Antidepressant use associated with higher risk of sudden cardiac death in all age groups

Sudden cardiac death (SCD) refers to an unexpected death of a person, believed to be caused by a heart-related issue. It occurs within one hour of the onset of symptoms in witnessed cases or within 24 hours of the person being last seen alive in unwitnessed cases. 

The causes in people under the age of 39 are often a thickening of the heart muscle or an electrical problem with the heart. In older people, SCD is more likely to be caused by a narrowing of the blood vessels that supply the heart. 

Previous research has shown1 that patients with psychiatric disorders have an increased all-cause mortality as well as double the risk of sudden cardiac death across all age groups. However, the impact of antidepressant exposure on SCD risk has so far been unclear. 

In new research presented at EHRA 2025, a scientific congress of the European Society of Cardiology, researchers show that, compared with the general population with no history of antidepressant (AD) use, individuals with a history of AD use have an increased risk of SCD, which varies based on age and time of exposure. 

The authors examined all deaths in Denmark among residents aged 18-90 years in 2010 by reviewing all death certificates and autopsy reports. Deaths were categorized as non-SCD or SCD based on the available information. Exposure to AD was defined by redemption of a prescription for AD medication at least twice in one year over a period of 12 years before the year of follow-up (2010). Furthermore, exposure time was divided into two groups: 1 to 5 years and 6 or more years. 

Among the 4.3 million residents in 2010 aged 18-90 years, there were a total of 45,701 deaths and 6002 cases of SCD. A total of 643,999 inhabitants were exposed to AD medication prior to the year of follow-up. There were 1,981 sudden cardiac deaths in the AD cohort and 4,021 in the unexposed general population. The incidence rate ratio of SCD was significantly higher in the exposed groups compared to the general population across all age groups except for the age group 18-29 years, for whom the association was not statistically significant (see table 1, annex). 

When the data was adjusted for age, sex and comorbidities, compared with the unexposed general population, the group exposed to antidepressants for 1 to 5 years had a 56% higher risk of sudden cardiac death, while those exposed to antidepressants for six or more years experienced a 2.2 times higher risk. 

In individuals aged 30-39 years, compared with the unexposed general population, those with 1 to 5 years of antidepressant exposure were around three times more likely to suffer sudden cardiac death. This risk increased to five times higher for those with six or more years of AD exposure. 

In individuals aged 50-59 years, compared with the unexposed general population, those exposed to antidepressants for 1 to 5 years saw their risk of sudden cardiac death doubled, while individuals exposed to antidepressants for 6 or more years had four times the risk of sudden cardiac death. 

The differences in risk associated with varying periods of antidepressant exposure decreased in older groups. In individuals aged 70-79 years compared to the unexposed general population, those with 1-5 years AD exposure had a 1.83 or 83% times increased risk, whereas those with 6 years or more exposure had a 2.2 times increased risk of SCD. 

In individuals aged 40-79 years, the SCD incidence rate ratio was significantly higher among persons with 6 or more years of exposure to AD compared to persons with 1-5 years of exposure (see table 2, annex). The increased risk differed for each ten-year age group, so that for those aged 40 to 49 years, the risk of SCD increased by 70% for those with 6 or more years of exposure compared to 1-5 years of exposure, and the corresponding increases for 50-59 years, 60-69 years, and 70-79 years were 100%, 40% and 20%, respectively. For persons aged 39 years and under and 80 years and over, the difference in increased risk between 6 years and 1-5 years of AD 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. Those exposed for 6 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." 

Dr. Jasmin Mujkanovic, Rigshospitalet Hjertecentret, Copenhagen, Denmark

On the potential reasons for the association, she 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."