Executive Function Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Improvement with Lisdexamfetamine Dimesylate in an Open-Label Study

Objective: To assess the effects of lisdexamfetamine dimesylate (LDX) on executive function (EF) behaviors in children with attention-deficit/hyperactivity disorder (ADHD). Methods: This observational, open-label, 7-week, dose-optimization study of LDX (20-70 mg/day) in children with ADHD evaluated efficacy with the ADHD Rating Scale IV; safety measures included adverse events (AEs). EF was assessed with the Behavior Rating Inventory of Executive Function (BRIEF). Post hoc analyses examined BRIEF scores by sex, ADHD subtype, comorbid psychiatric symptoms, and common treatment-emergent AEs (TEAEs). ADHD Rating Scale IV scores were assessed in subjects categorized by baseline BRIEF global executive composite T scores with clinically significant (>= 65) or not clinically significant (<65) impairment in EF. Results: Mean (standard deviation) change from baseline to endpoint for BRIEF of -17.9 (12.5) for Global Executive Composite, -15.4 (12.6) for Behavioral Regulation Index, and -17.6 (12.3) for Metacognition Index demonstrated improvement with LDX (pooled doses; p<0.0001 for all). Improvements in BRIEF scores were seen regardless of sex, ADHD subtype, comorbid psychiatric symptoms, common TEAEs, or baseline EF impairment category. TEAEs included decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia. Conclusions: Improvements were demonstrated in EF behaviors and ADHD symptoms with LDX. LDX safety profile was consistent with long-acting stimulant use.