Cardiovascular Effects of Medications for the Treatment of Attention-Deficit Hyperactivity Disorder
The Children's Hospital of Philadelphia, Science Center, Philadelphia, Pennsylvania 19104, USA.Paediatric Drugs (Impact Factor: 1.98). 06/2010; 12(3):165-75. DOI: 10.2165/11532570-000000000-00000
The effective medications currently marketed for attention-deficit hyperactivity disorder (ADHD) have central and peripheral catecholaminergic effects that have been shown to result in statistically significant increases in heart rate and blood pressure. The impact of these medications on serious cardiovascular events in healthy children is unknown, but serious cardiovascular events related to ADHD medications are considered rare. However, children with cardiac pathology may be at greater risk given that increased sympathetic tone has been reported as a causal factor in generating ventricular arrhythmias in adults with coronary artery disease, and physical exercise has been consistently reported as a trigger for increased risk of sudden cardiac death in athletes with underlying cardiovascular disease. ADHD has high co-morbidity with anxiety and depression. These conditions in adults have been reported to have their own cardiovascular risks that may be compounded by interactions resulting from combined pharmacotherapeutic treatments; this interaction has not been evaluated in children. High rates of ADHD reported in subjects with cardiac pathology, as well as in patients with genetic disorders associated with cardiovascular pathology, also suggest that the prevalence of cardiac pathology in ADHD subjects may be greater than that in the general population. Currently, the US FDA and Health Canada require warnings on prescription labeling information for ADHD medications, suggesting that these medications should not generally be used in children or adults with 'known' serious cardiac pathology. Family history, medical history, and physical examination have very low sensitivity for identifying serious cardiac pathology, but this can be markedly enhanced in many instances with the use of electrocardiography, which has high specificity and sensitivity. Identifying and managing underlying cardiovascular pathology may not eliminate the risk of serious cardiovascular events but may increase the safety of using medication frequently required for effective management of ADHD. When the very common and serious consequences from untreated ADHD are also considered in the assessment of risks and benefits, even in the presence of cardiac pathology, it seems that the prescribing of ADHD medications in children should remain unchanged.
- Journal of Child and Adolescent Psychopharmacology 01/1995; 5(4):301-304. DOI:10.1089/cap.1995.5.301 · 2.93 Impact Factor
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ABSTRACT: To evaluate the safety profile, based on cardiovascular measurements, of lisdexamfetamine dimesylate (LDX) in children with and without prior exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD). This single-blind, modified laboratory school study used open-label dose optimization of children aged 6 to 12 years. Lisdexamfetamine dimesylate, initiated at 30 mg, was dose titrated in 20-mg weekly increments to a possible 70 mg over 4 to 5 weeks. Safety outcomes presented in this study were assessed using vital signs (blood pressure and pulse) and electrocardiograms, conducted at baseline and following LDX treatment. Analyses were performed across all subjects, as well as post hoc based on prior treatment status. In addition, hematologic and blood biochemistry analyses were conducted at baseline but not following treatment. Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n = 14 prior stimulant exposure; n = 13 stimulant naïve). In total, 2 subjects in the stimulant-naïve group experienced changes from baseline vital sign measurements outside the normal range: 1 with tachycardia and 1 with blood pressure ≥ 95th percentile of the normal age range. One other subject in the stimulant-naïve group experienced prolonged QTc in response to LDX, which resolved at follow-up. Pretreatment laboratory work revealed no differences on any parameters when reviewed by exposure subgroup. While LDX reduced the core symptoms of ADHD to a similar degree in treatment-naïve and previously treated groups of children with ADHD, more cardiovascular effects were measured in stimulant-naïve children than in children who had previously been exposed to stimulant treatment. Future controlled studies with larger samples should address the impact of prior stimulant exposure on other ADHD treatments.Postgraduate Medicine 09/2010; 122(5):27-34. DOI:10.3810/pgm.2010.09.2198 · 1.70 Impact Factor
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ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) is a very common condition in children and often extends into the adult years. Drugs such as methylphenidate, amphetamines and atomoxetine are frequently prescribed as part of management. The use of these drugs has been increasing and significant clinical benefit is achieved but safety has been questioned. In this review, the cardiovascular safety of these drugs is examined with regard to effects on blood pressure (BP), heart rate (HR), ECG parameters and the risk of sudden death. Methylphenidate appears to cause minor increases in BP and HR. There are no strong data to suggest that methylphenidate increases the corrected QT interval (QTc). Amphetamines appear to cause minor increases in HR and BP over the long term. There is growing evidence to suggest that amphetamines do not cause statistically or clinically significant increases in QTc. Sudden death remains an extremely rare event and there is no clear evidence to attribute this to methylphenidate. Some data even suggest that the risk of sudden death in treated children may be less common than in the background population. Limited data suggest that atomoxetine may increase BP and HR in the short term; in the long term it appears to increase BP. The effects of atomoxetine on QTc remain uncertain. Use of this drug does not appear to be associated with sudden death. Because the current evidence is based on research that has not been specifically designed to investigate the cardiovascular effects of these drugs it is difficult to draw firm conclusions, and further work is required specifically to address these questions.Drug Safety 10/2010; 33(10):821-42. DOI:10.2165/11536380-000000000-00000 · 2.82 Impact Factor
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