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

Epilepsy Behav. 2010 Jul;18(3):229-37. doi: 10.1016/j.yebeh.2010.02.022. Epub 2010 May 21.

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, 6-18years of age, taking antiepileptic drugs and with a last seizure 1-60months prior were assigned to a maximum daily dose of 18, 36, or 54mg 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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anticonvulsants / blood
  • Anticonvulsants / therapeutic use
  • Attention Deficit Disorder with Hyperactivity / complications*
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Confidence Intervals
  • Cross-Over Studies
  • Double-Blind Method
  • Epilepsy / blood
  • Epilepsy / complications*
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Male
  • Methylphenidate / therapeutic use*
  • Outcome Assessment, Health Care

Substances

  • Anticonvulsants
  • Central Nervous System Stimulants
  • Methylphenidate