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. 2014 Sep;28(9):825-33. doi: 10.1007/s40263-014-0181-3.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Adolescent
  • Amphetamines / administration & dosage*
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Central Nervous System Stimulants / administration & dosage*
  • Child
  • Cross-Over Studies
  • Delayed-Action Preparations / administration & dosage
  • Dexmethylphenidate Hydrochloride / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Salts / administration & dosage
  • Sleep / drug effects*
  • Sleep / physiology
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome


  • Amphetamines
  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Salts
  • Dexmethylphenidate Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00393042