title: Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder.
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.
authors.affiliation: St Mary's Hospital, London, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Stiefel
authors.forename: Frank M C
authors.initials: FM
authors.lastname: Besag
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000662:Amphetamines / Q000009:adverse effects* / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008774:Methylphenidate / Q000009:adverse effects* / Q000627:therapeutic use; D011437:Propylamines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000662:Amphetamines; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride
references.citation: J Am Acad Child Adolesc Psychiatry. 2005 Jun;44(6):510
references.pmid: 15908831
references.citation: Clin Ther. 2007 Mar;29(3):450-63
references.pmid: 17577466
references.citation: J Am Acad Child Adolesc Psychiatry. 2006 Aug;45(8):919-927
references.pmid: 16865034
references.citation: Clin Toxicol (Phila). 2006;44(3):243-7
references.pmid: 16749540
references.citation: J Child Adolesc Psychopharmacol. 2001 Fall;11(3):251-65
references.pmid: 11642475
references.citation: Arch Pediatr Adolesc Med. 2006 Jan;160(1):82-90
references.pmid: 16389216
references.citation: Pediatrics. 2002 Mar;109(3):E39
references.pmid: 11875167
references.citation: Pediatrics. 2006 Sep;118(3):1215-9
references.pmid: 16951018
references.citation: J Child Adolesc Psychopharmacol. 2006 Jun;16(3):351-6
references.pmid: 16768642
references.citation: Arch Dis Child. 2006 Dec;91(12):1023-4
references.pmid: 17119076
references.citation: N Engl J Med. 1986 Dec 4;315(23):1485
references.pmid: 3785299
references.citation: J Clin Psychiatry. 2003 Oct;64(10):1163-9
references.pmid: 14658963
references.citation: Pediatrics. 2002 Aug;110(2 Pt 1):258-66
references.pmid: 12165576
references.citation: N Engl J Med. 2006 Apr 6;354(14):1445-8
references.pmid: 16549404
references.citation: Am J Psychiatry. 2009 Sep;166(9):992-1001
references.pmid: 19528194
references.citation: Pediatrics. 2008 Aug;122(2):451-3
references.pmid: 18676566
references.citation: Pediatrics. 2001 Oct;108(4):883-92
references.pmid: 11581440
references.citation: N Engl J Med. 2006 May 25;354(21):2296-8; author reply 2296-8
references.pmid: 16729375
references.citation: J Pediatr. 2006 Jul;149(1):112-9
references.pmid: 16860138
references.citation: Arch Gen Psychiatry. 1999 Apr;56(4):330-6
references.pmid: 10197827
references.citation: Am J Psychiatry. 2004 Apr;161(4):757
references.pmid: 15056530
references.citation: Int Clin Psychopharmacol. 1988 Apr;3(2):167-81
references.pmid: 3294285
references.citation: Pediatr Nephrol. 2006 Jan;21(1):92-5
references.pmid: 16254730
references.citation: Drug Saf. 2003;26(10):729-40
references.pmid: 12862507
references.citation: Clin Psychol Rev. 2002 Nov;22(8):1107-31
references.pmid: 12436807
references.citation: Neurology. 2005 Dec 27;65(12):1941-9
references.pmid: 16380617
references.citation: J Dev Behav Pediatr. 2008 Aug;29(4):335
references.pmid: 18698199
references.citation: J Am Acad Child Adolesc Psychiatry. 2005 Oct;44(10):1015-23
references.pmid: 16175106
references.citation: J Am Acad Child Adolesc Psychiatry. 2003 Oct;42(10):1203-11
references.pmid: 14560170
references.citation: Pediatrics. 2007 Jan;119(1):154-5
references.pmid: 17200281
references.citation: J Pediatr. 2005 Sep;147(3):348-54
references.pmid: 16182674
references.citation: Pediatrics. 1987 Jan;79(1):1-25
references.pmid: 3797155
references.citation: J Clin Pharmacol. 2005 Jul;45(7):851-5
references.pmid: 15951476
references.citation: CNS Drugs. 2008;22(3):213-37
references.pmid: 18278977
references.citation: Drug Saf. 2009;32(11):1089-96
references.pmid: 19810780
references.citation: Circulation. 2008 May 6;117(18):2407-23
references.pmid: 18427125
references.citation: J Am Acad Child Adolesc Psychiatry. 2007 Feb;46(2):242-51
references.pmid: 17242628
references.citation: J Child Adolesc Psychopharmacol. 1992 Winter;2(4):279-90
references.pmid: 19630610
references.citation: Eur Child Adolesc Psychiatry. 2006 Dec;15(8):450-9
references.pmid: 16791541
references.citation: J Am Acad Child Adolesc Psychiatry. 2001 May;40(5):525-9
references.pmid: 11349696
references.citation: Hypertension. 2007 Jul;50(1):47-53
references.pmid: 17515448
references.citation: J Child Adolesc Psychopharmacol. 2005 Aug;15(4):637-54
references.pmid: 16190795
references.citation: Adv Ther. 2007 Jan-Feb;24(1):182-8
references.pmid: 17526476
references.citation: Biol Psychiatry. 2007 Mar 1;61(5):706-12
references.pmid: 16899230
references.citation: J Am Acad Child Adolesc Psychiatry. 2002 Jul;41(7):776-84
references.pmid: 12108801
references.citation: Eur Heart J. 2001 Apr;22(8):702-11
references.pmid: 11286528
references.citation: CNS Spectr. 2008 Jul;13(7):614-20
references.pmid: 18622366
references.citation: J Child Adolesc Psychopharmacol. 2006 Aug;16(4):441-55
references.pmid: 16958569
references.citation: Drug Saf. 2009;32(11):1097-100
references.pmid: 19810781
references.citation: Child Adolesc Psychiatry Ment Health. 2007 Sep 28;1(1):11
references.pmid: 17903242
references.citation: J Clin Psychiatry. 2002 Dec;63(12):1140-7
references.pmid: 12523874
references.citation: J Clin Psychopharmacol. 2004 Feb;24(1):36-41
references.pmid: 14709945
references.citation: J Child Adolesc Psychopharmacol. 2007 Feb;17(1):63-73
references.pmid: 17343554
references.citation: Clin Ther. 2006 Feb;28(2):266-79
references.pmid: 16678648
references.citation: Pediatrics. 2003 Nov;112(5):e404
references.pmid: 14595084
references.citation: J Am Acad Child Adolesc Psychiatry. 2009 Feb;48(2):176-85
references.pmid: 20040824
references.citation: J Am Acad Child Adolesc Psychiatry. 2007 Nov;46(11):1445-53
references.pmid: 18049294
references.citation: Pediatrics. 2001 Nov;108(5):E83
references.pmid: 11694667