SAN DIEGO – In children with attention-deficit hyperactivity disorder and epilepsy, treatment with osmotic release oral system methylphenidate produced no serious adverse events, no increase in seizures, and a significant decrease in the ADHD Rating Scale scores, compared with children who took placebo.
The study, which is the largest placebo-controlled trial of its kind, supports the findings of two older studies of methylphenidate and children with epilepsy and ADHD, but it marks the first time that OROS MPH (Concerta) has been evaluated in this population, Dr. Joseph Gonzalez-Heydrich reported during a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
“Our study indicates that OROS MPH is effective in kids who have epilepsy plus ADHD who had been at least 1 month seizure free” prior to treatment, Dr. Gonzalez-Heydrich of the department of psychiatry at Children's Hospital, Boston, said in an interview. “It's also safe. We haven't seen any increase in seizures.”
Dr. Gonzalez-Heydrich and his associates randomized 27 children with ADHD and epilepsy to receive either OROS MPH at a target dose of 18, 36, or 54 mg/day, or placebo, then crossed them over to the other regimen. The mean age of the children was 11 years, and all were taking anticonvulsants. The children were seizure free for 1 month but reported having a seizure within 5 years of study enrollment.
Each child remained at the maximum dose of OROS MPH for up to 1 week before crossing over into the placebo arm of the study. Each week, the researchers recorded adverse events and administered the ADHD Rating Scale (ADHD-RS) and the Clinical Global Impressions Scale (CGI).
“Change in the ADHD-RS total, hyperactive, and inattentive scores all revealed a significant main effect of week of treatment and a significant interaction of treatment and week,” the researchers wrote in their poster. Improvement from baseline was greater during the treatment phase regardless of the dosage level.
The researchers also noted that active medication and higher dosage predicted a greater decrease in the CGI severity scores.
No adverse events were observed, and seizures occurred during the active treatment and placebo phases in two patients. In addition, one other patient experienced a seizure during the placebo phase but not during the active treatment phase.
During the treatment phase, a more robust response was seen in boys, compared with girls. That difference “may have something to do with the threshold for girls being referred for treatment” but it remains unclear, Dr. Gonzalez-Heydrich said.
He acknowledged that a key limitation of the study was its small sample size. “We need a larger study,” he said. “We'd also like to start including kids with more frequent seizures. Then you'd really have the power to tell whether the seizures are affected [by the treatment] or not.”
The study was funded by a grant from the National Institute of Mental Health. McNeil Pediatrics, which manufactures Concerta, provided the study drug and the matching placebo.
Dr. Gonzalez-Heydrich also disclosed that McNeil covered his expenses to present the work at the meeting.
During treatment, a more robust response was seen in boys than in girls. DR. GONZALEZ-HEYDRICH