenergic Uptake Inhibitors - adverse effects; Adrenergic Uptake Inhibitors - therapeutic use; Age Factors; Analysis; Atomoxetine Hydrochloride - adverse effects; Atomoxetine Hydrochloride - therapeutic use; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Child; Child, Preschool; Children & youth; Double-Blind Method; Female; Humans; Male; Original; Randomized Controlled Trials as Topic; Safety
• ISSN: 1044-5463; 1557-8992; 1557-8992
• DOI: 10.1089/cap.2014.0001

This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4-5-year-old patients and 6-7-year-old patients, whereas a weight increase was seen only in the 6-7-year-old patients. Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.