Attention Deficit Disorder Medication Response Study

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.