No statistically significant association exists between attention-deficit/hyperactivity disorder (ADHD) medication use and the risk for cardiovascular disease (CVD) among any age group, according to study findings published in the Journal of the American Medical Association Network Open.
Researchers sourced data from the Embase, PsycINFO, PubMed, and Web of Science databases up to May 1, 2022. They found 19 observational studies published between 2007 and 2021 that included more than 3.9 million participants (39.1% women/girls) and examined the association between ADHD medications and CVD risks.
Data was extracted by independent reviewers and pooled using random-effects models. Study quality was assessed using the Good Research for Comparative Effectiveness checklist. Of the included studies, 14 were cohort studies. Median follow-up time across all studies was 1.5 years (range, 0.25-9.5 years). Randomized clinical trials, animal research, review articles, reports, and conference abstracts were excluded, as were studies lacking a comparator group or those with abuse or misuse of ADHD medication as the exposure.
The primary outcome was any cardiovascular event (ie, heart failure, cardiac arrest, tachyarrhythmia, venous thromboembolism, hypertension, cerebrovascular disease, and ischemic heart disease). Secondary outcomes assessed the association differences by types of ADHD medication, sex, age, preexisting CVD conditions, and types of cardiovascular events.
Researchers found the pooled adjusted relative risk (RR) showed no significant association between ADHD medication use and any CVD among older adults (RR, 1.59; 95% CI, 0.62-4.05), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or children and adolescents (RR, 1.18; 95% CI, 0.91-1.53).
There were no statistically significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97).
No statistically significant association related to cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65), or cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72) was found.
Researchers found no associations with any CVD in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16) or in those with no history of CVD (RR, 0.99; 95% CI, 0.73-1.33), or in patients who are women (RR, 1.88; 95% CI, 0.43-8.24), or in patients who are men (RR, 1.08; 95% CI, 0.32-3.67).
Between-study heterogeneity was high and significant (Cochran Q=292.7; P <.001; I2= 93.2%), other than the analysis on cerebrovascular diseases (P-value associated with the Cochran Q statistic of heterogeneity =.14). They found no evidence of publication bias.
Limitations of the study include significant heterogeneity, the inability to compare associations with specific ADHD medications, and a lack of generalizability.
Study authors conclude, “[T]his meta-analysis suggested no statistically significant association between ADHD medication use and the risk of any cardiovascular events across age groups, although a modest risk increase could not be excluded, especially for the risk of cardiac arrest or tachyarrhythmias.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Zhang L, Yao H, Li L, et al. Risk of cardiovascular diseases associated with medications used in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. JAMA Netw Open. Published online November 23, 2022. doi:10.1001/jamanetworkopen.2022.43597