Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts

Abstract

Objective: To compare the dose effects of long-acting extended-release dexmethylphenidate (ER d-MPH) and ER mixed amphetamine salts (ER MAS) on attention-deficit/hyperactivity disorder (ADHD) symptom dimensions, global and specific impairments, and common adverse events associated with stimulants.

Methods: Fifty-six children and adolescents with ADHD participated in an 8-week, double-blind, crossover study comparing ER d-MPH (10, 20, 25-30 mg) and ER MAS (10, 20, 25-30) with a week of randomized placebo within each drug period. Efficacy was assessed with the ADHD Rating Scale-IV (ADHD-RS-IV), whereas global and specific domains of impairment were assessed with the Clinical Global Impressions Severity and Improvement Scales and the parent-completed Weiss Functional Impairment Scale, respectively. Insomnia and decreased appetite, common stimulant-related adverse events, were measured with the parent-completed Stimulant Side Effects Rating Scale.

Results: Both ER d-MPH and ER MAS were associated with significant reductions in ADHD symptoms. Improvement in Total ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with increasing dose, whereas improvements in Inattentive symptoms were only moderately associated with dose. About 80% demonstrated reliable change on ADHD-RS-IV at the highest dose level of ER MAS compared with 79% when receiving ER d-MPH. Decreased appetite and insomnia were more common at higher dose levels for both stimulants. Approximately 43% of the responders were preferential responders to only one of the stimulant formulations.

Conclusions: Dose level, rather than stimulant class, was strongly related to medication response.

Figures

FIG. 1.

Patient disposition. ADHD=attention-deficit/hyperactivity disorder; EKG=electrocardiogram.

FIG. 2.

Effects of extended release of mixed amphetamine salts and extended release dexmethylphenidate on ADHD Rating Scale Total Score (ADHD-RS) by dose. ER, extended release; d-MPH, dexmethyphenidate; MAS, mixed amphetamine salts.