This application is for a three year continuation of an investigation to study the clinical efficacy and effects on attentional processes of sustained-release methylphenidate (Ritalin-SR). The current research has shown that Ritalin-SR has equal clinical efficacy and dosage equivalency as the standard, short-acting Ritalin preparation (Ritalin-SA). The continuation study will serve to replicate the findings of Ritalin-SR's efficacy in a new population of school age children with Attention Deficit Disorder with Hyperactivity (ADDH) by comparing it to standard Ritalin, but over a longer course of time.
The aims are (1) to document the afternoon clinical response to Ritalin-SR over a 3 month treatment period, and (2) to establish the relative efficacy between sustained release Ritalin preparation and the standard Ritalin-SA, and (3) to study possible tolerance phenomena for Ritalin-SR by monitoring the pharmacokinetic, attentional, cognitive, and behavioral responses to the two preparations using a double-blind, across-subjects parallel design. A single Ritalin- SR daily dose, either 20 mg. or 40 mg. (determined by subject weight) will be used in one group, while twice-per-day dosing of Ritalin-SA, either 20 or 40 mg (determined by subject weight) will be used in the other group. For this continuation study, we propose to recruit a sample of 60, 8-12 year old, hyperactive males who have not been treated previously with stimulants. The 16 week protocol begins with a two week period to determine responsiveness to Ritalin-SA and to eliminate placebo responders. A 2 day placebo-controlled washout occurs next. Then the patients are randomly (paired matched by age) assigned to one of three 6 week treatments: 20 males will be placed back on a weight-adjusted dose of Ritalin- SR, 20 males will be placed on a weight-adjusted dose of Ritalin- SA, 20 males will be on placebo (""""""""placebo control""""""""). Dependent variables to be tracked include global teacher's ratings, home hyperactivity ratings, side effects measures (SAFTEE forms), Methylphenidate and Ritalin-SA plasma levels and laboratory measures (Continuous Performance Test, Perdue, Paired Associates Task, Gardner Steadiness Task, Playroom Observation, and Actigraph) for three study phases, placebo, on-drug one week and on-drug 3 months. Neuroendocrine measures of Human Growth Hormone and Prolactin will be collected to assess possible receptor changes. Data analysis will utilize multivariate analysis of variance in a repeated measures design to compare within- group and within-subjects behavioral, cognitive, and attentional responses.
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