Adaptive phase I study of OROS methylphenidate treatment of attention deficit hyperactivity disorder with epilepsy.
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.
Gonzalez-Heydrich
Joseph
J
Department of Psychiatry, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. joseph.gonzalez-heydrich@childrens.harvard.edu
Whitney
Jane
J
Waber
Deborah
D
Forbes
Peter
P
Hsin
Olivia
O
Faraone
Stephen V
SV
Dodds
Alice
A
Rao
Sneha
S
Mrakotsky
Christine
C
Macmillan
Carlene
C
Demaso
David R
DR
de Moor
Carl
C
Torres
Alcy
A
Bourgeois
Blaise
B
Biederman
Joseph
J
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
D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D008774:Methylphenidate