Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder

Abstract

Background Psychostimulants and atomoxetine have been shown to increase blood pressure, heart rate, and QT interval in children and adolescents; however, based on current literature, it is unclear if these "attention-deficit/hyperactivity disorder (ADHD) medications" are also associated with serious cardiovascular (SCV) events. We addressed this question in commonly exposed groups of children and adolescents with either ADHD or autism spectrum disorder (ASD). Methods Using commercial (years 2000-2016) and Medicaid (years 2012-2016) administrative claims data from the United States (US), we conducted two case-control studies, nested within respective cohorts of ADHD and ASD children aged 3-18 years. We defined cases by a composite outcome of stroke, myocardial infarction, or serious cardiac arrhythmia. For each case, we matched ten controls on age, sex, and insurance type. We conducted conditional logistic regression models to test associations between SCV outcomes and a primary exposure definition of current ADHD medication use. Additionally, we controlled for resource use, cardiovascular and psychiatric comorbidities, and use of medications in a variety of sensitivity analyses. Results We identified 2,240,774 children for the ADHD cohort and 326,221 children for the ASD cohort. For ADHD, 33.9% of cases (63 of 186) versus 32.2% of controls (598 of 1860) were exposed, which yielded an odds ratio (OR) and 95% confidence interval (CI) of 1.08 (0.78-1.49). For ASD, 12.5% of cases (6 of 48) versus 22.1% of controls (106 of 480) were exposed ]. Covariate-adjusted results and results for individual outcomes and other exposure definitions were consistent with no increased risk of SCV events. Conclusion Using large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications. Key PointsAttention-deficit/hyperactivity disorder (ADHD) medications increase blood pressure, heart rate, and QT interval. It is unclear if they increase serious cardiovascular event rates.Current literature is based mainly on pre-2006 data and small samples, and has not considered subgroups of children with different medical diagnoses.Using data from 2000-2016, for US children aged 3-18 years, we found no evidence of increased serious cardiovascular risk in those exposed to ADHD medications.Findings were consistent for children with either ADHD or autism spectrum disorder.Presentation Information A partly similar analysis to the one shown here (ASD cohort only) has been accepted for poster presentation at the

The use of attention-deficit hyperactivity disorder medications in cardiac disease

“…In contrast, the increased risk of MI or stroke was not found to be significantly higher in those who recently started stimulants or atomoxetine in half a million participants . Moreover, most studies did not find any association between atomoxetine and MI or stroke (Holick et al, 2009;Schelleman et al, 2012;Houghton et al, 2020). However, stimulants/atomoxetine might increase the risk of a transient ischemic attack in adults (Holick et al, 2009) which was not observed for children.…”

The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review

“…Elevated blood pressure and heart rate have been reported in patients with atomoxetine therapy ( 101 ). However, the effects of most patients on the cardiovascular system have no clinical significance ( 101 , 128 , 129 ). Hammerness et al ( 130 ) found a statistically significant increase in heart rate in 6- and 7-year-old children with ADHD who received atomoxetine compared with placebo ( p < 0.001).…”

Effects of methylphenidate on blood pressure, QT-interval, and cardiac output in ADHD diagnosed children: A three months’ follow-up study

“…Of note, the use of stimulants did not cause any significant changes in adverse cardiovascular events in children and adults [38] , [44] , [54] . Despite non-pathological increases in BP, HR, and QT interval, because increased BP, HR, and QT interval are associate with cardiovascular morbidity and mortality during adulthood so pediatric patients treated with ADHD medication need to be monitored for HR and BP, closely and regularly.…”

“…Reports related to sudden deaths of patients, mainly children, treated by these drugs have raised the question of whether these medications increase the risk of cardiovascular events [37] . On the other hand, numerous massive cohort studies have not demonstrated any increased risk of life-threatening cardiovascular events among children treated by stimulants compared with the general population [38] . However, sudden death remains an extremely rare event and not be attributed to methylphenidate as there is no clear evidence supporting this association [39] .…”