ADHD Meds Linked to Cardiomyopathy in Young Adults

Young adults who are prescribed stimulant medications for attention-deficit/hyperactivity disorder (ADHD) may have a slightly increased risk of cardiomyopathy, according to a retrospective study.

The prevalence of cardiomyopathy after 1 year of taking the drugs was 0.36% in stimulant users and 0.31% in nonusers, Pauline Gerard, MS (University of Colorado School of Medicine, Aurora), a second-year medical student, and colleagues report. The gap continued to widen for use lasting 10 years (0.72% vs 0.53%; P < 0.05 for both)

“The absolute risk in terms of number-needed-to-harm is not large, but the potential consequences are serious and should be acknowledged,” Gerard told TCTMD via email.

“Caution is already recommended in patients with family or personal history of cardiac disease,” she noted, adding that “our results argue that long-term use of stimulant medications should be considered a potential risk factor for dilated cardiomyopathy, even in patients without a known personal or family history of cardiovascular disease.”

Because of the limitations of the retrospective study, however, “these results are not strong enough to indicate that clinicians should avoid prescribing stimulant medications in otherwise clinically indicated situations,” said Gerard, who will present the findings as a poster at the upcoming American College of Cardiology (ACC) 2024 Scientific Session.

Prior studies have established a link between ADHD medications like methylphenidate and amphetamines and cardiovascular issues, including high blood pressure and increased heart rate, as well as a link between abuse of methamphetamines and dilated cardiomyopathy. Research also has shown increased emergency department visits for cardiac complaints in users of prescription stimulants, and even sporadic cases of sudden cardiac death in children. There’s little research into whether the stimulants used for ADHD also are associated with cardiomyopathy risks, however.

“Reviewing the literature ahead of this project showed us that many of the studies looking at safety of stimulant medications mainly looked at the pediatric population and duration of use wasn’t more than 2 to 3 years. So we’re hoping to continue that conversation but with an older population, since many more young adults are taking stimulant medications for ADHD than in previous decades,” Gerard said.

A Starting Point for Further Research

To explore the issue, the investigators turned to the TriNetX database, which contains information from about 80 US hospitals. The analysis included 12,759 adults ages 20 to 40 who had a diagnosis of ADHD and were prescribed stimulants, matching them with an equal number of peers with ADHD who were not prescribed stimulants.

Based on ICD-10 codes reflecting cardiomyopathy potentially linked to stimulant use, those who were prescribed the medications had increased odds of cardiomyopathy after 1 year of use (OR 1.17; 95% CI 1.06-1.30) and 10 years of use (OR 1.37; 95% CI 1.002-1.88).

“Ideally, this study would serve as a starting point for further research by highlighting that there is an increased risk of cardiomyopathy with long-term stimulant use in young adults,” Gerard said.

As for what might explain the higher risk of cardiomyopathy associated with amphetamine use in ADHD, she said the most frequently proposed mechanisms “include increased oxidative stress due to higher levels of circulating catecholamines, perfusion defects, altered cardiac gene expression and, in turn, abnormal cardiac protein synthesis, to name a few.”

Maya Guglin, MD, PhD (Indiana University Health, Indianapolis), chair of the ACC’s heart failure and transplant council, who was not involved in the study, said the findings are not particularly unexpected based on what’s known about people who abuse methamphetamines, who can develop cardiomyopathy related to their drug use.

Methamphetamine activates catecholamines—which induce vasoconstriction, hypertension, and tachycardia—and it also has direct toxic effects on the heart. “All of this, in some individuals, produces cardiomyopathy,” Guglin said, noting that similar mechanisms are likely at play among individuals taking stimulants over the long term for ADHD.

Regarding the magnitude of the risk observed in the current cohort, she said it’s small, but added that cardiomyopathy is not a minor problem. “Although the risk is small, I would not dismiss it as unsubstantial. I think it is a serious issue they raised,” Guglin said. “I would keep it in mind because it is not a minor disease. It is not some nuisance. It really interferes with your life, both quality and longevity.”

Gerard said further research is needed to determine how much overlap there is between the mechanisms underlying cardiomyopathy tied to use of methamphetamines versus amphetamines before coming to any definitive conclusions about the relationships observed here.

“The main takeaway is that it is important for clinicians to be aware that long-term stimulant use could lead to an increased risk of dilated cardiomyopathy. However, there just isn’t enough data out there to confirm or deny that stimulant medication use can cause heart failure in the absence of other risk factors,” she said.

Moving forward, Gerard added, “given the surge in stimulant prescriptions during the COVID-19 pandemic and the overall increase in use of these medications as we deepen our understanding of the pathophysiology of ADHD, studying the effects of these medications in an older population and with a longer duration of use than has been evaluated so far would help us safeguard patients’ long-term health.”