Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD
Duke University, Durham, North Carolina, United States CNS spectrums
(Impact Factor: 2.71).
12/2005; 10(12 Suppl 20):35-43.
To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.
223 otherwise healthy adults (>or=18 years of age) with ADHD combined subtype were exposed to <or=24 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.
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=.019) 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.
Cardiovascular effects of long-term MAS XR (<or=60 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.
Available from: ncbi.nlm.nih.gov
[Show abstract] [Hide abstract]
ABSTRACT: Assess the long-term safety and effectiveness of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype.
A 24-month, open-label extension of a 4-week, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-escalation study of MAS XR in adults (>or=18 years of age) with ADHD. The 223 enrolled subjects started treatment at 20 mg/day for 1 week, with subsequent titration up to 60 mg/day for optimal therapeutic effects. At monthly visits, efficacy was assessed based on the ADHD Rating Scale IV (ADHD-RS-IV). Safety assessments included spontaneously reported adverse events, laboratory assessments, and monitoring of vital signs.
ADHD symptoms significantly improved for all subjects as measured by change from baseline in mean ADHD-RS-IV total scores (-7.2+/-13.04 unit points; P<.001); this was sustained for up to 24 months. The most common treatment-related adverse events were dry mouth (43% of subjects reporting at least one occurrence), infection (33%), insomnia (32%), anorexia/decreased appetite (32%), headache (30%), and nervousness (26%). Most adverse events were mild to moderate in intensity.
Treatment with MAS XR 20-60 mg/day for adult ADHD was generally well tolerated and was associated with sustained symptomatic improvement for up to 24 months.
Available from: pediatrics.aappublications.org
[Show abstract] [Hide abstract]
ABSTRACT: Recently, a US Food and Drug Administration advisory committee raised concerns about cardiovascular risks and sudden death in children and adolescents with attention-deficit/hyperactivity disorder who are receiving stimulants.
We comment on the risk of sudden death in children/adolescents taking stimulants compared with population rates, biological plausibility, and known cardiovascular effects of stimulants to determine specific risk.
There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign.
There does not seem to be compelling findings of a medication-specific risk necessitating changes in our stimulant treatment of children and adolescents with attention-deficit/hyperactivity disorder. The use of existing guidelines on the use of stimulants (and psychotropic agents) may identify children, adolescents, and adults who are vulnerable to sudden death.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.