Long-Term Antidepressant Use Linked to Higher Risk of Sudden Cardiac Death: Study

Sudden cardiac death (SCD) refers to the unexpected death of a person, typically due to a heart-related issue, occurring within one hour of symptom onset in witnessed cases or within 24 hours of the person being last seen alive in unwitnessed cases.

In younger individuals under 39, it is often caused by thickening of the heart muscle or electrical abnormalities, whereas in older individuals, it is more commonly linked to narrowing of the heart’s blood vessels.

The study presented at EHRA 2025, a scientific congress of the European Society of Cardiology, has found that individuals with a history of antidepressant use face an increased risk of sudden cardiac death compared to those with no history of antidepressant exposure.

The study analysed all deaths in Denmark among residents aged 18-90 years in 2010, categorizing them as non-SCD or SCD based on death certificates and autopsy reports. Antidepressant exposure was defined as redeeming a prescription at least twice in one year over a 12-year period before follow-up.

The findings revealed that among 4.3 million residents, there were 45,701 total deaths, including 6,002 cases of SCD. A total of 643,999 individuals had prior antidepressant exposure, with 1,981 SCD cases occurring in this group, compared to 4,021 in the unexposed population.

After adjusting for age, sex, and comorbidities, the study found that individuals exposed to antidepressants for 1-5 years had a 56% higher risk of sudden cardiac death, while those exposed for six or more years faced a 2.2 times higher risk.

The impact was particularly pronounced in younger individuals; those aged 30-39 with 1-5 years of exposure were three times more likely to suffer SCD, and this risk increased to five times for those with six or more years of exposure.

In the 50-59 age group, the risk doubled for those with shorter exposure and quadrupled for those with longer exposure. The risk associated with prolonged antidepressant use decreased in older individuals, with those aged 70-79 experiencing a 1.83 times increased risk for 1-5 years of exposure and a 2.2 times increased risk for six or more years.

Among individuals aged 40-79, the SCD incidence rate ratio was significantly higher in those with six or more years of exposure compared to those with 1-5 years, with the highest relative increase observed in the 50-59 age group, where the risk doubled. However, for those under 39 or over 80, the difference in risk between short- and long-term exposure was not statistically significant.

“Exposure time to antidepressants was associated with a higher risk of sudden cardiac death, and linked to how long the person had been exposed to antidepressants,” says study co-author Dr Jasmin Mujkanovic, Rigshospitalet Hjertecentret, Copenhagen, Denmark. “Those exposed for six years or more were at even more increased risk than those exposed for 1 to 5 years, when compared with people unexposed to antidepressants in the general population.”

On the potential reasons for the association, he adds: “The increased risk of sudden cardiac death may be attributed to the potential adverse effects of the antidepressants. However, the exposure time to antidepressants might also serve as a marker for more severe underlying illness. Additionally, the increase could be influenced by behavioural or lifestyle factors associated with depression, such as delayed healthcare seeking and poor cardiovascular health. Further research is warranted.”