Cardiovascular effects of mixed amphetamine salts extended release in the treatment of school-aged children with attention-deficit/hyperactivity disorder.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Donner
Richard
R
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. donnerr@email.chop.edu
Michaels
M Alex
MA
Ambrosini
Paul J
PJ
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000661:Amphetamine / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012111:Residence Characteristics; D016037:Single-Blind Method
D018759:Adrenergic Uptake Inhibitors; D003692:Delayed-Action Preparations; D000661:Amphetamine