Sudden Cardiac Death Risk Linked to Long-term Antidepressant Use

VIENNA, Austria—Patients who have been taking antidepressants for longer periods of time are at a significantly increased risk of sudden cardiac death, according to new research out of Denmark.

Compared with the general population, risk was higher both for those with 1 to 5 years of exposure (HR 1.56; 95% CI 1.46-1.67) and those with 6 or more years of use (HR 2.17; 95% CI 2.01-2.31) after adjustment for age sex, and comorbidities. Moreover, longer versus shorter exposure to antidepressants was associated with a heightened risk among people ages 40 to 79 years.

“We know that it is more dangerous to be exposed when compared to the general population, but it appears it’s also an impact if you’re exposed for a longer time,” said Jasmin Mujkanovic, MD (Rigshospitalet - Copenhagen University Hospital, Denmark), who reported the findings here at the European Heart Rhythm Association Congress 2025.

The researchers had previously shown that patients with psychiatric conditions, including those with depressive disorders, have about double the risk of sudden cardiac death compared with people in the general population, but the impact of antidepressant medication use had been unclear.

To explore that issue, they examined death certificates and autopsy reports for all Danish individuals ages 18 to 90 who died in 2010 and identified those who had filled at least two prescriptions for antidepressants during a single year over the preceding 12-year period.

Among the roughly 4.3 million people living in Denmark in 2010, there were 45,701 deaths, including 6,002 categorized as sudden cardiac deaths. In addition, 643,999 residents had a history of exposure to antidepressants, and there were 1,981 sudden cardiac deaths in this group.

The incidence rate of sudden cardiac death was significantly higher among patients taking antidepressants—for any duration—than among individuals who were unexposed across all age groups, except for the youngest (18 to 29 years).

A significantly greater risk seen with antidepressant use for 6-plus versus 1 to 5 years, however, was observed only for age groups spanning 40 to 79 years, with the greatest impact for people in their 50s.

Sudden Cardiac Death Risk With Antidepressant Use 6+ vs 1-5 Years

During a discussion following his presentation, Mujkanovic was asked how he accounted for the influence of psychological disorders like depression in his analysis. “I don’t think you can, is the short answer,” he replied. “Obviously, if you have a severe depression, you will be more exposed [to antidepressants]. So it’s difficult to assess whether it’s the medication or it’s the depression itself.”

Indeed, commented European Society of Cardiology spokesperson Elena Arbelo, MD, PhD (Hospital Clínic de Barcelona, Spain), this type of observational study is useful for generating hypotheses but cannot be used to answer questions about mechanism. “Now we have to do a deep dive into why this may have happened,” she said.

In the meantime, however, physicians may be able to use this information to help manage their patients. For instance, “when you start a patient on antidepressants, first you could rule out the presence of major cardiomyopathies or electrical diseases,” Arbelo suggested. “It’s not scientifically based, but we know that patients who are prone to QTc prolongations have a higher risk of cardiac arrest.”

It’s likely that the antidepressant use is just a marker of an underlying problem that led to the antidepressants. Elena Arbelo

Clinicians could also consider monitoring their patients with ECGs for the development of arrhythmias after they start taking antidepressants, perhaps as part of a prospective registry, she said.

At this point, Arbelo said, the findings of this study should serve to raise awareness that there is a relationship between antidepressant use and risk of sudden cardiac death and should not be used to cause concern among patients.

“In this type of study, it’s likely that the antidepressant use is just a marker of an underlying problem that led to the antidepressants—so it’s a risk marker rather than a factor itself predisposing to sudden cardiac death,” she said, adding, “We need more data for sure.”