Effect of extended-release dexmethylphenidate and mixed amphetamine salts on sleep: a double-blind, randomized, crossover study in youth with attention-deficit hyperactivity disorder

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.

Figures

Fig. 1

Example of a treatment schedule. Each treatment modality lasts for 1 week, for a total of 8 weeks. MAS mixed amphetamine salts, d-MPH dexmethylphenidate

Fig. 2

Sleep duration for MAS and d-MPH at all doses. Mean sleep duration decreases with higher doses for both medications. There are significant differences in mean duration during both placebo (asterisk) and 10-mg treatment (double asterisk) compared with 20 and 30 mg treatment (p<0.05). MAS mixed amphetamine salts, d-MPH dexmethylphenidate

Fig. 3

Sleep schedule: sleep start time for MAS and d-MPH at all doses. Mean sleep start time occurs later with higher doses for both medications. There are significant differences in mean sleep start time during placebo compared with 20- and 30-mg treatment (p<0.05) [asterisk]. There was also a significant difference between 10-mg treatment and 30-mg treatment (p<0.05) [double asterisk]. MAS mixed amphetamine salts, d-MPH dexmethylphenidate