{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:09:50Z","timestamp":1793876990305,"version":"4.7.0"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"\n Importance<\/jats:title>\n Use of attention-deficit\/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the association between long-term use of ADHD medication and the risk of CVD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Cumulative duration of ADHD medication use up to 14 years.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to \u22641 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to \u22642 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to \u22643 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to \u22645 years: AOR, 1.27 [95% CI, 1.17-1.39]; and &amp;gt;5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to \u22645 years: AOR, 1.72 [95% CI, 1.51-1.97] and &amp;gt;5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to \u22645 years: AOR, 1.65 [95% CI, 1.11-2.45] and &amp;gt;5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged &amp;lt;25 years) and adults (aged \u226525 years).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2023.4294","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T11:35:47Z","timestamp":1700652947000},"page":"178","source":"Crossref","is-referenced-by-count":148,"title":["Attention-Deficit\/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases"],"prefix":"10.1001","volume":"81","author":[{"given":"Le","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Andell","sequence":"additional","affiliation":[{"name":"Unit of Cardiology, Heart and Vascular Division, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Garcia-Argibay","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick D.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Applied Health Science, School of Public Health, Indiana University, Bloomington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"D\u2019Onofrio","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Psychological and Brain Sciences, Indiana University, Bloomington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabell","family":"Brikell","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Kuja-Halkola","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lichtenstein","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Johnell","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"School of Medical Sciences, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"yoi230086r2","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1192\/bjp.bp.107.048827","article-title":"Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis.","volume":"194","author":"Simon","year":"2009","journal-title":"Br J Psychiatry"},{"issue":"11","key":"yoi230086r3","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1056\/NEJMra1917069","article-title":"Pharmacologic treatment of attention deficit-hyperactivity disorder.","volume":"383","author":"Cortese","year":"2020","journal-title":"N Engl J Med"},{"issue":"10","key":"yoi230086r4","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/S2215-0366(18)30293-1","article-title":"Trends in attention-deficit hyperactivity disorder medication use: a retrospective observational study using population-based databases.","volume":"5","author":"Raman","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"9","key":"yoi230086r5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","article-title":"Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.","volume":"5","author":"Cortese","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"5","key":"yoi230086r6","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.biopsych.2019.04.009","article-title":"Risks and benefits of attention-deficit\/hyperactivity disorder medication on behavioral and neuropsychiatric outcomes: a qualitative review of pharmacoepidemiology studies using linked prescription databases.","volume":"86","author":"Chang","year":"2019","journal-title":"Biol Psychiatry"},{"issue":"11","key":"yoi230086r7","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009885.pub2","article-title":"Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).","volume":"2015","author":"Storeb\u00f8","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"issue":"7","key":"yoi230086r8","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.jacc.2020.05.081","article-title":"Cardiovascular effects of ADHD therapies: JACC review topic of the week.","volume":"76","author":"Torres-Acosta","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"yoi230086r9","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.euroneuro.2012.06.011","article-title":"Meta-analysis of increased heart rate and blood pressure associated with CNS stimulant treatment of ADHD in adults.","volume":"23","author":"Mick","year":"2013","journal-title":"Eur Neuropsychopharmacol"},{"issue":"20","key":"yoi230086r10","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1056\/NEJMoa1110212","article-title":"ADHD drugs and serious cardiovascular events in children and young adults.","volume":"365","author":"Cooper","year":"2011","journal-title":"N Engl J Med"},{"issue":"24","key":"yoi230086r11","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1001\/jama.2011.1830","article-title":"ADHD medications and risk of serious cardiovascular events in young and middle-aged adults.","volume":"306","author":"Habel","year":"2011","journal-title":"JAMA"},{"issue":"11","key":"yoi230086r13","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.43597","article-title":"Risk of cardiovascular diseases associated with medications used in attention-deficit\/hyperactivity disorder: a systematic review and meta-analysis.","volume":"5","author":"Zhang","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"5","key":"yoi230086r14","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S2215-0366(23)00042-1","article-title":"Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.","volume":"10","author":"Man","year":"2023","journal-title":"Lancet Psychiatry"},{"issue":"3","key":"yoi230086r15","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/wps.v21.3","article-title":"Attention-deficit\/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population-based cohort study.","volume":"21","author":"Li","year":"2022","journal-title":"World Psychiatry"},{"issue":"2","key":"yoi230086r16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1017\/S003329170500471X","article-title":"The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies.","volume":"36","author":"Faraone","year":"2006","journal-title":"Psychol Med"},{"issue":"5","key":"yoi230086r17","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1177\/00048674221114782","article-title":"Patterns of attention deficit hyperactivity disorder medicine use in the era of new non-stimulant medicines: a population-based study among Australian children and adults (2013-2020).","volume":"57","author":"Bruno","year":"2023","journal-title":"Aust N Z J Psychiatry"},{"issue":"11","key":"yoi230086r18","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research.","volume":"24","author":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"issue":"1","key":"yoi230086r19","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish National Inpatient Register.","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"issue":"7","key":"yoi230086r20","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/pds.v16:7","article-title":"The new Swedish Prescribed Drug Register\u2014opportunities for pharmacoepidemiological research and experience from the first six months.","volume":"16","author":"Wettermark","year":"2007","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"4","key":"yoi230086r21","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s10654-019-00511-8","article-title":"The Longitudinal Integrated Database for Health Insurance and Labour Market studies (LISA) and its use in medical research.","volume":"34","author":"Ludvigsson","year":"2019","journal-title":"Eur J Epidemiol"},{"issue":"9","key":"yoi230086r22","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","article-title":"The Swedish cause of death register.","volume":"32","author":"Brooke","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"yoi230086r23","doi-asserted-by":"publisher","first-page":"k3532","DOI":"10.1136\/bmj.k3532","article-title":"The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE).","volume":"363","author":"Langan","year":"2018","journal-title":"BMJ"},{"issue":"10","key":"yoi230086r24","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.30795","article-title":"Assessment of stimulant use and cardiovascular event risks among older adults.","volume":"4","author":"Tadrous","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"4","key":"yoi230086r25","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1136\/ebmental-2020-300231","article-title":"Prediction of treatment dosage and duration from free-text prescriptions: an application to ADHD medications in the Swedish Prescribed Drug Register.","volume":"24","author":"Zhang","year":"2021","journal-title":"Evid Based Ment Health"},{"key":"yoi230086r26","doi-asserted-by":"publisher","first-page":"c2582","DOI":"10.1136\/bmj.c2582","article-title":"Nested case-control studies.","volume":"340","author":"Sedgwick","year":"2010","journal-title":"BMJ"},{"issue":"9949","key":"yoi230086r27","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/S0140-6736(14)60379-2","article-title":"Antipsychotics, mood stabilisers, and risk of violent crime.","volume":"384","author":"Fazel","year":"2014","journal-title":"Lancet"},{"issue":"6","key":"yoi230086r30","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1089\/cap.2014.0020","article-title":"Cardiovascular safety of stimulants in children with attention-deficit\/hyperactivity disorder: a nationwide prospective cohort study.","volume":"24","author":"Dalsgaard","year":"2014","journal-title":"J Child Adolesc Psychopharmacol"},{"issue":"10","key":"yoi230086r31","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1111\/jce.2015.26.issue-10","article-title":"Long-QT syndrome and therapy for attention deficit\/hyperactivity disorder.","volume":"26","author":"Zhang","year":"2015","journal-title":"J Cardiovasc Electrophysiol"},{"key":"yoi230086r32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.euroneuro.2022.09.001","article-title":"Long-term methylphenidate exposure and 24-hours blood pressure and left ventricular mass in adolescents and young adults with attention deficit hyperactivity disorder.","volume":"64","author":"Buitelaar","year":"2022","journal-title":"Eur Neuropsychopharmacol"},{"issue":"4","key":"yoi230086r33","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00702-022-02583-5","article-title":"Long-term changes in serum levels of lipoproteins in children and adolescents with attention-deficit\/hyperactivity disorder (ADHD).","volume":"130","author":"Huber","year":"2023","journal-title":"J Neural Transm (Vienna)"},{"issue":"7","key":"yoi230086r34","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1177\/0091270009336736","article-title":"Methylphenidate has positive hypocholesterolemic and hypotriglyceridemic effects: new data.","volume":"49","author":"Charach","year":"2009","journal-title":"J Clin Pharmacol"},{"issue":"3","key":"yoi230086r35","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s40263-017-0410-7","article-title":"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.","volume":"31","author":"Hennissen","year":"2017","journal-title":"CNS Drugs"},{"issue":"12","key":"yoi230086r36","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.jaac.2022.03.034","article-title":"Efficacy and safety of lisdexamfetamine in preschool children with attention-deficit\/hyperactivity disorder.","volume":"61","author":"Childress","year":"2022","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"8","key":"yoi230086r37","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.3390\/ijerph15081789","article-title":"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.","volume":"15","author":"Liang","year":"2018","journal-title":"Int J Environ Res Public Health"},{"issue":"3","key":"yoi230086r38","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/acps.2018.137.issue-3","article-title":"Gender differences in psychiatric comorbidity: a population-based study of 40 000 adults with attention deficit hyperactivity disorder.","volume":"137","author":"Solberg","year":"2018","journal-title":"Acta Psychiatr Scand"},{"issue":"9","key":"yoi230086r39","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/S2215-0366(21)00171-1","article-title":"Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study.","volume":"8","author":"Du Rietz","year":"2021","journal-title":"Lancet Psychiatry"},{"issue":"2","key":"yoi230086r40","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.phrs.2006.11.001","article-title":"Gender differences in drug responses.","volume":"55","author":"Franconi","year":"2007","journal-title":"Pharmacol Res"},{"issue":"14","key":"yoi230086r41","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1177\/070674370605101408","article-title":"Adverse cardiovascular events in antidepressant trials involving high-risk patients: a systematic review of randomized trials.","volume":"51","author":"Swenson","year":"2006","journal-title":"Can J Psychiatry"},{"key":"yoi230086r42","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/647476","article-title":"Risk of mortality (including sudden cardiac death) and major cardiovascular events in users of olanzapine and other antipsychotics: a study with the General Practice Research Database.","volume":"2013","author":"Jones","year":"2013","journal-title":"Cardiovasc Psychiatry Neurol"},{"key":"yoi230086r1","first-page":"15020","article-title":"Attention-deficit\/hyperactivity disorder.","volume-title":"Nat Rev Dis Primers","author":"Faraone","year":"2015"},{"key":"yoi230086r12","first-page":"i2550","article-title":"Cardiovascular safety of methylphenidate among children and young people with attention-deficit\/hyperactivity disorder (ADHD): nationwide self controlled case series study.","volume-title":"BMJ","author":"Shin","year":"2016"},{"key":"yoi230086r28","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3462-1","volume-title":"Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis","author":"Harrell","year":"2001"},{"key":"yoi230086r29","unstructured":"WHO Collaborating Centre for Drug Statistics Methodology. Defined daily dose. Accessed August 9, 2023. https:\/\/www.whocc.no\/ddd\/definition_and_general_considera\/"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2811812\/jamapsychiatry_zhang_2023_oi_230086_1706192516.35527.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T11:04:27Z","timestamp":1707303867000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2811812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,1]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2023.4294","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2,1]]}}}