Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued attention-deficit/hyperactivity disorder symptom control and tolerability after abrupt conversion

Abstract

Objective: To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6-12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study.

Results: Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean +/- SD) scores at week 4 than at baseline (9.9 +/- 7.47 vs. 14.1 +/- 7.48; p < 0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and three discontinued because of other AEs.

Conclusions: Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself. ClinicalTrials.gov: NCT00151983.

Figures

Figure 1

Abrupt conversion study design. Week 1 was the initial effectiveness evaluation point, which assessed the accuracy and feasibility of the dose-transition schedule. Week 4 was the primary effectiveness evaluation point, the last measured change in ADHD-Rating Scale-IV total score from baseline. MPH = methylphenidate, MTS = methylphenidate transdermal system.

Figure 2

Disposition of subjects.

Figure 3

Mean ADHD-Rating Scale-IV (ADHD-RS-IV) total score in the intent-to-treat population compared with baseline. Study endpoint is defined as the last observation obtained post baseline. *p<0.0001 for paired t-test of mean change from baseline.

Figure 4

Percentage of subjects in each Clinical Global Impression-Improvement (CGI-I) and Parent Global Assessment (PGA) category at week 1 and study endpoint. Improvement or no change includes (“very much improved”, “much improved”, “minimally improved”, or “no change”). Worsened includes (“minimally worse”, “much worse”, or “very much worse”).