Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in the Treatment of School-Aged Children with Attention-Deficit/Hyperactivity Disorder

Abstract

The cardiovascular safety of mixed amphetamine salts extended release (MAS XR) was evaluated in 2968 children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD). In this prospective, open-label, noncomparative, community-based study, subjects whose symptoms of ADHD were well controlled with stimulant medication maintained their established treatment regimens for 2 weeks before enrollment into the current study. Subjects' regimens were then converted to an approximately equivalent once-daily dose of MAS XR 10, 20, or 30 mg/d according to a medication-conversion algorithm, which could be adjusted to 40 mg/d for optimal efficacy and tolerability. Systolic blood pressure (SBP), diastolic BP (DBP), and pulse were measured at each study visit. Twelve-lead electrocardiography was performed at screening and at the end of the extension phase or early termination. No clinically significant changes in BP or pulse were observed. Although one subject experienced a QT-prolongation interval > 25%, no clinically significant prolongation in the mean QT interval was seen. Approximately 2.5% of subjects demonstrated two consecutive SBP or DBP values > 95th percentile for age, sex, and height, and 3.6% of subjects' pulse increased by > or = 25 to > or = 110 beats per minute. No serious cardiovascular adverse events or deaths occurred. In addition to demonstrated efficacy and safety, the cardiovascular profile of MAS XR showed generally small divergences from age-specific population norms that pose very limited risk in this patient population.