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.

Sleep disturbances in adolescents with ADHD: A systematic review and framework for future research

“…A fourth study randomly assigned adolescents with ADHD (aged 10 – 17) to receive mixed amphetamine salts or dexmethylphenidate in a double-blind, randomized, placebo-controlled, crossover, dose-response study (Santisteban, Stein, Bergmame, & Gruber, 2014). Higher doses of both medications resulted in longer actigraphic-measured SOL and shorter TST; there were no differences between medications on sleep parameters.…”

“…All of the studies reviewed in this section utilized standardized subjective or objective (actigraphy) measures of sleep and formally assessed for ADHD diagnosis (during childhood or currently) and most excluded or controlled for demographics and/or comorbidity (Santisteban et al, 2014 is the exception). However, the relatively small samples were all or mostly male and clinic- or school-referred, limiting generalizability.…”

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder

“…Both sleep onset latency and total sleep time were negatively impacted by methylphenidate administration in another study of 21 children aged 6–12 years (Corkum et al 2008). In another 8-week randomized crossover study, 37 children aged 10–17 years received extended-release dexmethylphenidate and extended-release mixed amphetamine salts (Santisteban et al 2014). Both medications decreased sleep duration as measured by actigraphy, and there was no significant difference between the two medications.…”

“…Both medications decreased sleep duration as measured by actigraphy, and there was no significant difference between the two medications. Higher doses were associated with a later sleep onset and shorter sleep duration (Santisteban et al 2014). …”

Assessment and Treatment of Attention-Deficit/Hyperactivity Disorder: Part 2

“…20 Factors that increase the risk of stimulant-induced FEATURE sleep disturbance include young age, being stimulant-naïve, and being on higher doses of stimulants. 22 Less common side effects include affective flattening, irritability, mood lability, tics, and medication "rebound," which is often reported as increased restlessness, irritability, and noncompliance when the stimulant wears off. Rebound may be a result of reappearance of ADHD symptoms as the stimulant wears off, and it is sometimes successfully treated with a small dose of a short-acting stimulant.…”