Main Article Content

Jason Guertin
Jacques LeLorier
Madeleine Durand
Robert Gow
Anne Holbrook
Mitchell Levine


ADHD, methylphenidate, amphetamine, atomoxetine, reimbursement policy, cardiovascular events



ADHD medications increase clinical encounters for cardiovascular symptoms. Uncertain are the roles of differences in ADHD medications and restrictive practices by drug programs.


We conducted two nested case-control studies. The first was nested within a cohort of children de novo users of methylphenidate, amphetamines or atomoxetine and the second case-control study was nested within a subcohort of de novo amphetamine or atomoxetine users with no cardiovascular events prior to the first dispensing of either drug. The outcome for both studies was the composite of physician visits, emergency room visits or hospitalizations for cardiovascular reasons. Cases were matched on sex, age and date of entry within the cohorts, with up to 10 controls. Patients with an active dispensation of ADHD medications at the index date (and up to 90 days previously) were considered exposed. Conditional logistic regression was used t o calculate odd ratios (OR).


The full cohort comprised 38,495 patients. Among these patients, 3595 (9.3%) had no prior cardiovascular events (the subcohort). In the full cohort, an association was demonstrated with exposure to amphetamine and atomoxetine (but not methylphenidate) and the cardiovascular encounter outcomes. When the sub-cohort was analyzed the associations with amphetamine or atomoxetine were no longer evident.


Reimbursement policies need to be considered when conducting observational studies. Had the analysis been conducted without consideration of these policies the results would have incorrectly identified amphetamine and atomoxetine as important risk factors for cardiovascular encounters.

Abstract 228 | PDF Downloads 58


1. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder [corrected]: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation May 6 2008;117(18):2407 - 23.
2. Roman o E, Baillargeon RH, Tremblay RE. Prevalence of Hyperactivity - Impulsivity and Inattention Among Canadian Children: Findings from the First Data Collection Cycle (1994 - 1995) of the National Longitudinal Survey of Children and Youth. Hull: Human Resources Development Canada;2002.
3. Zuv ekas SH, Vitiello B. Stimulant medication use in children: A 12 - year p perspective. Am J Psychiatry 2012;169:160 - 6.
4. Centers for Disease Control and Prevention. Increasing Prevalence of Parent-Reported Attention-Deficit/Hyperactivity Disorder Among Children - United States, 2003 and 2007. MMWR Morb Mortal Wkly Rep 2010;59:1439 - 43.
5. Wilens TE, Biederman J, Lerner M, Concerta Study G. 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 Feb 2004;24(1):36 - 41.
6. Findling RL, Biederman J, Wilens TE, et al. Short - and long - term cardiovascular effects of mixed amphetamine salts extended release in children. The Journal of Pediatrics. Sep 2005;147(3):348 - 54.
7. Kratochvil CJ, Wilens TE, Greenhill LL, et al. Effects of long - term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry Aug 2006;45(8):919 - 27.
8. Wilens TE, Hammerness PG, Biederman J, et al. Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. The Journal of Clinical Psychiatry Feb 2005;66(2):253 - 9.
9. Hammerness PG, Surman CB, Chilton A. Adult attention-deficit/hyperactivity disorder treatment and cardiovascular implications. Current Psychiatry Reports Oct 2011;13(5):357 - 63.
10. Stiefel G, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention - deficit hyperactivity disorder. Drug Saf Oct 1 2010;33(10):821 - 42.
11. Nissen SE. ADHD drugs and cardiovascular risk. N Engl J Med Apr 6 2006;354(14):1445 - 8.
12. Winterstein AG, Gerhard T, Shuster J, Johnson M, Zito JM, Saidi A. Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics Dec 2007;120(6):e1494 - 501.
13. Gould MS, Walsh BT, Munfakh JL, et al. Sudden death and use of stimulant medications in yout hs. The American Journal of Psychiatry Sep 2009;166(9):992 - 1001.
14. Winterstein AG, Gerhard T, Kubilis P, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ 2012;345:e4627.
15. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 2011;365:1896 - 904.
16. McCarthy S, Cranswick N, Potts L, Taylor E, Wong IC. Mortality associated with attention - deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children, adolescents and young adults using the general practice research database. Drug Saf 2009;32(11):1089 - 96.
17. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics Jun 2011;127(6):1102 - 10.
18. Bilan démographique du Québec : Institut de la statistique du Québec; December 2010.
19. Blais C, Lambert L, Hamel D, et al. Évaluation des soins et surveillance des maladies cardiovascul aires: Pouvons - nous faire confiance aux données médico - administratives hospitalières ? Montreal: Institut national d'excellence en santé et en services sociaux (INESSS);2012.
20. Lambert L, Blais C, Hamel D, et al. Evaluation of care and surveillance of cardiovascular disease: Can we trust medico - administrative hospital data? Cdn J Cardiology 2012;28(2):162 - 8.
21. Tamblyn R, Lavoie G, Petrella L, Monette J. The use of prescription claims databases in pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims database in Quebec. J Clin Epidemiol Aug 1995;48(8):999 - 1009.
22. Tamblyn R, Reid T, Mayo N, McLeod P, Churchill - Smith M. Using medical services claims to assess injuries in the elderly: sensitivity of diagnostic and procedure codes for injury ascertainment. J Clin Epidemiol Feb 2000;53(2):183 - 94.
23. Liste des médicaments. 2012; https:// mun /PDF/Liste_Med/Liste_Med/liste_med_201 2_11_15_fr.pdf . Accessed November 20 th 2012.
24. Morrow RL, Garland EJ, Wright JM, Maclure M, Taylor S, Dormuth CR. Influence of relative age on diagnosis and treatment of attention-deficit/hyperactivity disorder in child ren. CMAJ 2012 Apr 17;184(7):755 - 62 .
25. Ray WA. Evaluating medication effects outside of clinical trials: new-user designs. American Journal of Epidemiology Nov 1 2003;158(9):915 - 20.
26. Schneeweiss S, Patrick AR, Sturmer T, et al. Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results. Medical care Oct 2007;45(10 Supl 2): S131 - 42.

Most read articles by the same author(s)

1 2 > >>