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.

Trial registration: ClinicalTrials.gov identifier: NCT00151983.

Key words::

• Attention-deficit/hyperactivity disorder
• Extended-release methylphenidate
• Methylphenidate transdermal system
• Stimulants

Transparency

Declaration of funding

This study was funded by Shire Development Inc., Wayne PA, USA.

Declaration of financial/other relationships

L.E.A. has disclosed that he has received research support, speaker and/or consultant fees from Shire Development, Inc., Neuropharm, Targacept, Organon, Novartis, Autism Speaks, NIMH, and the Reach Institute/Ackerman Foundation. P.H. has disclosed that he is an employee of, and holds stock in, Shire. M.M. has disclosed that he is an employee of Shire. L. B-T. has disclosed that she has received research support from several pharmaceutical companies including Shire. M.G. has disclosed that he has received research support, speaker and/or consultant fees from Shire and several other pharmaceutical companies. O.B. has disclosed that he has received research support, speaker and/or consultant fees from several pharmaceutical companies including Shire. A.P. and D.R.B. have no financial relationships to disclose.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors acknowledge the children and their families for study participation. The authors also acknowledge Laura Miesle, PharmD, of The JB Ashtin Group, Inc., Plymouth, MI, USA for assistance in the preparation of this manuscript.

Some of the data in this paper were previously presented at American Psychiatric Association, Toronto, Canada, 2006 May 24; at American College of Clinical Pharmacy, St. Louis, MO, USA, 2006 October 29; at American Academy of Child and Adolescent Psychiatry, San Diego, CA, USA, 2006 October 27; and at US Psychiatric and Mental Health, New Orleans, LA, USA, 2006 November 16.

Notes

*Daytrana is a registered trademark of Shire Pharmaceuticals Ireland Limited, Dublin, Ireland.

†Dot Matrix is a registered trademark of Noven Pharmaceuticals, Miami, FL, USA.