Are stimulants effective in the treatment of executive function deficits? Results from a randomized double blind study of OROS-methylphenidate in adults with ADHD

The objective of this study was to evaluate the association between executive function deficits (EFDs) and response to methylphenidate treatment in ADHD in adults. We conducted a 6-week, parallel design, randomized, placebo controlled study in adults with DSM-IV ADHD. Our psychometric index of executive function used standardized neuropsychological testing. We assessed behaviors reflective of EFDs using the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A). Subjects with available measures of executive functioning (OROS-MPH N=40; Placebo N=47) were included for analysis. There was no difference in the percent of subjects completing the 6-week acute efficacy Phase I of the trial (100% (N=40) vs. 98% (N=46), p=0.4). The mean daily dose at Phase I endpoint was 84.6 +/- 31.6 mg (1.04 +/- 0.29 mg/kg) OROS-MPH and 100.5 +/- 21.9 mg (1.20 +/- 0.11 mg/kg) placebo (p=0.0007). Based on the neuropsychological testing at the baseline assessment, 40% of the ADHD subjects (N=35/87) were considered to have EFDs but 93% (N=81) of subjects had >= 2 BRIEF-A clinical scale T-scores >65. Regardless of the definition used, however, EFDs did not impact the clinical response to OROS-MPH. This randomized clinical trial showed that executive function deficits do not moderate the response to methylphenidate and measures of executive function deficits are not associated with response to OROS-MPH. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.