Once-a-day concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings

Objective. Methylphenidate (MPH), the most commonly prescribed drug for att ention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces pro blems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting stimulants and preparat ions have shown effects equivalent to twice-daily dosing of MPH. This study tests the efficacy and duration of action, in natural and laboratory setti ngs, of an extended-release MPH preparation designed to last 12 hours and t herefore be equivalent to 3-times-daily dosing. Methods. Sixty-eight children with ADHD, 6 to 12 years old, participated in a within-subject, double-blind comparison of placebo, immediate-release (I R) MPH 3 times a day (tid), and Concerta, a once-daily MPH formulation. Thr ee dosing levels of medication were used: 5 mg IR MPH tid/18 mg Concerta on ce a day (qd); 10 mg IR MPH tid/36 mg Concerta qd; and 15 mg IR MPH tid/54 mg Concerta qd. All children were currently medicated with MPH at enrollmen t, and each child's dose level was based on that child's MPH dosing before the study. The doses of Concerta were selected to be comparable to the dail y doses of MPH that each child received. To achieve the ascending rate of M PH delivery determined by initial investigations to provide the necessary c ontinuous coverage, Concerta doses were 20% higher on a daily basis than a comparable tid regimen of IR MPH. Children received each medication conditi on for 7 days. The investigation was conducted in the context of a backgrou nd clinical behavioral intervention in both the natural environment and the laboratory setting. Parents received behavioral parent training and teache rs were taught to establish a school-home daily report card (DRC). A DRC is a list of individual target behaviors that represent a child's most salien t areas of impairment. Teachers set daily goals for each child's impairment targets, and parents provided rewards at home for goal attainment. Each we ekday, teachers completed the DRC, and it was used as a dependent measure o f individualized medication response. Teachers and parents also completed w eekly standardized ratings of behavior and treatment effectiveness. To eval uate the time course of medication effects, children spent 12 hours in a la boratory setting on Saturdays and medication effects were measured using pr ocedures and methods adapted from our summer treatment program. Measures of classroom behavior and academic productivity/accuracy were taken in a labo ratory classroom setting during which children completed independent math a nd reading worksheets. Measures of social behavior were taken in structured , small-group board game settings and unstructured recess settings. Measure s included behavior frequency counts, academic problems completed and accur acy, independent observations, teacher and counselor ratings, and individua lized behavioral target goals. Reports of adverse events, sleep quality, an d appetite were collected. Results. On virtually all measures in all settings, both drug conditions we re significantly different from placebo, and the 2 drugs were not different from each other. In children's regular school settings, both medications i mproved behavior as measured by teacher ratings and individualized target b ehaviors (the DRC); these effects were seen into the evening as measured by parent ratings. In the laboratory setting, effects of Concerta were equiva lent to tid MPH and lasted at least through 12 hours after dosing. Concerta was significantly superior to tid MPH on 2 parent rating scores, and when asked, more parents preferred Concerta than preferred tid IR MPH or placebo . Side effects on children's sleep and appetite were similar for the 2 prep arations. In the lab setting, both medications improved productivity and ac curacy on arithmetic seatwork assignments, disruptive and on-task behavior, and classroom rule following. Both medications improved children's rule fo llowing and negative behavior in small group board games, as well as in uns tructured recess settings. Individual target behaviors also showed signific ant improvement with medication across domains in the laboratory setting. C hildren's behavior across settings deteriorated across the laboratory day, and the primary effect of medication was to prevent this deterioration as t he day wore on. Results support the use of background behavioral treatment in clinical trials of stimulant medication, and illustrate the utility of a measure of individualized daily target goals (ie, the DRC) as an objective measure of medication response in both the laboratory and natural school s ettings. Conclusion. This investigation clearly supports the efficacy of the Concert a long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening. Effects of a single morning dose lasted throughout the school day and into the evening hours, and were present for both social behavior with peers and academic pe rformance in the classroom. Effects on multiple measures, by multiple infor mants, and in multiple settings, were similar to those of a standard prepar ation of MPH given 3 times a day. These effects lasted throughout a 12-hour period, providing coverage of school, afternoon, and evening behavior with a single morning dose. Measures of evening behavior in the laboratory sett ing included arithmetic productivity (analogous to homework), and recess se ttings (analogous to home and neighborhood recreational activities). Some p arents prefer behavioral interventions to medication for use at home, and s ome children with ADHD neither need nor tolerate medication in the evening. For those who do need a full 12 hours of medication coverage, based on the results of this study, Concerta would seem to be the choice. This study pr ovides a model for clinical trials of new psychoactive drugs for children: assessments by multiple raters, in both natural and ecologically valid labo ratory settings, across a range of domains of impairment and settings, exam ining a large number of objective, reliable measures of behavior, and in a context of ongoing behavioral treatment.