Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD

Objective: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. Methods: 223 otherwise healthy adults (>= 18 years of age) with ADHD combined subtype were exposed to :524 months of MAS XR (20-60 mg/day). Resting sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) and pulse were measured at baseline and weekly, then monthly during long-term treatment. Twelve-lead electrocardiograms were obtained at screening/baseline, weekly, then at 3- and 6-month intervals up to 24 months. Findings: With MAS XR 20-60 mg/day, mean changes in DBP (1.3 +/- 9.2 mm Hg; P=.042), SBP (2.3 +/- 12.5 mm Hg; P=.006), and pulse (2.1 +/- 13.4 bpm; P=. 0 19) were small and not clinically significant. A clinically insignificant increase in QTcB (corrected by Bazett's formula) interval (7.2 msec; P <.001) was observed at 24 months. No subject exhibited QTcB interval > 480 msec (QTcF [corrected by Fridericia's formula] > 454 msec). Seven subjects discontinued due to a cardiovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none. of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy. Conclusion: Cardiovascular effects of long-term MAS XR (:560 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.