Affiliation:
1. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden
2. School of Medical Sciences, Örebro University, Örebro, Sweden
3. Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
4. Heart and Vascular Division, Karolinska University Hospital, Stockholm, Sweden
5. Department of Psychological and Brain Sciences, Indiana University, Bloomington
6. Centre for Innovation in Mental Health-Developmental Lab, School of Psychology, University of Southampton and NHS Trust, Southampton, United Kingdom
7. Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York
8. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
Abstract
ImportanceUse of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.ObjectiveTo provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).Data SourcesPubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.Study SelectionObservational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.Data Extraction and SynthesisIndependent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.Main Outcomes and MeasuresThe outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.ResultsNineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.Conclusions and RelevanceThis meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.
Publisher
American Medical Association (AMA)