Relationship Between ADHD Symptom and Executive Function Improvement in Adult ADHD in SHP465 Mixed Amphetamine Salts Extended-Release Clinical Trials

Adult attention-deficit/hyperactivity disorder (ADHD) is associated with impaired executive function (EF). This post hoc analysis examines relationships between changes in ADHD symptoms and EF, as measured by the ADHD-Rating Scale-IV (ADHD-RS-IV) and Brown Attention-Deficit Disorder Scale (BADDS), respectively, following SHP465 mixed amphetamine salts (MAS) extended-release treatment. Data from 2 studies in adults with DSM-IV-TR–defined ADHD were used. In a 7-week dose-optimization study, adults with baseline ADHD-RS-IV total score ≥24 were randomized to SHP465 MAS (12.5–75 mg) or placebo. In a 6-week fixed-dose study, adults with baseline ADHD-RS-IV total score ≥32 were randomized to SHP465 MAS (25, 50, or 75 mg) or placebo. Pearson correlations examined relationships between changes from baseline to end of study (EOS; last nonmissing postbaseline assessment) in ADHD-RS-IV and BADDS scores in the intent-to-treat (ITT) populations. The ITT populations of the dose-optimization and fixed-dose studies, respectively, included 132 and 103 placebo participants and 136 and 302 SHP465 MAS participants. Changes from baseline to EOS in ADHD-RS-IV total score were positively correlated with BADDS total score changes in the dose-optimization study (Pearson correlation coefficients [placebo; SHP465 MAS]: 0.7054; 0.7252) and fixed-dose study (Pearson correlation coefficients [placebo; SHP465 MAS]: 0.7539; 0.7439). ADHD-RS-IV subscale score changes were also positively correlated with BADDS total score changes in both studies (Pearson correlation coefficient range: 0.2447 to 0.7699). In conclusion, these post hoc analyses indicate that ADHD symptom and EF improvement was correlated in SHP465 MAS studies in adults with ADHD, suggesting changes in these domains may be interdependent.