Longer Use of ADHD Medications Linked to Higher Risk of CVD in Recent Study

Long-term use of attention deficit-hyperactivity disorder (ADHD) medications was associated with an increased risk of cardiovascular disease (CVD), particularly hypertension (HTN) and arterial disease, according to a nested case-control study led by researchers from the Karolinska Institute in Sweden.¹

The risk of CVD increased with longer cumulative exposure to ADHD medications, peaking at 3 to 5 years of use (adjusted odds ratio [AOR] 1.27, 95% CI 1.17-1.39), reported lead author Zheng Change, PhD, senior researcher, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Solna, Sweden, and colleagues in JAMA Psychiatry.¹

When researchers examined the association between ADHD medication use and specific CVDs, results showed that longer cumulative ADHD medication use was associated with an increased risk of HTN (3 to ≤5 years: AOR 1.72, 95% CI 1.51-1.97; >5 years: AOR 1.80, 95% CI 1.55-2.08) and arterial disease (3 to ≤5 years: AOR 1.65, 95% CI 1.11-2.45; >5 years: AOR 1.49, 95% CI 0.96-2.32).¹

“There is a long list of drugs that have been linked to a comparable increased risk of hypertension when used long-term such as the one found here, so patients should not be alarmed by these findings,” said first author Le Zhang, PhD, postdoctoral researcher, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, in a press release. “However, in clinical practice, the raised risk should be carefully weighed against the recognised benefits of treatment on a case-by-case basis. Doctors should also regularly follow up the ADHD patients to find signs and symptoms of cardiovascular disease while they’re on medication over the long-term.”²

As the use of ADHD medications has increased during the past decades, concerns about their cardiovascular side effects have also risen. Meta-analyses of randomized controlled trials have reported increases in heart rate and blood pressure for both stimulant and nonstimulant ADHD medications.¹

Findings from longitudinal observational studies have been mixed, noted investigators. “A meta-analysis of observational studies found no statistically significant association between ADHD medication and risk of CVD. However, the possibility of a modest risk increase cannot be ruled out due to several methodological limitations in these studies,” they wrote.¹

The authors stress the lack of research on the long-term CV risks associated with ADHD medications, a particularly important gap given that children diagnosed with the disorder continue to have symptoms into adulthood, prolonging exposure to the drugs, they wrote. In addition, they cite research showing a trend toward long-term use, “with approximately half of individuals using ADHD medications for over 5 years.”¹

To assess the association between cumulative use of ADHD medication and the risk of CVD up to 14 years, Zhang and coauthors used Sweden’s nationwide health registers to assess data on 258 835 persons aged 6-64 years with an incident diagnosis of ADHD or ADHD medication dispensation from 2007 to 2020. The primary outcome was incident CVD, such as ischemic heart disease, cerebrovascular diseases, HTN, heart failure, arrhythmias, thromboembolic disease, and arterial disease.¹

Among the cohort, 10 388 individuals had a diagnosis of CVD and were included in the final assessment and matched with 51 672 control participants. Among both groups, the median age was 34.6 years, 59.2% were men, and were followed for a median of 4.1 years.¹

Results showed that across the 14-year follow-up period, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR 1.04, 95% CI 1.03-1.05), with a larger increase in risk in the first 3 years of cumulative use (AOR 1.08, 95% CI 1.04-1.11) and stable risk over the remaining follow-up. Investigators noted similar results were observed in children and youth (aged <25 years) and adults (aged ≥25 years).¹

When researchers analyzed specific ADHD medications, they found that long-term use of methylphenidate was associated with an increased risk of CVD compared with no use (3 to ≤5 years: AOR 1.20, 95% CI 1.10-1.31; and >5 years: AOR 1.19, 95% CI 1.08-1.31). Lisdexamfetamine was also associated with an elevated risk of CVD (2 to ≤3 years: AOR 1.23, 95% CI 1.05-1.44; and >3 years: AOR 1.17, 95% CI 0.98-1.40).¹

“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,” concluded Zhang et al. “Monitoring becomes even more crucial considering the increasing number of individuals engaging in long-term use of ADHD medication.”¹

References:

1. Zhang L, Li L, Andell P. Attention-deficit/hyperactivity disorder medications and long-term risk of cardiovascular diseases. JAMA Psychiatry. Published online November 22, 2023. doi:10.1001/jamapsychiatry.2023.4294

2. New findings on long-term treatment of ADHD and link to cardiovascular disease. News release. Karolinska Institute. November 28, 2023. Accessed December 1, 2023. https://news.ki.se/new-findings-on-long-term-treatment-of-adhd-and-link-to-cardiovascular-disease