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A Randomized, Double-Blind, Crossover Study of Once-Daily Dexmethylphenidate in Children with Attention-Deficit Hyperactivity Disorder

Rapid Onset of Effect

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Abstract

Background: Long-acting methylphenidate formulations provide control of attention-deficit hyperactivity disorder (ADHD) symptoms for up to 12 hours; however, not all formulations have rapid onset of therapeutic effect, which is essential for providing symptom control during morning hours. The primary objective of this randomized, double-blind, crossover study was to assess the efficacy of dexmethylphenidate extended release (ER) versus placebo by measuring the change from pre-dose to 0.5 hours post-dose on the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scale.

Methods: Eighty-six children (6–12 years) with ADHD diagnosed using the DSM-IV criteria were randomized to receive dexmethylphenidate ER 20 mg/day or placebo, sequentially, for 7 days, with the final dose administered in a laboratory classroom setting on day 7 of each treatment period. The primary efficacy comparison was change in the SKAMP-Combined score from pre-dose to 0.5 hours post-dose, with additional secondary assessments at 1, 2, 4, 6 and 8 hours post-dose. Secondary efficacy measures included change from pre-dose at all timepoints in the SKAMP-Attention and SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores, and change from baseline on the Conners’ ADHD/DSM-IV Scale for Parents (CADS-P). In an exploratory analysis, a daily diary card was completed by parents on the children’s in-home behaviour before school. Safety was assessed by occurrence of adverse events, monitoring of vital signs and interpretation of ECGs.

Results: Significant improvements were noted at 0.5 hours and at all timepoints post-dose throughout the 8-hour laboratory classroom day for dexmethylphenidate ER vs placebo in the primary outcome measure of the SKAMP-Combined scores (p < 0.001), as well as SKAMP-Attention, SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores (p < 0.05). The changes from baseline in CADS-P scores were significantly greater with dexmethylphenidate ER than placebo (−16.382 vs −4.622; p < 0.001). Responses to all diary questions indicated significant improvement with dexmethylphenidate ER treatment versus placebo (all p < 0.001). The most common adverse events were abdominal pain (dexmethylphenidate ER 3.5%; placebo 4.7%), headache (dexmethylphenidate ER 3.5%; placebo 2.3%) and increased appetite (dexmethylphenidate ER 0%; placebo 3.5%).

Conclusion: Compared with placebo, once-daily dexmethylphenidate ER 20 mg provided rapid and significant improvement at 0.5 hours post-dose in attention, deportment and academic performance, which was sustained for 8 hours post-dose. Overall, once-daily dexmethylphenidate ER 20 mg was well tolerated. In an analysis of parental assessment of diary responses, children appeared more organized, and morning preparation for school was smoother and less frustrating with once-daily dexmethylphenidate ER compared with placebo.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This study was funded by Novartis Pharmaceuticals Corporation and reports the following involvement: design and conduct of the study; collection, management, analysis and interpretation of data; and preparation, review and approval of the manuscript.

Matthew Brams, MD, has been a speaker, consultant and advisory board member for Novartis and Shire, and has received grant-research support from Novartis, Shire and Eli Lilly.

Rafael Muniz, MD, is an employee of Novartis Pharmaceuticals Corporation and owns stock options as part of his employment.

Ann Childress, MD, has been a speaker, consultant and advisory board member for Novartis and Shire; speaker for Bristol-Myers Squibb; and received grant-research support from Novartis, Shire, Abbott, Astra-Zeneca, Somerset, Eli Lilly, Johnson & Johnson, Neuropharm and Bristol-Meyers Squibb.

John Giblin, MD, FAAP, has been a speaker and consultant for Novartis and Shire; and has received grant-research support from Novartis, Shire, Abbott, Esai, GlaxoSmithKline, Johnson & Johnson, Ortho-McNeill, Sanofi-Aventis, Cephalon, New River Pharmaceuticals, Wyeth and Pfizer.

Alice Mao, MD, has been a speaker for Novartis, Eli Lilly, Bristol-Meyers Squibb, Astra-Zeneca, Sepracor and Shire; consultant for Eli Lilly, Novartis, and Shire; and receives grant-research support from Novartis.

John Turnbow, MD, has been a speaker and advisory board member for Novartis, UCB Pharma and Shire; receives grant-research support from Novartis, Shire and Sanofi-Aventis; and has had past grant-research support from Celltech (now UCB Pharma).

Mary Borrello, RN, is an employee of Novartis and owns stock options as part of her employment.

Kevin McCague, MA, is an employee of Novartis and owns stock options as part of his employment.

Frank Lopez, MD, has been a speaker, consultant and advisory board member for Novartis, Shire and Eli Lilly; and receives research grants from Noven, Novartis, Shire, New River Pharmaceuticals, Celltech-Medeva, Bristol-Myers Squibb, Wyeth, GlaxoSmithKline and Cephalon.

Raul Silva, MD, reports no conflicts of interest since 15 December 2006; prior to this date he was a speaker for Novartis, AstraZeneca and Janssen and received grant-research support from Novartis, Forest and Celgene.

The authors gratefully acknowledge Bonnie Brien of Novartis Pharmaceuticals Corporation who assisted in the preparation of a first draft of this article based on an author-approved outline, and also assisted in implementing author revisions.

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Authors and Affiliations

  1. Baylor College of Medicine, 500 Wescott Drive, Suite 520, Houston, Texas, 77019, USA

    Matthew Brams & Alice Mao

  2. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

    Rafael Muniz, Mary Borrello & Kevin McCague

  3. Center for Psychiatry and Behavioral Medicine Inc., Las Vegas, Nevada, USA

    Ann Childress

  4. Clinical Study Centers, LLC, Little Rock, Arkansas, USA

    John Giblin

  5. Westex Clinical Investigations, Lubbock, Texas, USA

    John Turnbow

  6. Children’s Developmental Center, Winter Park, Florida, USA

    Frank A. Lopez

  7. New York University Child Study Center, New York, New York, USA

    Raul Silva

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  1. Matthew Brams
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  9. Frank A. Lopez
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Correspondence to Matthew Brams.

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Brams, M., Muniz, R., Childress, A. et al. A Randomized, Double-Blind, Crossover Study of Once-Daily Dexmethylphenidate in Children with Attention-Deficit Hyperactivity Disorder. CNS Drugs 22, 693–704 (2008). https://doi.org/10.2165/00023210-200822080-00006

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  • DOI: https://doi.org/10.2165/00023210-200822080-00006

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