Dose-Response Characteristics in Adolescents with Attention-Deficit/Hyperactivity Disorder Treated with OROS® Methylphenidate in a 4-Week, Open-Label, Dose-Titration Study

Objective: The aim of this study was to evaluate dose-response characteristics in adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with once-daily OROS (R) methylphenidate (OROS (R) MPH) during the 4-week, open-label, escalating dose-titration phase of a larger multisite, placebo-controlled trial. Patient factors such as age, height, weight, and baseline symptom severity were evaluated as predictors of selected dose, as was the degree of incremental response with each successive dose escalation. Methods: Adolescents 13-18 years of age with ADHD underwent a 4-week, open-label, escalating dose-titration trial to determine the minimal effective dose (18, 36, 54, or 72 mg once daily) of OROS (R) to be used in a multiphase, placebo-controlled study (NCT00249353). Both final absolute dose and mean weight-adjusted dose were used to assess predictors of response, using a one-way analysis of variance and regression analyses. Results: The majority of subjects who did not respond at lower doses achieved response at each escalating dose level. Approximately two-thirds of subjects required a dose of 54 mg or greater to achieve improvement criteria. Minimal effective dose correlated modestly with baseline symptom severity. Age, height, and weight did not correlate with absolute dose and accounted for only a small percentage of variance in weight-based dose. Weight was not a major factor in predicting effective dose; however, using weight-adjusted rather than absolute dose proved slightly superior for modeling of adverse effects. Conclusions: Adolescents required, on average, a higher absolute dose but a lower weight-adjusted dose (mg/kg) of OROS (R) than was previously reported in children. There were few predictors of optimal dose of OROS (R) other than baseline symptom severity. The increased percentage of adolescent responders at each dose level using this clinically driven approach to titration differs from recent findings from randomized forced dose titration studies in adults with ADHD. ClinicalTrials.gov Identifier: NCT00249353