Grant Number:
K23 MH083881
PI: Tanya Froelich, MD
Collaborators: Jeffery Epstein, PhD; Robert Kahn, MD; Tracy Glauser, Floyd Sallee (University of Cincinnati); Todd Nick (University of Arkansas); Mark Stein (University of Illinois, Chicago),

Robust data show that stimulant medications reduce ADHD symptoms and impairment in most children with ADHD-combined type, who have both inattention and hyperactivity.  However, it is unclear whether stimulant medications have the same effects on children with ADHD-predominantly inattentive type, who lack hyperactivity.   Furthermore, not all children with ADHD-combined type benefit from stimulant medications, and even among those who do, there is wide variability in the most effective dose.  As a result, stimulant dosing is currently by trial and error, as no factors have been identified that reliably predict whether medications will work and how much to use.  One strategy for understanding variability in medication response is to identify genetic predictors of treatment response.  Thus, this study seeks to gain further information about stimulant medication response in children with ADHD-predominantly inattentive type, and to determine if genetic information can help to predict medication response and dosing.     

We will evaluate response to methylphenidate, the most widely prescribed stimulant, via a four week double-blind trial in which 7-11 year old participants with ADHD receive placebo and 3 different methylphenidate doses for one week each.   120 children with ADHD-predominantly inattentive type and 45 children with ADHD-combined type will be enrolled.  Parents, teachers, and the study doctor, who are all “blind” to the doses being given (since the placebo pills and different doses are all over-encapsulated so they look exactly the same), rate children’s response each week in terms of change in ADHD symptoms and side effects.  This design will allow us to address 2 specific aims: 

Aim 1:  Compare methylphenidate response in children with ADHD-predominantly inattentive type and ADHD-combined type, looking at both the amount of symptom change at the most effective dose and dose-response patterns.

Aim 2:  Determine the role of variations in dopamine- and norepinephrine-related genes on methylphenidate response in children with ADHD-predominantly inattentive type.