Objective: This pilot, uncontrolled, open-label study evaluated the safety/tolerability and potential effectiveness of OROS-methylphenidate (OROS-MPH) in adult attention deficit hyperactivity disorder (ADHD).
Methods: Adults with DSM-IV-defined ADHD were enrolled in this 38-day study. Retrospective childhood diagnosis was made using the Wender Utah Rating Scale. Eligible patients required a baseline Conners Adult ADHD Rating Scale (CAARS) score > or = 24, Clinical Global Impression of Severity (CGI-S) score > or = 4 (at least moderate illness), and Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 16. Safety/tolerability measurements included adverse event reporting, vital signs, electrocardiograms (ECGs), weight, physical examination. Primary effectiveness evaluated changes in CAARS scores. Secondary effectiveness parameters included executive function.
Results: Thirty-two patients formed the safety analysis; however, 30 comprised the effectiveness analysis since two patients did not meet diagnostic inclusion criteria. No serious adverse events were reported and there were no early withdrawals due to adverse events. There were no clinically significant changes in endpoint ECGs, physical examination, or blood pressure. Mean pulse rate increased by 5.9 beats/min (p = 0.003) and mean body weight decreased by 2.2 kg at endpoint (p < 0.0001). Total CAARS scores decreased significantly at endpoint as well as the inattention (p < 0.0001) and hyperactivity/impulsivity symptom subscales (p < 0.0001) separately. Statistically significant improvements were observed in executive function and all other secondary measures, including the CAARS self report, CGI-S/CGI-I, Subject Satisfaction with treatment and the Sheehan Disability Scale (SDS). Mean dose of OROS-MPH = 52.3 +/- 14.0 mg. Modal dose = 54 mg. Study limitations include: the lack of placebo control in the study design leading to potential observer bias, the exclusion of adults with unstable psychiatric and other medical conditions which is less reflective of clinical practice, and the short study duration.
Conclusions: This uncontrolled, open-label trial suggests that OROS-MPH is well tolerated, providing core symptom control with the added benefit of improving executive function. However, future larger, randomized, controlled trials are required.