OBJECTIVE-To pilot a randomized controlled trial of OROS-Methylphenidate (MPH) to treat ADHD plus epilepsy.METHOD-Thirty-three patients, 6-18 years, taking antiepileptic drugs and with a last seizure 1-60 months prior were assigned to a maximum daily dose of 18, 36, or 54mg of OROS-MPH in a double-blind placebo-controlled crossover trial. In the past year, Dr. Stephen Faraone has received consulting fees and has been on Advisory Boards for Eli Lilly, McNeil and Shire and has received research support from Eli Lilly, Pfizer, Shire and the National Institutes of Health. In previous years, Dr. Faraone has received consulting fees or has been on Advisory Boards or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfizer and the National Institutes of Health. Dr. Joseph Biederman is currently receiving research support from the following sources: Alza, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck, Organon, Otsuka, Shire, NIMH, and NICHD. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, he has received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth. Dr. Blaise Bourgeois has received grant/research support from Eisai, Ovation and UCB Pharma. In the past two years, he has also received consulting fees from Genzyme and Bayer Material Science.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. RESULTS-There were no serious adverse events and no carry over effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than 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 need further study. NIH Public AccessCONCLUSION-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 re...

Background-ADHD coexisting with epilepsy is poorly understood, thus we compared the clinical correlates and psychiatric comorbidities in 36 children with epilepsy and ADHD, aged 6 to 17 years enrolled in an ADHD treatment trial, to those reported in the literature on children with ADHD without epilepsy. Methods-Measures included the Kiddie Schedule for Affective Disorders and Schizophrenia forSchool-Age Children (KSADS), the Wechsler Abbreviated Scale of Intelligence (WASI), and the Scales for Independent Behavior-Revised (SIB-R).Results-Mean IQ was 86±19, and SIB-R Standard Score was 72±26. The ADHD-Combined subtype, composed of both inattentive and hyperactive symptoms, was most frequent (58%). Sixtyone percent exhibited a comorbid disorder, including anxiety disorders (36%), and Oppositional Defiant Disorder (31%).Conclusions-Comorbidity in ADHD with epilepsy is similar to that of ADHD without epilepsy reported in the literature. These preliminary data argue that the pathophysiology of ADHD has common components in both populations.

Objective: In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history. Methods: Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 nonreferred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews. Results: No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers. Conclusions: Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.