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Hi! David Rosenberg here for the Psychopharmacology Institute. In this CAP—or Child and Adolescent Psychiatry—Smart Take, we will examine the risk of cardiovascular diseases associated with medications used to treat ADHD, which has continued to increase across all age groups. So, this is a timely analysis given continued concerns regarding the cardiovascular safety of the medicines we use to treat ADHD. The authors conducted a comprehensive meta-analysis of nearly 4 million children, adolescents, and adults. The specific outcomes they looked at were any cardiovascular incidents, such as cerebrovascular disease, heart failure, heart disease, cardiac arrest, hypertension, tachyarrhythmias, and venous thromboembolism.
So, I know you are all eager to know what they found. Well, let’s start with the good news. No significant associations existed between medicines used to treat ADHD and cerebrovascular disease. Specifically, there were no significant associations with cardiovascular disease for stimulant or nonstimulant medicines. So, we are feeling good now, right? This is good news. Well, hold on. The risk of cardiovascular incidence associated with using medicines to treat ADHD did appear to be higher in patients with preexisting cardiovascular disease than in patients with no cardiovascular disease history. However, these findings were not statistically significant—still something we need to keep in mind and be on the lookout for. Remember that the FDA labeling for medicines used to treat ADHD has a warning on their use in patients with structural cardiac abnormalities or serious cardiac disease.
So, although this meta-analysis provides some reassurance on cardiovascular risk with ADHD medicines, there are still possible modest increased risks or associations where we need further study. The meta-analysis could not precisely determine the risk of preexisting cardiovascular disease. Is there a potential for increased or modest risk of cardiac arrest or tachyarrhythmias? Females with ADHD have been notoriously understudied and have different comorbidities than males. Moreover, most were male, even in this sample of nearly 4 million patients. So, this is an area requiring further study in terms of the risk of cardiovascular disease. So, a little confusing, right? What is the bottom line? In my clinical experience, in the literature overall, and the vast majority of instances, when we use medicines to treat ADHD correctly and prescribe them when indicated, they pose a minimal cardiovascular risk.
The most commonly used medicines to treat ADHD, stimulants; they are bread-and-butter medications that, when prescribed correctly, do enormous good and are very well tolerated. Stimulant and nonstimulant medicines can be associated with cardiovascular events, blood pressure, and pulse changes. Teasing apart problems of underlying illnesses and comorbidity, the impact of the illness itself on physical well-being and sleep also needs to be kept in mind. However, we must also remember Hippocrates and our oath not to harm, safety first. In all patients, I recommend getting vital signs, blood pressure, and pulse at baseline and then at each visit going forward for as long as the patient is on ADHD medicine. For patients with preexisting cardiovascular disease, added caution is needed. I recommend getting an ECG at baseline and more frequently if there are any concerns of adverse sequelae.
Now, I also recommend getting a cardiology consult before starting the medicines. I also realize that working in a large hospital system, as I do, is much easier than it is for some. However, for your and your patient’s and parents’ peace of mind, it is worth it when you can check blood pressure, pulse, and ECG and consult with a cardiologist or, at the very least, the patient’s primary care physician.
Abstract
Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
Le Zhang, Honghui Yao, Lin Li, Ebba Du Rietz, Pontus Andell, Miguel Garcia-Argibay, Brian M D’Onofrio, Samuele Cortese, Henrik Larsson, Zheng Chang
Importance: Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.
Objective: To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).
Data sources: PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.
Study selection: Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.
Data extraction and synthesis: Independent 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 measures: The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.
Results: Nineteen 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 relevance: This 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.
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Reference
Zhang, L., Yao, H., Li, L., Du Rietz, E., Andell, P., Garcia-Argibay, M., D’Onofrio, B. M., Cortese, S., Larsson, H., & Chang, Z. (2022). Risk of cardiovascular diseases associated with medications used in attention-deficit/Hyperactivity disorder. JAMA Network Open, 5(11), e2243597.
