Science
Stimulant medication and heart health
What the research shows
Central nervous system stimulants such as Adderall, Ritalin, and Vyvanse are commonly used to treat ADHD and narcolepsy in children and adults. Common side effects of these drugs are increased blood pressure and heart rate. Anecdotally, many patients and doctors assume that there are negative long-term heart consequences for stimulant use, even when taken as prescribed and in approved doses. The purpose of this article is to review the available research and determine if this concern is supported by the evidence.
Disclaimers
I am not a doctor. This is not medical advice. Consult your doctor before starting any new treatment.
I acknowledge that I have a bias in favor of stimulant treatment for ADHD. I’ve listened to many ADHD experts speak on the subject and they have an overwhelming consensus view in favor of it. I made every effort to set this bias aside while researching the topic.
Hypothesis
My guess is that stimulant use would lead to a small increase in adverse cardiovascular events like heart attack and stroke, more frequently in adults, and especially in patients with preexisting heart conditions.
Methodology
I searched PubMed for the term “stimulant heart.” I considered the first 50 results, as well as the “Similar articles” for each relevant study, and each of their “Similar articles,” following the chain of related articles until no more relevant articles were found. I ignored studies that were about caffeine, MDMA, cocaine, or intentional drug abuse, or did not consider heart health. I also ignored the few studies that did not have an abstract or summary publicly available on PubMed. Personal bias was not a criteria for exclusion. I reviewed and summarized the abstract, results, or conclusion of each relevant study, with a total of 37 studies found. Skip to the bottom for a general summary.
Studies
Stimulant medication is effective “for all age groups” including adults and has “a good safety profile.”
Dopheide JA, Pliszka SR. Attention-deficit-hyperactivity disorder: an update. Pharmacotherapy. 2009 Jun;29(6):656-79. doi: 10.1592/phco.29.6.656. PMID: 19476419. Link
“Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion.”
Weibel S, Menard O, Ionita A, Boumendjel M, Cabelguen C, Kraemer C, Micoulaud-Franchi JA, Bioulac S, Perroud N, Sauvaget A, Carton L, Gachet M, Lopez R. Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults. Encephale. 2020 Feb;46(1):30-40. doi: 10.1016/j.encep.2019.06.005. Epub 2019 Oct 11. PMID: 31610922. Link
A review of 10 studies on stimulant use for ADHD in adults aged 22 to 40 found an increase in resting heart rate (+5.7 bpm; a normal resting heart rate is between 60 and 100 bpm) and systolic blood pressure (+2 mmHg; normal systolic blood pressure is 120 mmHg or less). The study did not include clinical outcomes and recommended further research.
Mick E, McManus DD, Goldberg RJ. Meta-analysis of increased heart rate and blood pressure associated with CNS stimulant treatment of ADHD in adults. Eur Neuropsychopharmacol. 2013 Jun;23(6):534-41. doi: 10.1016/j.euroneuro.2012.06.011. Epub 2012 Jul 15. PMID: 22796229; PMCID: PMC3488604. Link
This meta-analysis acknowledges concerns about “the potential for rare but serious cardiovascular adverse events” when stimulants are used to treat ADHD. It notes that both stimulants and non-stimulants, such as atomoxetine (Strattera), can increase blood pressure and heart rate. Guanfacine and clonidine (α(2)-adrenergic agonists, also non-stimulants) are known to cause small decreases in blood pressure and heart rate. But across all modes of treatment, the review finds that “The risk for serious cardiovascular adverse events, including statistically or clinically significant increases in QTc, and sudden cardiac death associated with stimulants, atomoxetine or α(2)-adrenergic agonists prescribed for ADHD is extremely low and the benefits of treating individual patients with ADHD, after an adequate assessment, outweigh the risks. However, great caution is advised when considering stimulant and non-stimulant medications for patients of any age with a diagnosis of ADHD and a personal or family history or other known risk factors for cardiovascular disease.”
Martinez-Raga J, Knecht C, Szerman N, Martinez MI. Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder. CNS Drugs. 2013 Jan;27(1):15-30. doi: 10.1007/s40263-012-0019-9. PMID: 23160939. Link
“Currently available data suggest that there is no evidence for serious adverse cardiovascular complications in children with known cardiovascular diseases including patients of congenital heart disease who are treated with stimulant medications. Despite this, if the patient does have known cardiac disease, or if the history and physical examination is suggestive of cardiac disease, it is suggested that consultation/evaluation with a pediatric cardiologist occur. It is extremely unlikely that stimulant medications would be contraindicated in almost any condition that falls under this category. However, a few specific cardiac conditions might tailor the choice of the specific ADHD medication.”
Berger S. Attention deficit hyperactivity disorder medications in children with heart disease. Curr Opin Pediatr. 2016 Oct;28(5):607-12. doi: 10.1097/MOP.0000000000000388. PMID: 27261563. Link
“Clinical diagnoses of cardiovascular events and symptoms were rare and not associated with stimulant use. The results help to allay concerns over the cardiovascular safety of stimulant treatment for attention-deficit/hyperactivity disorder in young people without known pre-existing risk factors.”
Olfson M, Huang C, Gerhard T, Winterstein AG, Crystal S, Allison PD, Marcus SC. Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):147-56. doi: 10.1016/j.jaac.2011.11.008. Epub 2011 Dec 20. PMID: 22265361; PMCID: PMC3266532. Link
“In the past two years, large retrospective, population-based cohort studies were performed. These studies did not show any evidence that methylphenidate was associated with an increase in risk of myocardial infarction, sudden cardiac death, or stroke. Treatment of children with methylphenidate is not significantly associated with an increase in the short term or mid-term risk of severe cardiac events.” The study notes, however, that there are gaps in our knowledge; there may be long-term effects on heart rate and blood pressure, and it’s advisable to screen a patient for undiscovered heart disease or cardiovascular risk factors before prescribing stimulants.
Bange F, Le Heuzey MF, Acquaviva E, Delorme R, Mouren MC. Risques cardiovasculaires et conduite à tenir dans le traitement du trouble déficit de l’attention/hyperactivité avec le méthylphénidate [Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate]. Arch Pediatr. 2014 Jan;21(1):108-12. French. doi: 10.1016/j.arcped.2013.11.001. Epub 2013 Dec 3. PMID: 24309201. Link
“Statistically significant pre-post increases of SBP [systolic blood pressure], DBP [diastolic blood pressure] and HR [heart rate] were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.” Interestingly, no significant difference was found based on “type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate.”
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; ADDUCE consortium. 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. 2017 Mar;31(3):199-215. doi: 10.1007/s40263-017-0410-7. PMID: 28236285; PMCID: PMC5336546. Link
“The cumulative body of data showed that ADHD medications cause modest elevations in resting heart rate and blood pressure. Other adverse effects reported with ADHD stimulants included arrhythmia, nonischemic cardiomyopathy, Takotsubo cardiomyopathy, and sudden death. However, such reports did not imply causation, and there was a paucity [lack] of randomized trial evidence addressing long-term safety of ADHD medications, particularly among adults. Further studies are essential…” The article notes that exercise and omega-3 fatty acids are particularly interesting as possible non-pharmacological treatment options.
Torres-Acosta N, O’Keefe JH, O’Keefe CL, Lavie CJ. Cardiovascular Effects of ADHD Therapies: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Aug 18;76(7):858-866. doi: 10.1016/j.jacc.2020.05.081. PMID: 32792083. Link
A study was performed to compare heart rates between stimulant users and non-stimulant users (all adolescents) during exercise on a treadmill. “Adolescent stimulant medication users compared to matched nonusers demonstrated a trend toward decreased HR [heart rate] during submaximal exercise, which is potential evidence of chronic adaptation with stimulant exposure.” The study does not draw any clinical conclusions here, but suggests that this could be a useful diagnostic tool for future studies.
Westover AN, Nakonezny PA, Adinoff B, Brown ES, Halm EA. Impact of Stimulant Medication Use on Heart Rate and Systolic Blood Pressure During Submaximal Exercise Treadmill Testing in Adolescents. J Child Adolesc Psychopharmacol. 2016 Dec;26(10):889-899. doi: 10.1089/cap.2016.0064. Epub 2016 Sep 14. PMID: 27626945; PMCID: PMC5178007. Link
Another exercise study on stimulants found that peak heart rate was lower for stimulant users, and the risk of chronotropic incompetence (heart not keeping up with demand) was about three times higher for stimulant users.
Westover AN, Nakonezny PA, Barlow CE, Vongpatanasin W, Adinoff B, Brown ES, Mortensen EM, Halm EA, DeFina LF. Exercise outcomes in prevalent users of stimulant medications. J Psychiatr Res. 2015 May;64:32-9. doi: 10.1016/j.jpsychires.2015.03.011. Epub 2015 Mar 21. PMID: 25840827; PMCID: PMC4437621. Link
Another study reaffirms that stimulants cause increased heart rate and blood pressure in children, but with unknown clinical effects.
St Amour MD, O’Leary DD, Cairney J, Wade TJ. What is the effect of ADHD stimulant medication on heart rate and blood pressure in a community sample of children? Can J Public Health. 2018 Jun;109(3):395-400. doi: 10.17269/s41997-018-0067-0. Epub 2018 May 7. PMID: 29981090; PMCID: PMC6964398. Link
“There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign.”
Wilens TE, Prince JB, Spencer TJ, Biederman J. Stimulants and sudden death: what is a physician to do? Pediatrics. 2006 Sep;118(3):1215-9. doi: 10.1542/peds.2006-0942. PMID: 16951018. Link
“While many safety concerns have been raised in the use of stimulants, the vast majority of treatment complications are either quickly reversible or easily manageable with appropriate clinical care. The negative consequences of untreated ADHD clearly outweigh the risks of the stimulant medicines when used in an appropriate and careful manner.”
Merkel RL. Safety of stimulant treatment in attention deficit hyperactivity disorder: part II. Expert Opin Drug Saf. 2010 Nov;9(6):917-35. doi: 10.1517/14740338.2010.503238. PMID: 20615078. Link
Children ages 7 to 9 were randomly assigned to various forms of ADHD treatment, including stimulants. “Stimulant treatment did not increase the risk for prehypertension or hypertension over the 10-year period of observation. However, stimulants had a persistent adrenergic effect on heart rate during treatment.”
Vitiello B, Elliott GR, Swanson JM, Arnold LE, Hechtman L, Abikoff H, Molina BS, Wells K, Wigal T, Jensen PS, Greenhill LL, Kaltman JR, Severe JB, Odbert C, Hur K, Gibbons R. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012 Feb;169(2):167-77. doi: 10.1176/appi.ajp.2011.10111705. PMID: 21890793; PMCID: PMC4132884. Link
Electrocardiogram testing was done on children while they were stimulant-free and then again while they were on stimulants. “The main findings of this study were that methylphenidate usage is associated with increases in heart rate (HR) and blood pressure (BP), and that it does not adversely affect HR-corrected QT and JT intervals or cardiac dispersion values.”
Negrao BL, Crafford D, Viljoen M. The effect of sympathomimetic medication on cardiovascular functioning of children with attention-deficit/hyperactivity disorder. Cardiovasc J Afr. 2009 Sep-Oct;20(5):296-9. PMID: 19907802; PMCID: PMC3721264. Link
Complaints related to methylphenidate treatment in children are reviewed. “The more easily quantifiable side effects (e.g., blood pressure [BP], heart rate [HR], height/weight) are mostly transient, dose-dependent, easily rectified with dosage adjustments, and considered minor from a clinical perspective considering the breadth and level of improvement in behavior and cognitive functioning observed in most children.”
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):1107-31. doi: 10.1016/s0272-7358(02)00129-0. PMID: 12436807. Link
Insurance databases were analyzed to determine the risk of cardiovascular events like sudden death, heart attack, and stroke after beginning methylphenidate treatment in adults. Rates of sudden death were about 2 in 1,000 for methylphenidate users and about 1 in 1,000 for non-users; after adjustment, the risk was determined to be about 1.8 times higher for methylphenidate users. The authors say that “the lack of a dose-response relationship suggests that this association may not be a causal one.” In other words, it seems unlikely that methylphenidate was the cause of sudden death in any of those cases. Risk of stroke and heart attack did not differ between users and non-users.
Schelleman H, Bilker WB, Kimmel SE, Daniel GW, Newcomb C, Guevara JP, Cziraky MJ, Strom BL, Hennessy S. Methylphenidate and risk of serious cardiovascular events in adults. Am J Psychiatry. 2012 Feb;169(2):178-85. doi: 10.1176/appi.ajp.2011.11010125. PMID: 22318795. Link
In adults, “Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.”
Schelleman H, Bilker WB, Kimmel SE, Daniel GW, Newcomb C, Guevara JP, Cziraky MJ, Strom BL, Hennessy S. Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults. PLoS One. 2013;8(1):e52991. doi: 10.1371/journal.pone.0052991. Epub 2013 Jan 30. PMID: 23382829; PMCID: PMC3559703. Link
“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.”
Stiefel G, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf. 2010 Oct 1;33(10):821-42. doi: 10.2165/11536380-000000000-00000. PMID: 20812768. Link
“Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.” Healthy-user bias is a research flaw caused by the fact that people who use preventive medications are often wealthier and more health-conscious than people who do not, and therefore have better health outcomes. The authors say this probably explains why occasionally we see fewer cardiovascular problems in stimulant users.
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. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011 Dec 28;306(24):2673-83. doi: 10.1001/jama.2011.1830. Epub 2011 Dec 12. PMID: 22161946; PMCID: PMC3350308. Link
A meta-analysis found that there was a possible association between stimulant use and adverse cardiovascular outcomes in adults, but more study was needed: “Interpretation was limited due to differences in population, cardiovascular outcome selection/ascertainment, and methodology. Accounting for confounding and selection biases in these studies is of particular concern.”
Westover AN, Halm EA. Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review. BMC Cardiovasc Disord. 2012 Jun 9;12:41. doi: 10.1186/1471-2261-12-41. PMID: 22682429; PMCID: PMC3405448. Link
A meta-analysis found that “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.” In other words, no statistically significant association was found, but it’s not impossible for one to exist; if it does, it may be too small to measure without a great deal more study.
Liu H, Feng W, Zhang D. Association of ADHD medications with the risk of cardiovascular diseases: a meta-analysis. Eur Child Adolesc Psychiatry. 2019 Oct;28(10):1283-1293. doi: 10.1007/s00787-018-1217-x. Epub 2018 Aug 24. PMID: 30143889. Link
This study analyzed administrative databases and medical records to determine the relative rate of cardiovascular events in children who use ADHD medication versus children who don’t. “The rate of cardiovascular events in exposed children was very low and in general no higher than that in unexposed control subjects. Because of the low number of events, we have limited ability to rule out relative increases in rate.”
Schelleman H, Bilker WB, Strom BL, Kimmel SE, Newcomb C, Guevara JP, Daniel GW, Cziraky MJ, Hennessy S. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011 Jun;127(6):1102-10. doi: 10.1542/peds.2010-3371. Epub 2011 May 16. PMID: 21576311; PMCID: PMC3387871. Link
“Children/adolescents and adults treated with methylphenidate resulted in significant increases in post- vs. pre-treatment HR [heart rate] and SBP [systolic blood pressure] as compared to placebo. Similarly, children and adolescents treated with atomoxetine had significant increases in post- vs. pre-treatment HR and SBP than those treated with methylphenidate. These findings have potential implications for continuous monitoring of HR and SBP throughout the course of treatment although the risk for adverse cardiac events were insignificant.”
Liang EF, Lim SZ, Tam WW, Ho CS, Zhang MW, McIntyre RS, Ho RC. The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression. Int J Environ Res Public Health. 2018 Aug 20;15(8):1789. doi: 10.3390/ijerph15081789. PMID: 30127314; PMCID: PMC6121294. Link
Cardiovascular measures were taken for children who were newly prescribed methylphenidate, and then again three months later. “After the follow-up period, we observed no abnormal systolic, diastolic, or mean arterial pressure in any of the participants based on their age, height, and gender. However, the mean of all these variables was significantly increased. Mean pulse pressure was also higher than baseline but it wasn’t statistically significant. No significant change was observed in echocardiographic parameters and QT.” The authors recommend further study.
Omidi N, Mojtaba Ghorashi S, Zahedi Tajrishi F, Effatpanah M, Khatami F, Rafie Khorgami M. Effects of methylphenidate on blood pressure, QT-interval, and cardiac output in ADHD diagnosed children: A three months’ follow-up study. Int J Cardiol Heart Vasc. 2021 Jun 2;34:100805. doi: 10.1016/j.ijcha.2021.100805. PMID: 34141860; PMCID: PMC8188377. Link
A UK database of patients aged 2 to 21 was analyzed for cases of sudden death and suicide. “This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.”
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. doi: 10.2165/11317630-000000000-00000. PMID: 19810780. Link
“Several large studies of the very rare phenomenon of sudden death in children have failed to show any convincing association with ADHD treatment. Whether minor increases in HR and BP have a cumulative effect over many years and have a long-term adverse effect on cardiovascular health remains undetermined.”
Awudu GA, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder: an update. Drug Saf. 2014 Sep;37(9):661-76. doi: 10.1007/s40264-014-0201-8. PMID: 25124483. Link
The effects of ADHD drugs on heart health were studied for children and adolescents in Italy. “Treatment with MPH [methylphenidate] and ATX [atomoxetine] in youth appears to have a small but significant impact on the cardiovascular system. The long-term impact of these medications is unknown. Several clinically meaningless ECG alterations were observed mostly in MPH-treated youth. We therefore suggest evaluating cardiovascular risks at baseline.”
Arcieri R, Germinario EA, Bonati M, Masi G, Zuddas A, Vella S, Chiarotti F, Panei P; Italian Attention-Deficit/Hyperactivity Disorder Regional Reference Centers. Cardiovascular measures in children and adolescents with attention-deficit/hyperactivity disorder who are new users of methylphenidate and atomoxetine. J Child Adolesc Psychopharmacol. 2012 Dec;22(6):423-431. doi: 10.1089/cap.2012.0014. PMID: 23362511. Link
“Data from placebo-controlled and open-label extension trials published after 2000 were reviewed, and cardiovascular adverse event data were compared. Both placebo-controlled and open-label extension trials have repeatedly shown stimulant-induced increases in mean blood pressure, heart rate, and QT interval in children, adolescents, and adults. Although these increases seem relatively minor, their existence raises questions regarding whether stimulants could influence the likelihood of sudden death or other serious cardiovascular consequences, especially in patients with underlying heart problems.” The authors recommend an electrocardiogram before starting treatment, as long as it’s not too expensive.
Silva RR, Skimming JW, Muniz R. Cardiovascular safety of stimulant medications for pediatric attention-deficit hyperactivity disorder. Clin Pediatr (Phila). 2010 Sep;49(9):840-51. doi: 10.1177/0009922810368289. PMID: 20693523. Link
Healthcare databases from Ontario, Canada were analyzed to determine the cardiovascular risks of initiating stimulant medication for patients over age 65. “In the primary analysis, stimulant initiation was associated with increased risk of CV [cardiovascular] events at 30 days but not at 180 days or 365 days. In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias and stroke or TIA [transient ischemic attack or mini-stroke] at 30 days.”
Tadrous M, Shakeri A, Chu C, Watt J, Mamdani MM, Juurlink DN, Gomes T. Assessment of Stimulant Use and Cardiovascular Event Risks Among Older Adults. JAMA Netw Open. 2021 Oct 1;4(10):e2130795. doi: 10.1001/jamanetworkopen.2021.30795. Erratum in: JAMA Netw Open. 2021 Nov 1;4(11):e2138512. PMID: 34694389; PMCID: PMC8546494. Link
A meta-analysis of methylphenidate use in children was performed to discover the rate of adverse events. “Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events.” The authors recommend further research and finding ways to determine who may be susceptible to adverse events.
Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, Moreira-Maia CR, Magnusson FL, Holmskov M, Gerner T, Skoog M, Rosendal S, Groth C, Gillies D, Buch Rasmussen K, Gauci D, Zwi M, Kirubakaran R, Håkonsen SJ, Aagaard L, Simonsen E, Gluud C. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev. 2018 May 9;5(5):CD012069. doi: 10.1002/14651858.CD012069.pub2. PMID: 29744873; PMCID: PMC6494554. Link
An FDA-funded cohort study assessed the risk of cardiovascular events in 1.2 million U.S. people ages 2 to 24. “This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low.”
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. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011 Nov 17;365(20):1896-904. doi: 10.1056/NEJMoa1110212. Epub 2011 Nov 1. PMID: 22043968; PMCID: PMC4943074. Link
“It is extremely rare for a child or adolescent receiving stimulant medication to have a serious cardiovascular event during treatment, with the risk appearing similar to groups of children not receiving stimulant medication.” The authors recommend increased monitoring for patients who have cardiovascular risk factors.
Hammerness PG, Perrin JM, Shelley-Abrahamson R, Wilens TE. Cardiovascular risk of stimulant treatment in pediatric attention-deficit/hyperactivity disorder: update and clinical recommendations. J Am Acad Child Adolesc Psychiatry. 2011 Oct;50(10):978-90. doi: 10.1016/j.jaac.2011.07.018. Epub 2011 Sep 3. PMID: 21961773. Link
An expert opinion was written after a review of available research on PubMed. “Long-term cardiovascular risks of stimulants for healthy children and adults with ADHD are limited to minor mean elevations in blood pressure (≤ 7 mmHg) and heart rate (≤ 10 bpm). In a sizeable minority of individuals these elevations are greater and/or reach a clinical threshold. Subjective complaints may also be anticipated during long-term treatment, yet without an increase in serious cardiac outcomes above background rates per age. Future research is needed….”
Hammerness PG, Karampahtsis C, Babalola R, Alexander ME. Attention-deficit/hyperactivity disorder treatment: what are the long-term cardiovascular risks? Expert Opin Drug Saf. 2015 Apr;14(4):543-51. doi: 10.1517/14740338.2015.1011620. Epub 2015 Feb 3. PMID: 25648243. Link
This article notes that stimulants do not continue to provide benefits once treatment is stopped. They increase blood pressure and heart rate, but may be protective against later substance abuse. Additionally, “It would appear that the medical complications associated with amphetamine addiction are not relevant to the therapeutic use of stimulant medication in the treatment of ADHD.”
Poulton A. Long-term outcomes of stimulant medication in attention-deficit hyperactivity disorder. Expert Rev Neurother. 2006 Apr;6(4):551-61. doi: 10.1586/14737175.6.4.551. PMID: 16623654. Link
A health database was analyzed to determine the rates of heart failure and cardiomyopathy among amphetamine users by duration of use. “Heart failure/cardiomyopathy rates in the age groups younger than 22 and 22 to 44 years old were less than 50 per 10,000 person-years, without clear trends by duration of use. The highest rates occurred soon after treatment initiation in the age group 65 years or older, with 1 case per 10.5 person-years of follow-up, or 950 cases per 10,000 person-years, for days 0-90.” Older users were at the highest risk for adverse events, especially soon after starting treatment, and the authors note that some older patients may be predisposed to negative side effects.
Mosholder AD, Taylor L, Mannheim G, Ortendahl L, Woodworth TS, Toh S. Incidence of Heart Failure and Cardiomyopathy Following Initiation of Medications for Attention-Deficit/Hyperactivity Disorder: A Descriptive Study. J Clin Psychopharmacol. 2018 Oct;38(5):505-508. doi: 10.1097/JCP.0000000000000939. PMID: 30102629. Link
Conclusions
I (wrongly) expected to find that stimulants are bad for your heart. I was prepared to reassess my own stimulant use and act to minimize my long-term risk, even if it meant more difficulties with daily symptom management. However, across every study that came up, I found no compelling indications that stimulants cause heart disease, heart attacks, strokes, or other cardiovascular problems (outside of a small increased risk for new users over 65). The few studies that found an association were full of stated caveats and uncertainties. There are reported cases of unexpected heart attacks in stimulant users, but heart attacks are also reported in healthy people who don’t use any drugs at all. It’s not clear that there’s any correlation, let alone a direct causation.
While it’s abundantly proven that Adderall, Ritalin, Vyvanse, and even Strattera cause a “modest increase” in heart rate and systolic blood pressure, there is no evidence that they cause an increase in heart attacks or other adverse heart events over the long term, and studies have found no increased risk over the short and medium term. Even if there are effects at the high end of the confidence interval, the absolute risk is still very small. Whether they use stimulants are not, there’s no reason the average person should be worried about getting a heart attack. Many study authors express speculative concern about possible effects all the same, so some precautions (such as increased monitoring or lower doses) may be valuable if you have a family history of cardiovascular disease. And, of course, overdosing stimulants in order to get high is extremely dangerous.
It seems that some stimulant users do not tolerate intense exercise as well as non-stimulant users. If you have trouble with prolonged cardiovascular exercise, talk with your doctor and maybe consider lower-impact forms of exercise.
The beneficial effects of stimulant medication for people with ADHD are well-known and, for most people, outweigh the negative side effects by a considerable factor. Stimulant users who take their medication as prescribed are far less likely to develop a substance abuse disorder and other mental health issues. Stimulants allow people with ADHD to enjoy a higher quality of life and greater success in school, work, and relationships. It’s also worth noting that many people with ADHD find it extremely hard to exercise and eat well, and report that stimulants make it possible for them to control their impulses and make better health-related decisions.