A Post Hoc Analysis of Relationships Between Executive Function Improvement and ADHD Symptom Improvement With Lisdexamfetamine Dimesylate in Adults With ADHD and Executive Function Deficits

Background: Executive function (EF) deficits are not generally considered synonymous with attention-deficit/hyperactivity disorder (ADHD). Evidence suggests stimulants improve ADHD symptoms and EF deficits in adults with ADHD, but the relationships between improvements in these domains after stimulant treatment have not been studied.

Methods: These post hoc analyses used data from a 10-week study of adults with ADHD and EF deficits treated with dose-optimized lisdexamfetamine dimesylate (LDX; 30–70 mg) or placebo. Efficacy endpoints included change from baseline at week 10/early termination (ET) in self-report Behavior Rating Inventory of Executive Function–Adult Version Global Executive Composite (BRIEF-A GEC) T-score and ADHD-Rating Scale with Adult Prompts total score (ADHD-RS-AP-TS). Relationships between ADHD symptom and EF changes were examined using recursive path analyses.

Results: The mediation proportion of the self-report BRIEF-A GEC T-score change from baseline at week 10/ET on ADHD-RS-AP-TS change from baseline at week 10/ET was 0.62 (indirect and total treatment effect coefficients [95% CI]: –6.85 [–9.83, –3.86] and –11.12 [–14.88, –7.37]) and of the ADHD-RS-AP-TS change from baseline at week 10/ET on self-report BRIEF-A GEC T-score change from baseline at week 10/ET was 0.93 (indirect and total treatment effect coefficients [95% CI]: –10.34 [–14.11, –6.57] and –11.18 [–15.80, –6.55]).

Conclusions: Although these data suggest ADHD symptom and EF deficit improvement following LDX treatment are interdependent, it is advantageous to use measures like the BRIEF-A to assess stimulant effects on the wide range of EF deficits associated with ADHD that are not captured by the ADHD-RS-AP alone.