Cited by 49Attention Deficit Hyperactivity DisorderSubstance Abuse Treatment and OutcomesCoffee research and impacts

Assessment of stimulant use and cardiovascular event risks among older adults

Open access
Tadrous, Mina, Shakeri, Ahmad, Chu, Cherry, Watt, Jennifer, Mamdani, Muhammad M., Juurlink, David N., Gomes, Tara·2021·JAMA Network Open

Abstract

Importance: Use of stimulants continues to increase among older adults for a variety of indications. An association between stimulant use and increased risk of cardiovascular (CV) events has been established among children and young adults, but few studies have explored the risk of CV events among older patients, a group with increased baseline risk. Objective: To evaluate the association between stimulant use and risk of CV events among older adults. Design, Setting, and Participants: This propensity score-matched cohort study, with 4 nonusers per 1 user, was conducted from July 1, 2017, to June 27, 2019, using data from population-based health care databases from Ontario, Canada, from January 1, 2002, to December 31, 2016. Included individuals were outpatients aged 66 years or older. Exposures: Initiation of a prescription stimulant. Main Outcomes and Measures: The primary outcome was a CV event, defined as a composite of emergency department visit or hospitalization for myocardial infarction, stroke or transient ischemic attack (TIA), or ventricular arrhythmia. Risk of CV event was assessed at 30 days, 180 days, and 365 days after initiation of stimulants from Cox proportional hazard models. A secondary analysis assessed each component of the primary outcome separately. Results: Among 6457 older adults who initiated a prescription stimulant (ie, the exposed group) and 24 853 older adults who did not initiate such treatment (ie, the unexposed group), the distribution of baseline patient characteristics was well balanced after matching (sex: 3173 [49.1%] men vs 12 112 [48.7%] men; standardized difference, 0.01; median [IQR] age: 74 [69-80] years vs 74 [69-80] years; standardized difference, 0.01). Within this cohort, there were 932 CV events during the 365-day follow-up (5.11 events per 100 person-years among individuals who initiated stimulants). In the primary analysis, stimulant initiation was associated with increased risk of CV events at 30 days (hazard ratio [HR], 1.4; 95% CI, 1.1-1.8) but not at 180 days (HR, 1.2; 95% CI, 0.9-1.6) or 365 days (HR, 1.0; 95% CI, 0.6 to 1.8). In the secondary analysis, stimulant initiation was associated with increased risk of ventricular arrhythmias (HR, 3.0; 95% CI, 1.1-8.7) and stroke or TIA (HR, 1.6; 95% CI, 1.1-2.1) at 30 days. Conclusions and Relevance: This cohort study found that stimulant use was associated with an early increase in CV events among older adults with no association for long-term use.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jamanetworkopen.2021.30795

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A washout period of at least 18 months before the first ADHD medication dispensation was used to establish ADHD medication status.

    “Jan 1, 2007, was chosen as the start date to allow a washout period of at least 18 months before the first ADHD medication dispensation date to establish ADHD medication status,10 which was defined as no ADHD drug dispensations in the 18 months before treatment initiation.”

    From Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals (2025) · cites this paper as [10]

    The Methods (Cohort Definition; page not provided) define treatment initiation as no other stimulant prescription in the previous 365 days, not no ADHD medication dispensation in the previous 18 months. The study’s accrual window also began January 1, 2002, rather than January 1, 2007. (LLM, conf=0.89)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. [4]Zito JM, Safer DJ, DosReis S,. Psychotropic practice patterns for youth: a 10-year perspective. Arch Pediatr Adolesc Med. 2003; 157(1): 17- 25. doi: 10.1001/archpedi.157.1.17 12517190 · DOI
  2. [5]Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015; 314(17): 1818- 1831. doi: 10.1001/jama.2015.13766 26529160 PMC4752169 · DOI · Paper page
  3. [6]Herrmann N, Rothenburg LS, Black SE,. Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge. J Clin Psychopharmacol. 2008; 28(3): 296- 301. doi: 10.1097/JCP.0b013e318172b479 18480686 · DOI
  4. [7]Homsi J, Nelson KA, Sarhill N,. A phase II study of methylphenidate for depression in advanced cancer. Am J Hosp Palliat Care. 2001; 18(6): 403- 407. doi: 10.1177/104990910101800610 11712722 · DOI
  5. [8]Lanctôt KL, Chau SA, Herrmann N,. Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial. Int Psychogeriatr. 2014; 26(2): 239- 246. doi: 10.1017/S1041610213001762 24169147 PMC3927455 · DOI
  6. [9]Gong S, Sheng P, Jin H,. Effect of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis. PLoS One. 2014; 9(1): e84391. doi: 10.1371/journal.pone.0084391 24416225 PMC3885551 · DOI
  7. [10]Sarhill N, Walsh D, Nelson KA, Homsi J, LeGrand S, Davis MP. Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study. Am J Hosp Palliat Care. 2001; 18(3): 187- 192. doi: 10.1177/104990910101800310 11406895 · DOI
  8. [12]Prommer E. Methylphenidate: established and expanding roles in symptom management. Am J Hosp Palliat Care. 2012; 29(6): 483- 490. doi: 10.1177/1049909111427029 22144657 · DOI
  9. [13]Wallace AE, Kofoed LL, West AN. Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients. Am J Psychiatry. 1995; 152(6): 929- 931. doi: 10.1176/ajp.152.6.929 7755127 · DOI
  10. [14]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; 23(6): 534- 541. doi: 10.1016/j.euroneuro.2012.06.011 22796229 PMC3488604 · DOI
  11. [15]Westover AN, Halm EA. Do prescription stimulants increase the risk of adverse cardiovascular events?: a systematic review. BMC Cardiovasc Disord. 2012; 12: 41. doi: 10.1186/1471-2261-12-41 22682429 PMC3405448 · DOI
  12. [16]Torgersen T, Gjervan B, Lensing MB, Rasmussen K. Optimal management of ADHD in older adults. Neuropsychiatr Dis Treat. 2016; 12: 79- 87. doi: 10.2147/NDT.S59271 26811680 PMC4712975 · DOI · Paper page
  13. [17]Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018; 8(8): CD007813. doi: 10.1002/14651858.CD007813.pub3 30091808 PMC6513464 · DOI · Paper page
  14. [19]Black JC, Bau GE, Iwanicki JL, Dart RC. Association of medical stimulants with mortality in the US from 2010 to 2017. JAMA Intern Med. 2021; 181(5): 707- 709. doi: 10.1001/jamainternmed.2020.7850 33523100 PMC7851755 · DOI
  15. [20]Westover AN, Nakonezny PA, Winhusen T, Adinoff B, Vongpatanasin W. Risk of methylphenidate-induced prehypertension in normotensive adult smokers with attention deficit hyperactivity disorder. J Clin Hypertens (Greenwich). 2013; 15(2): 124- 132. doi: 10.1111/jch.12039 23339731 PMC3556994 · DOI
  16. [21]Waksman J, Taylor RN Jr, Bodor GS, Daly FFS, Jolliff HA, Dart RC. Acute myocardial infarction associated with amphetamine use. Mayo Clin Proc. 2001; 76(3): 323- 326. doi: 10.4065/76.3.323 11243281 · DOI
  17. [22]Sinha A, Lewis O, Kumar R, Yeruva SLH, Curry BH. Amphetamine abuse related acute myocardial infarction. Case Rep Cardiol. 2016; 2016: 7967851. doi: 10.1155/2016/7967851 26998366 PMC4779519 · DOI
  18. [24]Schelleman H, Bilker WB, Kimmel SE,. Methylphenidate and risk of serious cardiovascular events in adults. Am J Psychiatry. 2012; 169(2): 178- 185. doi: 10.1176/appi.ajp.2011.11010125 22318795 · DOI
  19. [25]Schelleman H, Bilker WB, Kimmel SE,. Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults. PLoS One. 2013; 8(1): e52991. doi: 10.1371/journal.pone.0052991 23382829 PMC3559703 · DOI
  20. [26]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; 38(5): 505- 508. doi: 10.1097/JCP.0000000000000939 30102629 · DOI
  21. [27]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; 76(7): 858- 866. doi: 10.1016/j.jacc.2020.05.081 32792083 · DOI
  22. [29]Rassen JA, Glynn RJ, Brookhart MA, Schneeweiss S. Covariate selection in high-dimensional propensity score analyses of treatment effects in small samples. Am J Epidemiol. 2011; 173(12): 1404- 1413. doi: 10.1093/aje/kwr001 21602301 PMC3145392 · DOI
  23. [30]Schneeweiss S. Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf. 2006; 15(5): 291- 303. doi: 10.1002/pds.1200 16447304 · DOI
  24. [31]Hall R, Mondor L, Porter J, Fang J, Kapral MK. Accuracy of administrative data for the coding of acute stroke and TIAs. Can J Neurol Sci. 2016; 43(6): 765- 773. doi: 10.1017/cjn.2016.278 27426016 · DOI
  25. [33]Gomes T, Juurlink DN, Ho JMW, Schneeweiss S, Mamdani MM. Risk of serious falls associated with oxybutynin and tolterodine: a population based study. J Urol. 2011; 186(4): 1340- 1344. doi: 10.1016/j.juro.2011.05.077 21855905 · DOI
  26. [34]Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011; 10(2): 150- 161. doi: 10.1002/pst.433 20925139 PMC3120982 · DOI · Paper page
  27. [35]Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011; 46(3): 399- 424. doi: 10.1080/00273171.2011.568786 21818162 PMC3144483 · DOI · Paper page
  28. [36]Vigod SN, Gomes T, Wilton AS, Taylor VH, Ray JG. Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ. 2015; 350: h2298. doi: 10.1136/bmj.h2298 25972273 PMC4430156 · DOI
  29. [38]Mamdani M, Sykora K, Li P,. Reader’s guide to critical appraisal of cohort studies: 2. assessing potential for confounding. BMJ. 2005; 330(7497): 960- 962. doi: 10.1136/bmj.330.7497.960 15845982 PMC556348 · DOI
  30. [39]Chung W, Jiang SF, Paksarian D,. Trends in the prevalence and incidence of attention-deficit/hyperactivity disorder among adults and children of different racial and ethnic groups. JAMA Netw Open. 2019; 2(11): e1914344. doi: 10.1001/jamanetworkopen.2019.14344 31675080 PMC6826640 · DOI
  31. [40]Anderson KN, Ailes EC, Danielson M,. Attention-deficit/hyperactivity disorder medication prescription claims among privately insured women aged 15-44 years—United States, 2003-2015. MMWR Morb Mortal Wkly Rep. 2018; 67(2): 66- 70. doi: 10.15585/mmwr.mm6702a3 29346342 PMC5772805 · DOI
  32. [42]Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009; 25(4): 563- 577, vii. doi: 10.1016/j.cger.2009.07.007 19944261 PMC2797320 · DOI
  33. [43]Roccaforte WH, Burke WJ. Use of psychostimulants for the elderly. Hosp Community Psychiatry. 1990; 41(12): 1330- 1333. 1980482
  34. [44]Cooper WO, Habel LA, Sox CM,. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011; 365(20): 1896- 1904. doi: 10.1056/NEJMoa1110212 22043968 PMC4943074 · DOI · Paper page
  35. [46]Shin JY, Roughead EE, Park BJ, Pratt NL. Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. BMJ. 2016; 353: i2550. doi: 10.1136/bmj.i2550 27245699 PMC4887614 · DOI · Paper page
  36. [48]Olfson M, Huang C, Gerhard T,. Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012; 51(2): 147- 156. doi: 10.1016/j.jaac.2011.11.008 22265361 PMC3266532 · DOI
  37. [49]Sinha A, Lewis O, Kumar R, Yeruva SLH, Curry BH. Adult ADHD medications and their cardiovascular implications. Case Rep Cardiol. 2016; 2016: 2343691. doi: 10.1155/2016/2343691 27579185 PMC4992783 · DOI
  38. [50]Suchard JR, Curry SC. Methamphetamine toxicity. Pediatr Emerg Care. 1999; 15(4): 306. doi: 10.1097/00006565-199908000-00020 10460094 · DOI
  39. [51]Gajria K, Lu M, Sikirica V,. Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder—a systematic literature review. Neuropsychiatr Dis Treat. 2014; 10: 1543- 1569. 25187718 PMC4149449
  40. [52]Lohr WD, Wanta JW, Baker M,. Intentional discontinuation of psychostimulants used to treat ADHD in youth: a review and analysis. Front Psychiatry. 2021; 12: 642798. doi: 10.3389/fpsyt.2021.642798 33959050 PMC8093505 · DOI

Cited by

Sorted by citations

Authors
Tadrous, M., Shakeri, A., Chu, C., Watt, J., Mamdani, M. M., Juurlink, D. N., & Gomes, T.
Affiliations
  • University of Toronto (CA)
  • Women's College Hospital (CA)
  • Unity Health Toronto (CA)
  • Sunnybrook Health Science Centre (CA)
Corresponding author
Tadrous, Mina
Venue
JAMA Network Open
Published
2021-10-25
Volume
4
Issue
10
Pages
e2130795
ISSN
2574-3805 (ISSN-L)
OpenAlex
W3210157719
Cited by
49
References
8
Citations by year
2026: 12 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 5 · 2021: 1
FWCI
4.84
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • JAMA Network Open (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
Keywords
stimulant medication, older adults, cardiovascular events, myocardial infarction, stroke, transient ischemic attack, ventricular arrhythmias, cardiovascular risk, adverse drug reactions, propensity score matching, hospitalization and emergency department visits, cardiovascular disease prevalence
MeSH terms
Aged, Aged, 80 and over, Central Nervous System Stimulants, Cerebrovascular Disorders, Female, Humans, Male, Cohort Studies, Propensity Score

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review