Short- and long-term cardiovascular effects of mixed amphetamine salts extended-release in adolescents with ADHD

Objective: Assess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13-17 years of age) with attention-deficit/hyperactivity disorder (ADHD). Methods: Biood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR (10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study. Findings: Changes in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=. 0252) and pulse (4 A bpm; P<.0001) were statistically, but not clinically, significant; diastolic BP was not significantly changed (0.6 mm Hg). A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events. Conclusion: Cardiovascuiar effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.