Project Description:
An abundance of studies attest to the efficacy of MPH for attenuating inattentive, hyperactive, and impulsive symptoms in children with ADHD. Despite its efficacy, most children with ADHD who are prescribed MPH have poor continuity of treatment for a variety of reasons, including forgetting to administer the medication and delays obtaining refills. In addition, it is an accepted clinical practice for physicians to omit MPH for periods of time, such as during the summer or on weekends (i.e., drug holidays). Since MPH discontinuation is considered to be benign, many clinicians do not employ any special procedures or inform families of any special precautions in regard to its cessation. However, increasing evidence suggests that the pharmacological effects of MPH cause lasting changes in brain neurochemistry that persist beyond medication discontinuation. Moreover, these neurobiological effects of discontinuation appear to have neurobehavioral consequences. In fact, our preliminary data suggest that MPH discontinuation results in post-discontinuation worsening in behavioral, neuropsychological, and academic functioning that is compromised to the point of being significantly worse than prior to starting medication, and these effects persist as long as 2-3 weeks after the last dose of MPH. Moreover, the magnitude of discontinuation-related worsening is comparable to, or larger than, the magnitude of benefits seen from MPH treatment. There is a critical need to better understand the breadth and magnitude of the neurobehavioral effects caused by MPH discontinuation as well as to better understand the temporal trajectory of these deleterious effects. Hence, the primary goal of the proposed research is to conduct the first randomized, doubleblind, placebo-controlled trial specifically designed to study the negative effects of MPH discontinuation at multiple time points. 180 children diagnosed with ADHD will participate across two recruitment sites. After randomization to either a MPH discontinuation, sustained MPH, or sustained placebo condition, a comprehensive multi-time point, multi-informant (parents, teachers, study staff) and multi-modal (behavior/mood/affect ratings scales, direct behavior observations, standardized testing) assessment will be used to assess a broad range of neurobehavioral outcomes across the three groups. We will examine the magnitude and time course of effects of MPH discontinuation on behavioral as well as cognitive and academic functioning in children with ADHD. Furthermore, we will examine moderators of the adverse effects of MPH discontinuation on these outcomes to aid in the identification of those who are at increased risk.
