Could ADHD Medication Increase Cardiovascular Disease Risk?

A new study found that long-term users of attention-deficit/hyperactivity disorder (ADHD) medication face a higher risk of developing cardiovascular disease (CVD). Findings were published in JAMA Psychiatry.¹

Study investigators found a 4% increase in CVD risk for each year of medication use, underscoring the importance of considering both the benefits and risks of long-term ADHD treatment decisions.

Over the past few decades, the use of ADHD medication has risen dramatically in both children and adults. In 2016, children taking ADHD medication represented 1 out of 20 of all children in the US.² Although research has established the effectiveness of ADHD medication, concerns have emerged regarding its cardiovascular safety profile due to reported increases in heart rate and blood pressure associated with its use.

While investigators have begun to explore the link between ADHD medication and CVD incidence, most studies have focused on short-term effects, averaging a follow-up time of no longer than 2 years. To fill the knowledge gap on long-term effects, investigators studied the cumulative use of ADHD medication and CVD incidence over a 14-year time frame.

“Examining the long-term cardiovascular risk associated with ADHD medication use is clinically important given that individuals with a diagnosis of ADHD, regardless of whether they receive treatment, face an elevated risk of CVD,” study authors said. “Additionally, a substantial proportion of young individuals with ADHD continues to have impairing symptoms in adulthood, necessitating prolonged use of ADHD medication.”

Using nationwide health registers in Sweden to fill the cohort for their nested case-control study, investigators recruited 278,027 individuals with ADHD aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020.

Cases (10,388) were defined as individuals with an incident diagnosis of any CVD, including ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease, during the follow-up period. As many as 5 controls without CVD (51,672), matched on age, sex, and calendar time criteria, were randomly selected for each case.

READ MORE: Heart Attack Linked With Higher Risk of Other Long-Term Health Conditions

The ADHD medications assessed included stimulants (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine) and nonstimulants (atomoxetine, guanfacine).

Compared with no use, investigators found that long-term cumulative use of ADHD medication was associated with an elevated risk of CVD, especially hypertension (adjusted odds ratio [aOR], 1.72; 95% CI, 1.51-1.97 for 3 to ≤5 years and aOR, 1.80; 95% CI, 1.55-2.08 for >5 years) and arterial disease (aOR, 1.65; 95% CI, 1.11-2.45 for 3 to ≤5 years and aOR, 1.49; 95% CI, 0.96-2.32 for >5 years). While hypertension and arterial disease accounted as the primary contributors to the association, no statistically significant link was observed between long-term use of ADHD medication and risk for arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

Notably, investigators observed that for every year that participants used ADHD medication, their risk for CVD increased by 4%. Although a larger risk was observed in a dose-response manner within the first 3 years of cumulative risk, a stable risk persisted over the rest of the 14-year follow up. This effect was observed for both children and adults, as well as females and males.

This risk increased further for those who took a higher average defined daily dose of medication. Among participants with an average defined daily dose exceeding 2 (eg, for methylphenidate >60 mg), each 1-year increase in medication use raised their risk for CVD by 5% (aOR, 1.05; 95% CI, 1.03-1.06).

Investigators also observed a greater risk of CVD associated with stimulant use than with nonstimulant use. Both long-term use of methylphenidate (aOR, 1.20; 95% CI, 1.10-1.31 for 3 to ≤5 years and aOR, 1.19; 95% CI, 1.08-1.31) for >5 years) and lisdexamfetamine (aOR, 1.23; 95% CI, 1.05-1.44 for 2 to ≤3 years and aOR, 1.17; 95% CI, 0.98-1.40 for >3 years) were associated with a prolonged elevated risk of CVD, whereas the aOR for atomoxetine only demonstrated a significant association for the first year of use (aOR, 1.07; 95% CI, 1.01-1.13).

Given the increasing prevalence of ADHD medication use, the current study’s findings hold significant implications for clinical decision-making in ADHD treatment, prompting further evaluation and potential adjustments in treatment approaches.

“These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions on long-term ADHD medication use,” study authors wrote. “Clinicians should be vigilant in monitoring patients, particularly among those receiving higher doses, and consistently assess signs and symptoms of CVD throughout the course of treatment.”

READ MORE: Cardiology Resource Center

References

1. Zhang L, Li L, Andell P, et al. Attention-deficit/hyperactivity disorder medications and long-term risk of cardiovascular diseases. JAMA Psychiatry. 2024;81(2):178-187. doi:10.1001/jamapsychiatry.2023.4294

2. National prevalence of ADHD and treatment: Information on children and adolescents, 2016. News article. CDC. Accessed February 21, 2024. https://www.cdc.gov/ncbddd/adhd/features/national-prevalence-adhd-and-treatment.html