Association of ADHD medications with the risk of cardiovascular diseases: a meta-analysis
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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.
KeywordsADHD medications All-cause death Meta-analysis Myocardial infarction Stroke Sudden death/arrhythmia
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.
The manuscript does not contain clinical studies or patient data.
- 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.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
- 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
- 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
- 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.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.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.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
- 27.Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8(47):15–17Google Scholar
- 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.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