Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD.
ABSTRACT 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.
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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.PEDIATRICS 10/2006; 118(3):1215-9. DOI:10.1542/peds.2006-0942 · 5.30 Impact Factor
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ABSTRACT: To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity. Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed. clinicaltrials.gov Identifier: NCT00334880.The Journal of Clinical Psychiatry 12/2009; 70(12):1652-61. DOI:10.4088/JCP.09m05335pur · 5.14 Impact Factor