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Effect of Extended-Release Dexmethylphenidate and Mixed Amphetamine Salts on Sleep: A Double-Blind, Randomized, Crossover Study in Youth with Attention-Deficit Hyperactivity Disorder

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Abstract

Objective

We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep.

Methods

This was an 8-week, double-blind, placebo-controlled, randomized, two period, crossover study of youth with attention-deficit hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children–Present and Lifetime version (K-SADS-PL). Children aged 10–17 years were recruited from clinical practice, colleague referrals, and flyers. Participants were randomized to initially receive either d-MPH or MAS. During each 4-week drug period, children received three dose levels (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active medication in a randomized fashion during 1 week of the study. After 4 weeks, participants were switched to the alternative medication for another 4 weeks of treatment. The main outcome measure was sleep duration as measured by actigraphy. Children, parents, and researchers were blinded to drug, dose, and placebo status.

Results

Sixty-five participants met the inclusion criteria and were enrolled in the study. Of these, 37 participants with sufficient sleep data for analysis were included. Sleep schedule measures showed a significant effect for dose on sleep start time (F(1,36) = 6.284; p < 0.05), with a significantly later sleep start time when children were receiving 20- or 30-mg doses, compared with placebo (p < 0.05). A significant dose effect was found on actual sleep duration (F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo (p < 0.05). There were no significant differences on sleep duration or sleep schedule between the two stimulant medications. The trial is complete and closed to follow-up.

Conclusions

Higher stimulant doses were associated with reduced sleep duration and later sleep start times, regardless of medication class.

Trial registration

ClinicalTrials.gov: NCT00393042.

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Acknowledgments

This study was sponsored by Novartis Pharmaceuticals, with additional support provided by the University of Illinois at Chicago Center for Clinical and Translational Science, award number UL1RR029879 from the National Center for Research Resources.

Mark A. Stein is a consultant for Novartis Pharmaceuticals, Alcobra Pharma, and Genco Pharma. He also receives research funding from Shire Plc and Pfizer.

Reut Gruber has no conflicts of interest to report.

Jose Arturo Santisteban received funding from the Mexican National Council for Science and Technology. He has no conflicts of interest to report.

Lana Bergmame has no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Verdun, Montreal, QC, H4H 1R3, Canada

    J. A. Santisteban & R. Gruber

  2. Attention, Behavior and Sleep Laboratory, Douglas Mental Health University Institute, Montreal, QC, Canada

    J. A. Santisteban, L. Bergmame & R. Gruber

  3. Seattle Children’s Hospital, University of Washington, Seattle, WA, USA

    M. A. Stein

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  1. J. A. Santisteban
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Correspondence to R. Gruber.

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Santisteban, J.A., Stein, M.A., Bergmame, L. et al. Effect of Extended-Release Dexmethylphenidate and Mixed Amphetamine Salts on Sleep: A Double-Blind, Randomized, Crossover Study in Youth with Attention-Deficit Hyperactivity Disorder. CNS Drugs 28, 825–833 (2014). https://doi.org/10.1007/s40263-014-0181-3

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