Advertisement

European Child & Adolescent Psychiatry

, Volume 28, Issue 10, pp 1283–1293 | Cite as

Association of ADHD medications with the risk of cardiovascular diseases: a meta-analysis

  • Hui Liu
  • Wenjing Feng
  • Dongfeng ZhangEmail author
Review

Abstract

This meta-analysis was conducted to evaluate the association between Attention deficit hyperactivity disorder (ADHD) medications and risk of sudden death/arrhythmia, stroke, myocardial infarction as well as all-cause death. We searched PubMed, Web of Science and China National Knowledge Infrastructure from 1950 to May 2018. All observational studies that the exposure of interest was ADHD medications, the outcome of interest was sudden death/arrhythmia, stroke, myocardial infarction as well as all-cause death, and the study reported relative risks (RRs) with 95% confidence intervals (95% CIs) were included. Pooled RRs were estimated by random-effects model. Subgroup analyses were conducted to examine the effects of study design, population, Country, follow-up duration, female proportion, covariates adjustment on the risk of sudden death/arrhythmia. Eight articles with ten studies (4,221,929 participants) were included in this meta-analysis about the association between ADHD medications and risk of sudden death/arrhythmia. The pooled RRs with 95% CIs of sudden death/arrhythmia for ADHD medications were 1.39 (1.06, 1.83). The result of the cohort study was 1.24 (0.84, 1.83). The pooled RRs between ADHD medications and stroke, myocardial infarction, all-cause death were 1.00 (0.74, 1.35), 0.91 (0.79, 1.05), 0.89 (0.54, 1.45), respectively. As for methylphenidate, the pooled RRs between methylphenidate and sudden death/arrhythmia, stroke, myocardial infarction, all-cause death were 1.46 (1.03, 2.07), 0.92 (0.70, 1.21), 0.97 (0.77, 1.23), 1.00 (0.49, 2.04), respectively. Based on the results of cohort studies, there was no correlation between ADHD medications and sudden death/arrhythmia, stroke, myocardial infarction and all-cause death. However, some of the confidence intervals do not exclude modest elevated risks, e.g., for sudden death/arrhythmia.

Keywords

ADHD medications All-cause death Meta-analysis Myocardial infarction Stroke Sudden death/arrhythmia 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of Interest

The authors report no financial or other relationship relevant to the subject of this article.

Ethical standards

The manuscript does not contain clinical studies or patient data.

References

  1. 1.
    Childress AC, Berry SA (2012) Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents. Drugs 72(3):309–325.  https://doi.org/10.2165/11599580-000000000-00000 CrossRefPubMedGoogle Scholar
  2. 2.
    Sharma A, Couture J (2014) A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother 48(2):209–225.  https://doi.org/10.1177/1060028013510699 CrossRefPubMedGoogle Scholar
  3. 3.
    Skounti M, Philalithis A, Galanakis E (2007) Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr 166(2):117–123.  https://doi.org/10.1007/s00431-006-0299-5 CrossRefPubMedGoogle Scholar
  4. 4.
    Modesto-Lowe V, Meyer A, Soovajian V (2012) A clinican’s guide to adult attention-deficit hyperactivity disorder. Conn Med 76(9):517–523PubMedGoogle Scholar
  5. 5.
    Advokat C (2010) What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD). Neurosci Biobehav Rev 34(8):1256–1266.  https://doi.org/10.1016/j.neubiorev.2010.03.006 CrossRefPubMedGoogle Scholar
  6. 6.
    Pliszka S (2007) Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 46(7):894–921.  https://doi.org/10.1097/chi.0b013e318054e724 CrossRefPubMedGoogle Scholar
  7. 7.
    Taylor E, Dopfner M, Sergeant J, Asherson P, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Rothenberger A, Sonuga-Barke E, Steinhausen HC, Zuddas A (2004) European clinical guidelines for hyperkinetic disorder—first upgrade. Eur Child Adolesc Psychiatry 13(Suppl 1):I7–I30.  https://doi.org/10.1007/s00787-004-1002-x CrossRefPubMedGoogle Scholar
  8. 8.
    Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, Danckaerts M, Dopfner M, Faraone SV, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke EJ, Taylor E (2006) Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur Child Adolesc Psychiatry 15(8):476–495.  https://doi.org/10.1007/s00787-006-0549-0 CrossRefPubMedGoogle Scholar
  9. 9.
    Hammerness PG, Surman CB, Chilton A (2011) Adult attention-deficit/hyperactivity disorder treatment and cardiovascular implications. Curr Psychiatry Rep 13(5):357–363.  https://doi.org/10.1007/s11920-011-0213-3 CrossRefPubMedGoogle Scholar
  10. 10.
    Faraone SV, Glatt SJ (2010) A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes. J Clin Psychiatry 71(6):754–763.  https://doi.org/10.4088/JCP.08m04902pur CrossRefPubMedGoogle Scholar
  11. 11.
    Hennissen L, Bakker MJ, Banaschewski T, Carucci S, Coghill D, Danckaerts M, Dittmann RW, Hollis C, Kovshoff H, McCarthy S, Nagy P, Sonuga-Barke E, Wong IC, Zuddas A, Rosenthal E, Buitelaar JK (2017) Cardiovascular effects of stimulant and non-stimulant medication for children and adolescents with ADHD: a systematic review and meta-analysis of trials of methylphenidate, amphetamines and atomoxetine. CNS Drugs 31(3):199–215.  https://doi.org/10.1007/s40263-017-0410-7 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mick E, McManus DD, Goldberg RJ (2013) Meta-analysis of increased heart rate and blood pressure associated with CNS stimulant treatment of ADHD in adults. Eur Neuropsychopharmacol 23(6):534–541.  https://doi.org/10.1016/j.euroneuro.2012.06.011 CrossRefPubMedGoogle Scholar
  13. 13.
    Nissen SE (2006) ADHD drugs and cardiovascular risk. N Engl J Med 354(14):1445–1448.  https://doi.org/10.1056/NEJMp068049 CrossRefPubMedGoogle Scholar
  14. 14.
    Shin JY, Roughead EE, Park BJ, Pratt NL (2016) Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. BMJ 353:i2550.  https://doi.org/10.1136/bmj.i2550 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Huang MC, Yang SY, Lin SK, Chen KY, Chen YY, Kuo CJ, Hung YN (2016) Risk of cardiovascular diseases and stroke events in methamphetamine users: a 10-year follow-up study. J Clin Psychiatry 77(10):1396–1403.  https://doi.org/10.4088/JCP.15m09872 CrossRefPubMedGoogle Scholar
  16. 16.
    Gould MSWB, Munfakh JL, Kleinman M, Duan N, Olfson M, Greenhill L, Cooper T (2009) Sudden death and use of stimulant medications in youths. Am J Psychiatry 166(9):992–1001CrossRefGoogle Scholar
  17. 17.
    Schelleman H, Bilker WB, Kimmel SE, Daniel GW, Newcomb C, Guevara JP, Cziraky MJ, Strom BL, Hennessy S (2012) Methylphenidate and risk of serious cardiovascular events in adults. Am J Psychiatry 169(2):178–185.  https://doi.org/10.1176/appi.ajp.2011.11010125 CrossRefPubMedGoogle Scholar
  18. 18.
    Schelleman H, Bilker WB, Kimmel SE, Daniel GW, Newcomb C, Guevara JP, Cziraky MJ, Strom BL, Hennessy S (2013) Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults. PLoS One 8(1):e52991.  https://doi.org/10.1371/journal.pone.0052991 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Schelleman H, Bilker WB, Strom BL, Kimmel SE, Newcomb C, Guevara JP, Daniel GW, Cziraky MJ, Hennessy S (2011) Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics 127(6):1102–1110.  https://doi.org/10.1542/peds.2010-3371 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (2011) ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA 306(24):2673–2683.  https://doi.org/10.1001/jama.2011.1830 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O’Duffy A, Connell FA, Ray WA (2011) ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 365(20):1896–1904.  https://doi.org/10.1056/NEJMoa1110212 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269CrossRefGoogle Scholar
  23. 23.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560.  https://doi.org/10.1136/bmj.327.7414.557 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Goel R, Srivathsan K, Mookadam M (2013) Supraventricular and ventricular arrhythmias. Prim Care 40(1):43–71.  https://doi.org/10.1016/j.pop.2012.11.002 CrossRefPubMedGoogle Scholar
  25. 25.
    Higgins JP, Thompson SG (2004) Controlling the risk of spurious findings from meta-regression. Stat Med 23(11):1663–1682.  https://doi.org/10.1002/sim.1752 CrossRefPubMedGoogle Scholar
  26. 26.
    Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37(5):1148–1157.  https://doi.org/10.1093/ije/dyn065 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8(47):15–17Google Scholar
  28. 28.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefGoogle Scholar
  29. 29.
    Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605.  https://doi.org/10.1007/s10654-010-9491-z CrossRefPubMedGoogle Scholar
  30. 30.
    Mazza M, D’Ascenzo F, Davico C, Biondi-Zoccai G, Frati G, Romagnoli E, Bassi B, Janiri L, Moretti C, Gaita F (2013) Drugs for attention deficit-hyperactivity disorder do not increase the mid-term risk of sudden death in children: a meta-analysis of observational studies. Int J Cardiol 168(4):4320–4321.  https://doi.org/10.1016/j.ijcard.2013.04.169 CrossRefPubMedGoogle Scholar
  31. 31.
    Volkow ND, Wang GJ, Fowler JS, Molina PE, Logan J, Gatley SJ, Gifford A, Ding YS, Wong C, Pappas NR, Zhu W, Swanson JM (2003) Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology 166(3):264–270.  https://doi.org/10.1007/s00213-002-1340-7 CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang D, Wang W, Li F (2016) Association between resting heart rate and coronary artery disease, stroke, sudden death and noncardiovascular diseases: a meta-analysis. CMAJ 188(15):E384–e392.  https://doi.org/10.1503/cmaj.160050 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Gopinathannair R, Martins JB (2008) Predicting sudden cardiac death in healthy humans: is there more to autonomic balance than we know? Heart Rhythm 5(2):306–307.  https://doi.org/10.1016/j.hrthm.2007.10.038 CrossRefPubMedGoogle Scholar
  34. 34.
    Laukkanen JA, Jennings JR, Kauhanen J, Makikallio TH, Ronkainen K, Kurl S (2012) Relation of systemic blood pressure to sudden cardiac death. Am J Cardiol 110(3):378–382.  https://doi.org/10.1016/j.amjcard.2012.03.035 CrossRefPubMedGoogle Scholar
  35. 35.
    Ghali JK, Kadakia S, Cooper RS, Liao YL (1991) Impact of left ventricular hypertrophy on ventricular arrhythmias in the absence of coronary artery disease. J Am Coll Cardiol 17(6):1277–1282CrossRefGoogle Scholar
  36. 36.
    Siegel D, Cheitlin MD, Black DM, Seeley D, Hearst N, Hulley SB (1990) Risk of ventricular arrhythmias in hypertensive men with left ventricular hypertrophy. Am J Cardiol 65(11):742–747CrossRefGoogle Scholar
  37. 37.
    Szlachcic J, Tubau JF, O’Kelly B, Ammon S, Daiss K, Massie BM (1992) What is the role of silent coronary artery disease and left ventricular hypertrophy in the genesis of ventricular arrhythmias in men with essential hypertension? J Am Coll Cardiol 19(4):803–808CrossRefGoogle Scholar
  38. 38.
    Burke AP, Farb A, Malcom GT, Liang Y, Smialek JE, Virmani R (1999) Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 281(10):921–926CrossRefGoogle Scholar
  39. 39.
    Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R (1997) Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 336(18):1276–1282.  https://doi.org/10.1056/nejm199705013361802 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Epidemiology and Health Statistics, Public Health CollegeQingdao UniversityQingdaoChina
  2. 2.Department of Geriatric Internal MedicineThe Affiliated Hospital of Qingdao UniversityQingdaoChina

Personalised recommendations