Long-term use of antidepressants linked to sudden cardiac death

New research presented at EHRA 2025 has shown that patients who have taken antidepressants for extended periods are at increased risk of sudden cardiac death.

Compared to the general population with no history of antidepressant use, the risk was higher for patients with 1–5 years of exposure (hazard ratio [HR], 1.56) and those with ≥6 years of use (HR, 2.17) after adjusting for age, sex, and comorbidities. Additionally, longer exposure to antidepressants was associated with a heightened risk among individuals aged 40–79 years, with the greatest impact among people in their 50s. [Mujkanovic J, et al, EHRA 2025]

“We know that it is more dangerous to be exposed compared to the general population, but it appears that it also has an impact if you’re exposed for a longer time,” said presenting author Dr Jasmin Mujkanovic from Rigshospitalet-Copenhagen University Hospital, Denmark.

The missing link

The researchers had shown in a previous study that the rate of sudden cardiac death is higher in patients with psychiatric disorders, including those with depressive disorders, across all age groups than in the general population. However, the impact of antidepressant use remained unclear. [Heart 2024;110:1365-1371]

To explore the association further, they examined death certificates and autopsy reports of Danish individuals aged 18–90 from 2010. They identified those who had filled at least two prescriptions for antidepressants for 1 year over the past 12 years.

Among 4.3 million people with complete data, there were 45,701 deaths and 6,002 cases of sudden cardiac deaths. Approximately 643,999 people had a history of exposure to antidepressants, and there were 1,981 sudden cardiac deaths in the antidepressant cohort and 4,021 in the unexposed general population.

The incidence rate of sudden cardiac death was significantly higher among patients who had taken antidepressants, regardless of duration, than among those unexposed across all age groups, except for patients aged 18–29 years.

When asked how he accounted for the impact of psychological disorders in his analysis, Mujkanovic said: “Of course, if you have a severe depression, you will be more exposed [to antidepressants]. Honestly, it is difficult to assess whether it is the medication or the depression itself.”

Clinical implications

Dr Elena Arbelo from Hospital Clínic de Barcelona, Spain, commented that this type of observational study is useful for generating hypotheses but cannot help to answer questions about the mechanism. However, she said physicians may be able to use the results to help manage their patients.

“When you start a patient on antidepressants, first you could rule out the presence of major cardiomyopathies or electrical diseases,” she suggested. “It’s not scientifically based, but we know that patients who are prone to QTc prolongations have a higher risk of cardiac arrest.”

Clinicians should also consider monitoring patients’ ECG for potential arrhythmias after initiating antidepressants as part of a prospective registry, she added.

Additionally, Arbelo said the findings should help raise awareness about the relationship between antidepressant use and cardiac death risk and are not meant to scare patients.

“It is likely that the antidepressant use is just a marker of an underlying problem that led to the antidepressants — a risk marker rather than a factor itself predisposing to sudden cardiac death,” she explained.  Additionally, she said the increase could be influenced by behavioural or lifestyle factors associated with depression, such as delayed healthcare seeking, and poor cardiovascular health. “That’s why we need more data moving forward.”