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

Abstract

Objective: 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 have not been studied.

Methods: These post hoc analyses used data from a 10-week double-blind, placebo-controlled study of adults with ADHD and EF deficits treated with lisdexamfetamine dimesylate (30-70 mg) or placebo conducted from May 2010 to November 2010. Efficacy endpoints included change from baseline at week 10/early termination (ET) in self-report Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (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: Mediation proportions were 0.62 (indirect and total treatment effect coefficients [95% CI]: -6.85 [-9.83 to -3.86] and -11.12 [-14.88 to -7.37]) for 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 and 0.93 (indirect and total treatment effect coefficients [95% CI]: -10.34 [-14.11 to -6.57] and -11.18 [-15.80 to -6.55]) for 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.

Conclusions: Although these data suggest ADHD symptom and EF deficit improvement following lisdexamfetamine 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.

Trial registration: Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01101022.