Adaptive phase I study of OROS methylphenidate treatment of attention deficit hyperactivity disorder with epilepsy

Abstract Objective The goal of this study was to pilot a randomized controlled trial of OROS methylphenidate (OROS-MPH) to treat attention deficit hyperactivity disorder (ADHD) plus epilepsy. Methods Thirty-three patients, 6–18 years of age, taking antiepileptic drugs and with a last seizure 1–60 months prior were assigned to a maximum daily dose of 18, 36, or 54 mg of OROS-MPH in a double-blind placebo-controlled crossover trial. Results There were no serious adverse events and no carryover effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than did placebo treatment. There were too few seizures during the active (5) and placebo arms (3) to confidently assess seizure risk; however, considering exposure time, we observed an increased daily risk of seizures with increasing dose of OROS-MPH, suggesting that potential safety concerns require further study. Conclusion A larger study to assess the effect of OROS-MPH on seizure risk is needed. A crossover design including subjects with frequent seizures could maximize power and address high patient heterogeneity and recruitment difficulties.