Attention Deficit Disorder Medication Response Study

Overview

This study evaluates how children with Attention Deficit Disorder without Hyperactivity (ADD) respond to medication, and if their response is different from children who have problems with both hyperactivity and inattention. In order to do this, children ages 7-11 whose primary difficulty is with attention problems and who have never been on behavioral or psychiatric medications are being recruited. Once enrolled, children will try one week each of 3 different doses of methylphenidate, the most commonly prescribed Attention Deficit, Hyperactivity Disorder (ADHD) medication, as well as placebo. Children will be randomly assigned to one of six possible medication dose and placebo titration schedules, but the study doctor, family, and teacher will not know which dose (if any) children are receiving for a given week. Each week, behavioral and side effect ratings will be completed by both the child's parent and teacher, and the family will meet with the study doctor for a physical examination and to discuss how each week went. Some children will also have neuropsychological testing to determine how methylphenidate influences their working memory, sustained attention, and ability to inhibit (stop) inappropriate responses. All data will be analyzed to decide which medication dose the child responded to best and further recommendations for treatment will be given. Ultimately, this study aims to improve understanding of how children with ADHD-Primarily Inattentive Type respond to stimulant medications by * determining whether these children experience a diminished response to methylphenidate compared to children with both hyperactivity and inattention * determining whether certain genetic and environmental factors play a role in this response. Findings from this study will be used to help streamline the identification of the most effective doses of medication for children with ADHD-Primarily Inattentive Type.

Robust data indicate that stimulant medications reduce ADHD symptoms and impairment, but it is unclear whether their efficacy generalizes across the ADHD subtypes. Although predominately inattentive type (PIT) is the most prevalent ADHD subtype in U.S. population-based studies, few studies have specifically examined response to stimulants in this subtype. Instead, medication guidelines for PIT have largely been extrapolated from studies enrolling all or mostly ADHD-combined type (CT). Thus, this application seeks to improve understanding of stimulant medication response and its predictors in children with PIT. We will evaluate participants' response to methylphenidate (MPH), the most widely prescribed stimulant, via a prospective, double-blind, placebo-controlled crossover trial with 3 dose conditions. Our first specific aim is to examine MPH medication and dose response in children with PIT (n=120) and CT (n=45) to test the hypotheses that participants with PIT have a diminished MPH response and derive less benefit from higher doses compared to those with CT. Since only one prior study has examined genetic predictors of MPH response variability within PIT-only samples, our second specific aim (exploratory) is to determine the potential role of genetic polymorphisms (e.g., those in DAT1, DRD4, NET, ADRA2A, COMT, SNAP25, CES1, GRM7, LPHN3) on MPH response in children with PIT (n=120), examining both symptom change with MPH and MPH dose response curves. If we identify significant differences in MPH response between the subtypes, our findings may guide clinical practice by suggesting more effective medication strategies (such as different dosing schedules) for children with PIT. In addition, this study may yield pharmacogenetic findings that, in the future, could enable physicians to tailor individual treatment plans for children with PIT, ameliorating the current prolonged and expensive practice of prescribing by trial and error.