title: 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, 6-18years 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. joseph.gonzalez-heydrich@childrens.harvard.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Gonzalez-Heydrich
authors.forename: Jane
authors.initials: J
authors.lastname: Whitney
authors.forename: Deborah
authors.initials: D
authors.lastname: Waber
authors.forename: Peter
authors.initials: P
authors.lastname: Forbes
authors.forename: Olivia
authors.initials: O
authors.lastname: Hsin
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Alice
authors.initials: A
authors.lastname: Dodds
authors.forename: Sneha
authors.initials: S
authors.lastname: Rao
authors.forename: Christine
authors.initials: C
authors.lastname: Mrakotsky
authors.forename: Carlene
authors.initials: C
authors.lastname: Macmillan
authors.forename: David R
authors.initials: DR
authors.lastname: Demaso
authors.forename: Carl
authors.initials: C
authors.lastname: de Moor
authors.forename: Alcy
authors.initials: A
authors.lastname: Torres
authors.forename: Blaise
authors.initials: B
authors.lastname: Bourgeois
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004827:Epilepsy / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care
chemical_list: D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D008774:Methylphenidate