Pediatric Drugs

, Volume 12, Issue 3, pp 165–175 | Cite as

Cardiovascular Effects of Medications for the Treatment of Attention-Deficit Hyperactivity Disorder

What is Known and How Should it Influence Prescribing in Children?
Leading Article

Abstract

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.

References

  1. 1.
    Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007 Jun; 164(6): 942–8PubMedGoogle Scholar
  2. 2.
    Barkley RA, Fischer M, Smallish L, et al. Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry 2006 Feb; 45(2): 192–202PubMedGoogle Scholar
  3. 3.
    Kessler RC, Adler L, Ames M, et al. The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers. J Occup Environ Med 2005 Jun; 47(6): 565–72PubMedGoogle Scholar
  4. 4.
    A 14-month randomized clinical trial of treatment strategies for ADHD. The MTA Cooperative Group Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry 1999; 56: 1073–86Google Scholar
  5. 5.
    Rapport MD, Moffitt C. Attention deficit/hyperactivity disorder and methylphenidate: a review of height/weight, cardiovascular, and somatic complaint side effects. Clin Psychol Rev 2002 Nov; 22(8): 1107–31PubMedGoogle Scholar
  6. 6.
    Findling RL, Short EJ, Manos MJ. Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2001 Dec; 40(12): 1441–7PubMedGoogle Scholar
  7. 7.
    Kooij JJ, Burger H, Boonstra AM, et al. Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder: a randomized placebo-controlled double-blind cross-over trial. Psychol Med 2004 Aug; 34(6): 973–82PubMedGoogle Scholar
  8. 8.
    Swanson JM, Wigal SB, Wigal T, et al. A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyperactivity disorder in the laboratory school (the Comacs Study). Pediatrics 2004 Mar; 113 (3 Pt 1): e206–16PubMedGoogle Scholar
  9. 9.
    Findling RL, Biederman J, Wilens TE, et al. Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children. J Pediatr 2005 Sep; 147(3): 348–54PubMedGoogle Scholar
  10. 10.
    Wilens TE, Spencer TJ, Biederman J. Short- and long-term cardiovascular effects of mixed amphetamine salts extended-release in adolescents with ADHD. CNS Spectr 2005 Oct; 10 (10 Suppl. 15): 22–30PubMedGoogle Scholar
  11. 11.
    Connor DF, Spencer TJ. Short-term cardiovascular effects of mixed amphetamine salts extended release in children and adolescents with oppositional defiant disorder. CNS Spectr 2005 Oct; 10 (10 Suppl. 15): 31–8PubMedGoogle Scholar
  12. 12.
    Wilens TE, Biederman J, Lerner M. Effects of once-daily osmotic-release methylphenidate on blood pressure and heart rate in children with attention-deficit/hyperactivity disorder: results from a one-year follow-up study. J Clin Psychopharmacol 2004 Feb; 24(1): 36–41PubMedGoogle Scholar
  13. 13.
    Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr 2005 Dec; 10 (12 Suppl. 20): 35–43PubMedGoogle Scholar
  14. 14.
    Donner R, Michaels MA, Ambrosini PJ. Cardiovascular effects of mixed amphetamine salts extended release in the treatment of school-aged children with attention-deficit/hyperactivity disorder. Biol Psychiatry 2007 Mar 1; 61(5): 706–12PubMedGoogle Scholar
  15. 15.
    Wong DT, Threlkeld PG, Best KL, et al. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther 1982 Jul; 222(1): 61–5PubMedGoogle Scholar
  16. 16.
    Bolden-Watson C, Richelson E. Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 1993; 52(12): 1023–9PubMedGoogle Scholar
  17. 17.
    Zerbe RL, Rowe H, Enas GG, et al. Clinical pharmacology of tomoxetine, a potential antidepressant. J Pharmacol Exp Ther 1985 Jan; 232(1): 139–43PubMedGoogle Scholar
  18. 18.
    Michelson D, Adler L, Spencer T, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry 2003 Jan 15; 53(2): 112–20PubMedGoogle Scholar
  19. 19.
    Wernicke JF, Faries D, Girod D, et al. Cardiovascular effects of atomoxetine in children, adolescents, and adults. Drug Saf 2003; 26(10): 729–40PubMedGoogle Scholar
  20. 20.
    Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 2002 Jul; 41(7): 776–84PubMedGoogle Scholar
  21. 21.
    Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 2002 Nov; 159(11): 1896–901PubMedGoogle Scholar
  22. 22.
    Michelson D, Faries D, Wernicke J, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001 Nov; 108(5): E83PubMedGoogle Scholar
  23. 23.
    Joyce PR, Nicholls MG, Donald RA. Methylphenidate increases heart rate, blood pressure and plasma epinephrine in normal subjects. Life Sci 1984 Apr 30; 34(18): 1707–11PubMedGoogle Scholar
  24. 24.
    Samuels JA, Franco K, Wan F, et al. Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, crossover trial. Pediatr Nephrol 2006 Jan; 21(1): 92–5PubMedGoogle Scholar
  25. 25.
    Stowe CD, Gardner SF, Gist CC, et al. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Ann Pharmacother 2002 Jul–Aug; 36(7–8): 1142–9PubMedGoogle Scholar
  26. 26.
    Volkow ND, Wang GJ, Fowler JS, et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology (Berl) 2003 Mar; 166(3): 264–70Google Scholar
  27. 27.
    Pruvot E, Thonet G, Vesin JM, et al. Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter-defibrillators in patients with coronary artery disease. Circulation 2000 May 23; 101(20): 2398–404PubMedGoogle Scholar
  28. 28.
    Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990 Aug; 82 (2 Suppl.): I103–13PubMedGoogle Scholar
  29. 29.
    Maron BJ. Sudden death in young athletes. N Engl J Med 2003 Sep 11; 349(11): 1064–75PubMedGoogle Scholar
  30. 30.
    Brum G, Osterrieder W, Trautwein W. Beta-adrenergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pflugers Arch 1984 Jun; 401(2): 111–8PubMedGoogle Scholar
  31. 31.
    Janiak R, Lewartowski B. Early after-depolarisations induced by nor-adrenaline may be initiated by calcium released from sarcoplasmic reticulum. Mol Cell Biochem 1996 Oct–Nov; 163–164: 125–30PubMedGoogle Scholar
  32. 32.
    Antzelevitch C, Oliva A. Amplification of spatial dispersion of repolarization underlies sudden cardiac death associated with catecholaminergic polymorphic VT, long QT, short QT and Brugada syndromes. J Intern Med 2006 Jan; 259(1): 48–58PubMedGoogle Scholar
  33. 33.
    Ishiguro Y, Morgan JP. Biphasic inotropic effects of methamphetamine and methylphenidate on ferret papillary muscles. J Cardiovasc Pharmacol 1997 Dec; 30(6): 744–9PubMedGoogle Scholar
  34. 34.
    Jensen PS, Hinshaw SP, Kraemer HC, et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry 2001 Feb; 40(2): 147–58PubMedGoogle Scholar
  35. 35.
    Elia J, Ambrosini P, Berrettini W. ADHD characteristics: I. Concurrent comorbidity patterns in children and adolescents. Child Adolesc Psychiatry Ment Health 2008; 2(1): 2–15Google Scholar
  36. 36.
    Kawachi I, Sparrow D, Vokonas PS, et al. Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study. Circulation 1994 Nov; 90(5): 2225–9PubMedGoogle Scholar
  37. 37.
    Yeragani VK, Sobolewski E, Igel G, et al. Decreased heart-period variability in patients with panic disorder: a study of Holter ECG records. Psychiatry Res 1998 Mar 20; 78(1–2): 89–99PubMedGoogle Scholar
  38. 38.
    Yeragani VK, Kumar HV. Heart period and QT variability, hostility, and type-A behavior in normal controls and patients with panic disorder. J Psychosom Res 2000 Dec; 49(6): 401–7PubMedGoogle Scholar
  39. 39.
    Yeragani VK, Pohl R, Jampala VC, et al. Increased QT variability in patients with panic disorder and depression. Psychiatry Res 2000 Apr 10; 93(3): 225–35PubMedGoogle Scholar
  40. 40.
    Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998 Jul; 55(7): 580–92PubMedGoogle Scholar
  41. 41.
    Watkins LL, Blumenthal JA, Davidson JR, et al. Phobic anxiety, depression, and risk of ventricular arrhythmias in patients with coronary heart disease. Psychosom Med 2006 Sep–Oct; 68(5): 651–6PubMedGoogle Scholar
  42. 42.
    Jensen PS, Martin D, Cantwell DP. Comorbidity in ADHD: implications for research, practice, and DSM-V. J Am Acad Child Adolesc Psychiatry 1997 Aug; 36(8): 1065–79PubMedGoogle Scholar
  43. 43.
    Bigger Jr JT, Fleiss JL, Rolnitzky LM, et al. Stability over time of heart period variability in patients with previous myocardial infarction and ventricular arrhythmias. The CAPS and ESVEM investigators. Am J Cardiol 1992 Mar 15; 69(8): 718–23PubMedGoogle Scholar
  44. 44.
    Molgaard H, Sorensen KE, Bjerregaard P. Attenuated 24-h heart rate variability in apparently healthy subjects, subsequently suffering sudden cardiac death. Clin Auton Res 1991 Sep; 1(3): 233–7PubMedGoogle Scholar
  45. 45.
    Friedman BH. An autonomic flexibility-neurovisceral integration model of anxiety and cardiac vagal tone. Biol Psychol 2007 Feb; 74(2): 185–99PubMedGoogle Scholar
  46. 46.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association, 2000Google Scholar
  47. 47.
    Friedman BH, Thayer JF. Anxiety and autonomic flexibility: a cardiovascular approach. Biol Psychol 1998 Mar; 47(3): 243–63PubMedGoogle Scholar
  48. 48.
    Gorman JM, Sloan RP. Heart rate variability in depressive and anxiety disorders. Am Heart J 2000 Oct; 140 (4 Suppl.): 77–83PubMedGoogle Scholar
  49. 49.
    Patrick KS, Kilts CD, Breese GR. Synthesis and pharmacology of hydroxylated metabolites of methylphenidate. J Med Chem 1981 Oct; 24(10): 1237–40PubMedGoogle Scholar
  50. 50.
    DeVane CL, Markowitz JS, Carson SW, et al. Single-dose pharmacokinetics of methylphenidate in CYP2D6 extensive and poor metabolizers. J Clin Psychopharmacol 2000 Jun; 20(3): 347–9PubMedGoogle Scholar
  51. 51.
    Dring LG, Smith RL, Williams RT. The metabolic fate of amphetamine in man and other species. Biochem J 1970 Feb; 116(3): 425–35PubMedGoogle Scholar
  52. 52.
    Tomkins DM, Otton SV, Joharchi N, et al. Effect of CYP2D1 inhibition on the behavioural effects of d-amphetamine. Behav Pharmacol 1997 Jun; 8(2–3): 223–35PubMedGoogle Scholar
  53. 53.
    Swanson J, Flockhart D, Udrea D, et al. Clonidine in the treatment of ADHD: questions about safety and efficacy. J Child Adolesc Psychopharmacol 1995; 5: 301–4Google Scholar
  54. 54.
    Cantwell DP, Swanson J, Connor DF. Case study: adverse response to clonidine. J Am Acad Child Adolesc Psychiatry 1997 Apr; 36(4): 539–44PubMedGoogle Scholar
  55. 55.
    Sallee FR, DeVane CL, Ferrell RE. Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency. J Child Adolesc Psychopharmacol 2000 Spring; 10(1): 27–34PubMedGoogle Scholar
  56. 56.
    Gracious BL. Atrioventricular nodal re-entrant tachycardia associated with stimulant treatment. J Child Adolesc Psychopharmacol 1999; 9(2): 125–8PubMedGoogle Scholar
  57. 57.
    DeVane CL. Metabolism and pharmacokinetics of selective serotonin reup-take inhibitors. Cell Mol Neurobiol 1999 Aug; 19(4): 443–66PubMedGoogle Scholar
  58. 58.
    Sills TL, Greenshaw AJ, Baker GB, et al. Acute fluoxetine treatment potentiates amphetamine hyperactivity and amphetamine-induced nucleus accumbens dopamine release: possible pharmacokinetic interaction. Psychopharmacology 1999 Feb; 141(4): 421–7PubMedGoogle Scholar
  59. 59.
    Sills TL, Greenshaw AJ, Baker GB, et al. Subchronic fluoxetine treatment induces a transient potentiation of amphetamine-induced hyperlocomotion: possible pharmacokinetic interaction. Behav Pharmacol 2000 Apr; 11(2): 109–16PubMedGoogle Scholar
  60. 60.
    Perruchoud C, Chollet-Rivier M. Cardiac arrest during induction of anaesthesia in a child on long-term amphetamine therapy. Br J Anaesth 2008 Mar; 100(3): 421–2PubMedGoogle Scholar
  61. 61.
    Zhu HJ, Patrick KS, Yuan HJ, et al. Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet 2008 Jun; 82(6): 1241–8PubMedGoogle Scholar
  62. 62.
    Shillingford AJ, Wernovsky G. Academic performance and behavioral difficulties after neonatal and infant heart surgery. Pediatr Clin North Am 2004 Dec; 51(6): 1625–39, ixPubMedGoogle Scholar
  63. 63.
    Kirshbom PM, Flynn TB, Clancy RR, et al. Late neurodevelopmental outcome after repair of total anomalous pulmonary venous connection. J Thorac Cardiovasc Surg 2005 May; 129(5): 1091–7PubMedGoogle Scholar
  64. 64.
    Mahle WT, Clancy RR, Moss EM, et al. Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome. Pediatrics 2000 May; 105(5): 1082–9PubMedGoogle Scholar
  65. 65.
    Gaynor JW, Nord AS, Wernovsky G, et al. Apolipoportein E genotype modifies the risk of behavior problems after infant cardiac surgery. Pediatrics 2009; 124: 241–50PubMedGoogle Scholar
  66. 66.
    Hofman KJ, Bernhardt BA, Pyeritz RE. Marfan syndrome: neuropsychological aspects. Am J Med Genet 1988 Oct; 31(2): 331–8PubMedGoogle Scholar
  67. 67.
    Gothelf D, Gruber R, Presburger G, et al. Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study. J Clin Psychiatry 2003 Oct; 64(10): 1163–9PubMedGoogle Scholar
  68. 68.
    Russell HF, Wallis D, Mazzocco MM, et al. Increased prevalence of ADHD in Turner syndrome with no evidence of imprinting effects. J Pediatr Psychol 2006 Oct; 31(9): 945–55PubMedGoogle Scholar
  69. 69.
    Stuart AG, Williams A. Marfan’s syndrome and the heart. Arch Dis Child 2007 Apr; 92(4): 351–6PubMedGoogle Scholar
  70. 70.
    Radford DJ, Izukawa T. Atrial fibrillation in children. Pediatrics 1977 Feb; 59(2): 250–6PubMedGoogle Scholar
  71. 71.
    Johnson CD. The Wolff-Parkinson-White syndrome associated with Marfan’s syndrome. Bol Asoc Med P R 1989 Sep; 81(9): 361–4PubMedGoogle Scholar
  72. 72.
    Yetman AT, Bornemeier RA, McCrindle BW. Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death? J Am Coll Cardiol 2003 Jan 15; 41(2): 329–32PubMedGoogle Scholar
  73. 73.
    Chen S, Fagan LF, Nouri S, et al. Ventricular dysrhythmias in children with Marfan’s syndrome. Am J Dis Child 1985 Mar; 139(3): 273–6PubMedGoogle Scholar
  74. 74.
    Savolainen A, Kupari M, Toivonen L, et al. Abnormal ambulatory electrocardiographic findings in patients with the Marfan syndrome. J Intern Med 1997 Mar; 241(3): 221–6PubMedGoogle Scholar
  75. 75.
    Dell’Anna ME, Luthman J, Lindqvist E, et al. Development of monoamine systems after neonatal anoxia in rats. Brain Res Bull 1993; 32(2): 159–70PubMedGoogle Scholar
  76. 76.
    Dell’Anna ME, Calzolari S, Molinari M, et al. Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats. Behav Brain Res 1991 Nov 26; 45(2): 125–34PubMedGoogle Scholar
  77. 77.
    Lou HC. Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatr 1996 Nov; 85(11): 1266–71PubMedGoogle Scholar
  78. 78.
    Toft PB. Prenatal and perinatal striatal injury: a hypothetical cause of attention-deficit-hyperactivity disorder? Pediatr Neurol 1999 Sep; 21(3): 602–10PubMedGoogle Scholar
  79. 79.
    Winterstein AG, Gerhard T, Shuster J, et al. Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 2007 Dec; 120(6): e1494–501PubMedGoogle Scholar
  80. 80.
    Winterstein AG, Gerhard T, Shuster J, et al. Cardiac safety of methylpheni-date versus amphetamine salts in the treatment of ADHD. Pediatrics 2009; 124(1): e75–80PubMedGoogle Scholar
  81. 81.
    Wooltorton E. Medications for attention deficit hyperactivity disorder: cardiovascular concerns. CMAJ 2006 Jul 4; 175(1): 29–30PubMedGoogle Scholar
  82. 82.
    Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007 Jul; 46(7): 894–921PubMedGoogle Scholar
  83. 83.
    Perrin JM, Friedman RA, Knilans TK. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics 2008 Aug; 122(2): 451–3PubMedGoogle Scholar
  84. 84.
    Warren AE, Hamilton RM, Belanger SA, et al. Cardiac risk assessment before the use of stimulant medications in children and youth: a joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry. Can J Cardiol 2009; 25: 625–30PubMedGoogle Scholar
  85. 85.
    Wilson MG, Basavarajaiah S, Whyte GP, et al. Efficacy of personal symptom and family history questionnaires when screening for inherited cardiac pathologies: the role of electrocardiography. Br J Sports Med 2008; 42: 207–11PubMedGoogle Scholar
  86. 86.
    Corrado D, Basso C, Schiavon M, et al. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998 Aug 6; 339(6): 364–9PubMedGoogle Scholar
  87. 87.
    Sano S, Komori S, Amano T, et al. Prevalence of ventricular preexcitation in Japanese school children. Heart 1998 Apr; 79(4): 374–8PubMedGoogle Scholar
  88. 88.
    Tanaka Y, Yoshinaga M, Anan R, et al. Usefulness and cost effectiveness of cardiovascular screening of young adolescents. Med Sci Sports Exerc 2006 Jan; 38(1): 2–6PubMedGoogle Scholar
  89. 89.
    Fuller CM, McNulty CM, Spring DA, et al. Prospective screening of 5615 high school athletes for risk of sudden cardiac death. Med Sci Sports Exerc 1997 Sep; 29(9): 1131–8PubMedGoogle Scholar
  90. 90.
    Basavarajaiah S, Wilson M, Whyte G, et al. Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening. J Am Coll Cardiol 2008 Mar 11; 51(10): 1033–9PubMedGoogle Scholar
  91. 91.
    Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update. A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007 Mar 27; 115(12): 1643–55PubMedGoogle Scholar
  92. 92.
    Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002 Mar 13; 287(10): 1308–20PubMedGoogle Scholar
  93. 93.
    Maron BJ, Roberts WC, Epstein SE. Sudden death in hypertrophic cardiomyopathy: a profile of 78 patients. Circulation 1982 Jun; 65(7): 1388–94PubMedGoogle Scholar
  94. 94.
    Goldenberg I, Moss AJ, Peterson DR, et al. Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome. Circulation 2008 Apr 29; 117(17): 2184–91PubMedGoogle Scholar
  95. 95.
    Maron BJ, Shirani J, Poliac LC, et al. Sudden death in young competitive athletes: clinical, demographic, and pathological profiles. JAMA 1996 Jul 17; 276(3): 199–204PubMedGoogle Scholar
  96. 96.
    Liberthson RR. Sudden death from cardiac causes in children and young adults. N Engl J Med 1996 Apr 18; 334(16): 1039–44PubMedGoogle Scholar
  97. 97.
    Basso C, Maron BJ, Corrado D, et al. Clinical profile of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol 2000 May; 35(6): 1493–501PubMedGoogle Scholar
  98. 98.
    Davis JA, Cecchin F, Jones TK, et al. Major coronary artery anomalies in a pediatric population: incidence and clinical importance. J Am Coll Cardiol 2001 Feb; 37(2): 593–7PubMedGoogle Scholar
  99. 99.
    Fuller CM. Cost effectiveness analysis of screening of high school athletes for risk of sudden cardiac death. Med Sci Sports Exerc 2000 May; 32(5): 887–90PubMedGoogle Scholar
  100. 100.
    Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000 Jul 18; 102(3): 278–84PubMedGoogle Scholar
  101. 101.
    Pelliccia A, Culasso F, Di Paolo FM, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur Heart J 2007 Aug; 28(16): 2006–10PubMedGoogle Scholar
  102. 102.
    Mahle WT, Hebson C, Strieper MJ. Electrocardiographic screening in children with ADHD. Am Cardiol 2009; 104: 1296–9Google Scholar
  103. 103.
    Corrado D, Basso C, Pavei A, et al. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006 Oct 4; 296(13): 1593–601PubMedGoogle Scholar
  104. 104.
    Daly MW, Custer G, McLeay PD. Cardiac arrest with pulseless electrical activity associated with methylphenidate in an adolescent with a normal baseline echocardiogram. Pharmacotherapy 2008 Nov; 28(11): 1408–12PubMedGoogle Scholar
  105. 105.
    Gould MS, Walsh BT, Munfakh JL, et al. Sudden death and use of stimulant medications in youths. Am J Psychiatry 2009; 166: 992–1001PubMedGoogle Scholar
  106. 106.
    Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002 Dec 14; 360(9349): 1903–13PubMedGoogle Scholar
  107. 107.
    Faraone SV, Biederman J, Mennin D, et al. A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome. J Am Acad Child Adolesc Psychiatry 1996 Nov; 35(11): 1449–59PubMedGoogle Scholar
  108. 108.
    Foley HA, Carlton CO, Howell RJ. The relationship of attention deficit hyperactivity disorder and conduct disorder to juvenile delinquency: legal implications. Bull Am Acad Psychiatry Law 1996; 24(3): 333–45PubMedGoogle Scholar
  109. 109.
    Greenfield B, Hechtman L, Weiss G. Two subgroups of hyperactives as adults: correlations of outcome. Can J Psychiatry 1988 Aug; 33(6): 505–8PubMedGoogle Scholar
  110. 110.
    Strine TW, Lesesne CA, Okoro CA, et al. Emotional and behavioral difficulties and impairments in everyday functioning among children with a history of attention-deficit/hyperactivity disorder. Prev Chronic Dis 2006 Apr; 3(2): A52PubMedGoogle Scholar
  111. 111.
    Barkley RA, Murphy KR, Kwasnik D. Motor vehicle driving competencies and risks in teens and young adults with attention deficit hyperactivity disorder. Pediatrics 1996 Dec; 98 (6 Pt 1): 1089–95PubMedGoogle Scholar
  112. 112.
    Barkley RA, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993 Aug; 92(2): 212–8PubMedGoogle Scholar
  113. 113.
    Cox DJ, Merkel RL, Kovatchev B, et al. Effect of stimulant medication on driving performance of young adults with attention-deficit hyperactivity disorder: a preliminary double-blind placebo controlled trial. J Nerv Ment Dis 2000 Apr; 188(4): 230–4PubMedGoogle Scholar
  114. 114.
    Fischer M, Barkley RA, Smallish L, et al. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes. Accid Anal Prev 2007 Jan; 39(1): 94–105PubMedGoogle Scholar
  115. 115.
    Mannuzza S, Klein RG, Bessler A, et al. Adult outcome of hyperactive boys: educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry 1993 Jul; 50(7): 565–76PubMedGoogle Scholar
  116. 116.
    Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 1998 Apr; 155(4): 493–8PubMedGoogle Scholar
  117. 117.
    Weiss G, Hechtman L. Hyperactive children grown. 2nd ed. New York: Guilford Press, 1993Google Scholar
  118. 118.
    Barkley RA, Fischer M, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 1990 Jul; 29(4): 546–57PubMedGoogle Scholar
  119. 119.
    Biederman J, Monuteaux MC, Doyle AE, et al. Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. J Consult Clin Psychol 2004 Oct; 72(5): 757–66PubMedGoogle Scholar
  120. 120.
    Maedgen JW, Carlson CL. Social functioning and emotional regulation in the attention deficit hyperactivity disorder subtypes. J Clin Child Psychol 2000 Mar; 29(1): 30–42PubMedGoogle Scholar
  121. 121.
    Biederman J, Mick E, Faraone SV. Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Am J Psychiatry 2000 May; 157(5): 816–8PubMedGoogle Scholar
  122. 122.
    Weiss RE, Stein MA, Trommer B, et al. Attention-deficit hyperactivity disorder and thyroid function. J Pediatr 1993 Oct; 123(4): 539–45PubMedGoogle Scholar
  123. 123.
    Pomerleau OF, Downey KK, Stelson FW, et al. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse 1995; 7(3): 373–8PubMedGoogle Scholar
  124. 124.
    Biederman J, Wilens TE, Mick E, et al. Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence? Biol Psychiatry 1998 Aug 15; 44(4): 269–73PubMedGoogle Scholar
  125. 125.
    Humfleet GL, Prochaska JJ, Mengis M, et al. Preliminary evidence of the association between the history of childhood attention-deficit/hyperactivity disorder and smoking treatment failure. Nicotine Tob Res 2005 Jun; 7(3): 453–60PubMedGoogle Scholar
  126. 126.
    Lambert NM, Hartsough CS. Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil 1998 Nov–Dec; 31(6): 533–44PubMedGoogle Scholar
  127. 127.
    Milberger S, Biederman J, Faraone SV, et al. ADHD is associated with early initiation of cigarette smoking in children and adolescents. J Am Acad Child Adolesc Psychiatry 1997 Jan; 36(1): 37–44PubMedGoogle Scholar

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© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.The Children’s Hospital of PhiladelphiaPennsylvaniaUSA
  2. 2.The University of PennsylvaniaPhiladelphiaUSA

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