The use of antidepressant (AD) medications has been linked to a substantial increase in the risk of sudden cardiac death (SCD), as per research presented at the recent European Heart Rhythm Association (EHRA) congress (30 March–1 April 2025, Vienna, Austria).
According to a European Society of Cardiology (ESC) press release, causes of SCD in people under the age of 39 years are often a thickening of the heart muscle or an electrical problem with the heart—while, in older people, SCD is more likely to be caused by a narrowing of the blood vessels that supply the heart.
Previous research has indicated that patients with psychiatric disorders have an increased all-cause mortality risk as well as double the risk of SCD across all age groups, but the impact of AD exposure on SCD risk has “so far been unclear”, the release adds.
At EHRA 2025, researchers presented data showing that—compared to the general population with no history of AD use—individuals with a history of AD use have an increased risk of SCD, which varies based on age and time of exposure.
“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,” said study co-author Jasmin Mujkanovic (Rigshospitalet Hjertecentret, Copenhagen, Denmark). “Those exposed for six years or more were at even more increased risk than those exposed for 1–5 years, when compared with people unexposed to antidepressants in the general population.”
The authors examined all deaths in Denmark among residents aged 18–90 years by reviewing all death certificates and autopsy reports from 2010. Deaths were categorised as non-SCD or SCD based on the available information, while exposure to ADs 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, patients were divided into two groups based on exposure time: 1–5 years, and six or more years.
Among 4.3 million residents, there was a total of 45,701 deaths and 6,002 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 SCDs in the AD cohort and 4,021 in the unexposed general population.
The researchers ultimately found that the incidence rate ratio of SCD was significantly higher in the medication-exposed groups compared to the general population across all age groups—except for the group aged 18–29 years, for whom the association was not statistically significant.
When the data were adjusted for age, sex and comorbidities, compared with the unexposed general population, the group exposed to ADs for 1–5 years had a 56% higher risk of SCD, while those exposed to ADs for six or more years experienced a 2.2-times higher risk.
In individuals aged 30–39 years, those with 1–5 years of AD exposure were around three times more likely to suffer SCD versus the unexposed general population—a risk that 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 ADs for 1–5 years saw their risk of SCD doubled, while individuals exposed to ADs for six or more years had four times the risk of SCD.
However, the differences in risk associated with varying periods of AD exposure decreased in older groups. In people aged 70–79 years compared to the unexposed general population, those with 1–5 years of AD exposure had a 1.83-times increased risk, whereas those with six 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 people with six or more years of exposure to AD compared to persons with 1–5 years of exposure. Additionally, the increased risk differed for each 10-year age group, such that—for those aged 40–49 years—the risk of SCD increased by 70% for those with six 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 those aged 39 years and under versus 80 years and over, the difference in increased risk between six years and 1–5 years of AD exposure was not statistically significant.
“The increased risk of sudden cardiac death may be attributed to the potential adverse effects of the antidepressants,” Mujkanovic commented. “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.”
