Executive function deficits in children with attention-deficit/hyperactivity disorder and improvement with lisdexamfetamine dimesylate in an open-label study

Abstract

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.

FIG. 1.

Mean (SD) BRIEF T scores at baseline and end of study by ADHD subtype (intention-to-treat population). At baseline and endpoint, n = 54 and 51 for the inattentive, n = 4 and 4 for the hyperactive-impulsive, n = 257 and 253 for the combined groups, respectively. Dashed line represents standardized T score of 65. T scores ≥65 have potential clinical significance. Error bars indicate SD. ADHD = attention-deficit/hyperactivity disorder; BRIEF = Behavior Rating Inventory of Executive Function; SD = standard deviation.

FIG. 2.

Mean BRIEF T score changes from baseline at end of study/early termination by history of psychiatric symptoms on medical history and by incidence of common TEAEs (intention-to-treat population). Common TEAEs were those reported by ≥5% of patients with both baseline and end-of-study BRIEF assessments (i.e., upper abdominal pain, affect lability, decreased appetite, headache, initial insomnia, insomnia, irritability, nausea, vomiting, and decreased weight). ^ap ≤ 0.0002 based on one-sample t-test versus baseline. Error bars indicate SD. TEAEs = treatment-emergent adverse events.