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 3 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. NCT NCT00151983

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies

“…Of 34 publications included in the review, three publications derived from two open-label switching studies [ 46 - 48 ] and three publications derived from one observational study [ 49 - 51 ] were identified. All studies included Concerta ® as a comparator.…”

“…Titration was based on changes in ADHD-RS-IV score and Clinical Global Impressions–Severity (CGI–S) scale score. Measures of ADHD symptoms and quality of life were obtained using ADHD-RS-IV, CPRS-R, CGI–S, CGI–I, PGA and the ADHD Impact Module-Child (AIM-C) [ 46 , 47 ].…”

Estimation of Utilities in Attention-Deficit Hyperactivity Disorder for Economic Evaluations

“…The profile of the sample (n = 171) was as follows: mean age 9.4 years (SD 1.9); 71% male; 79% White Caucasian, 12% African American, 9% other ethnicity; duration of ADHD = 3.6 years (SD 2.1); ADHD type: 77% combined, 21% inattentive, 2% hyperactive; mean ADHD-RS = 14.1 (SD 7.5); mean CPRS-R = 77.1 (SD 45.4) [see Arnold et al [25] for more details].…”

“…The utility values that had been determined for levels of CGI-S could then be used to estimate utilities for CGI-I based on the mapping function. The estimation of the mapping function was based on data from two clinical trials, [25,30] which were combined for this analysis. CGI-S values at follow-up were estimated using a linear regression of CGI-S scores (range 1-7) on ADHD-RS at baseline for the combined trials.…”

“…A thematic qualitative analysis was performed on the transcribed interview data to identify emergent themes and concepts. [24] Clinical Trial Analysis Baseline clinical trial data from a trial of a methylphenidate-based therapy [25] were analyzed to support the development of the health states. This trial included different outcomes assessments including the Clinical Global Impression-Severity (CGI-S), [26] the ADHD Rating Scale (ADHD-RS), [27] and the ADHD Impact Module-Child (AIM-C).…”