April 02, 2025 Preliminary results from a new study showed that the risk for sudden cardiac death (SCD) was more than twice as high in individuals who used antidepressants for 6 or more years compared with that in those not taking the medications. While the findings suggest a possible association between long-term antidepressant use and SCD, researchers caution that the results do not imply these medications are inherently dangerous or should be discontinued. “I hope doctors don't think they need to discontinue this treatment because it might pose a risk of sudden cardiac death,” study investigator Jasmin Mujkanovic, MD, PhD student, Copenhagen University Hospital, Copenhagen, Denmark, told Medscape Medical News. Mujkanovic emphasized that depression itself is a known risk factor for SCD and that effective treatment can improve quality of life and support healthier lifestyle choices, which may in turn help reduce heart-related risks. The findings were presented on March 30 at the European Heart Rhythm Association 2025, a scientific congress of the European Society of Cardiology. Previous research has shown a link between long-term antidepressant use and poor cardiac health. Antipsychotics have also been tied to an increase risk for cardiovascular disease in older adults with dementia. While earlier studies suggested that patients with depressive disorders have an increased risk for SCD, the effect of antidepressant exposure on SCD risk was unclear. Researchers reviewed all death certificates and autopsy reports from 2010 among the 4.3 million residents of Denmark aged 18-90 years. The year 2010 was chosen because some of Mujkanovic's colleagues had already assessed every death certificate for that year and entered pertinent information into a database. The researchers defined antidepressant exposure as having filled at least two prescriptions for the medication within a single year during the 12 years leading up to 2010, the start of the follow-up period. Exposure was categorized as either 1-5 years or 6 years or more. Based on available data, deaths were categorized as SCD or non-SCD. There were 6002 deaths due to SCD, which included 1981 in the antidepressant cohort and 4021 in the unexposed population. Investigators found that the risk for SCD was significantly higher in individuals exposed to antidepressants than in the general population across all age groups — except those aged 18-29 years, where the association was not statistically significant. Mujkanovic suggested that younger patients may not have used antidepressants long enough to be classified as having prolonged exposure. After adjusting for age, sex, and comorbidities, including ischemic heart disease, chronic obstructive pulmonary disease, diabetes and arrhythmias, the risk for SCD was 56% higher in those with 1-5 years of exposure to antidepressants (hazard ratio [HR], 1.56; P < .001) and more than double for those with 6 or more years of exposure (HR, 2.17; P < .001). The risk for SCD among individuals taking antidepressants, compared with the unexposed general population, varied slightly across age groups. However, among those aged 40-79 years, the incidence of SCD was significantly higher in individuals with 6 or more years of antidepressant use than in those with 1-5 years of exposure. When comparing longer to shorter durations of antidepressant use, the differences in risk were significant in the following age groups: 40-49 years (incidence rate ratio [IRR], 1.7; P = .03), 50-59 years (IRR, 2.0; P < .001), and 60-69 years (IRR, 1.4; P < .001). The differences in risk between antidepressant exposure durations were not statistically significant among the younger participants (age, 18-39 years) and the oldest group (age, 80-90 years). Due to the study's design, it's challenging to determine whether the increased risk for SCD is linked to the underlying condition of depression or to the antidepressant medications themselves, Mujkanovic said. However, if the medications do contribute to the risk, it may be because some can alter the heart's electrical activity, he noted. Mujkanovic also pointed out that certain antidepressants are associated with significant weight gain and QT interval prolongation, which can lead to metabolic syndrome — a known risk factor for atherosclerosis. “It's like a chain reaction — atherosclerosis is a known risk factor for ischemic heart disease, and ischemic heart disease increases the risk for myocardial infarction, which increases the risks for cardiac death,” Mujkanovic said. The study did not distinguish between different classes of antidepressants — such as selective serotonin reuptake inhibitors and tricyclics — and participants may have switched between classes during the study period. It also did not analyze men and women separately, though Mujkanovic expressed interest in exploring sex-specific differences in future research. Several experts weighed in on the findings in a statement from the UK-based independent nonprofit Science Media Centre (SMC). Paul Keedwell, MB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists in London, the United Kingdom, agreed with the investigators' caution against discontinuing antidepressants based on the study's findings. “The results should be treated with caution because the study was unable to separate the risks of antidepressant treatment from the risk of having depression per se,” Keedwell said. Depression is linked to a 60% higher risk for heart disease, including SCD, a 50%-90% increased risk for life-threatening arrhythmias, and approximately double the risk for heart attack, Keedwell noted. He added that individuals with depression tend to die earlier than those in the general population — with men dying up to 14 years earlier and women dying up to 10 years earlier. While suicide contributes to this excess mortality, Keedwell emphasized that the leading cause is poor physical health, likely driven by an unhealthy lifestyle. “More research is needed to directly compare the life expectancy in treated and untreated depression, but as things stand, the weight of evidence supports the conclusion that the risk of early death is much higher when depression is left untreated than when it is treated,” he said. “Therefore, people should not stop their antidepressant treatment based on this study.” Also commenting for the SMC, Charles Pearman, MB, PhD, consultant cardiologist and electrophysiologist at Manchester University NHS Foundation Trust, noted that previous studies have identified a link between antipsychotic use and an increased risk for SCD. He added that antidepressants may not directly cause SCD but could instead serve as markers for other underlying health issues or risk factors — such as obesity, hypertension, diabetes, smoking, or physical inactivity. “The investigators tried to account for this possibility, but it is unclear which risk factors they considered,” Pearman said. Pearman emphasized that the overall risk remains low and, like the study authors, advised against patients abruptly discontinuing their antidepressant treatment. Overall, while there was an increased risk from taking antidepressants, the risk remains small, he noted. “People who are concerned about their risks should speak to their GP [general practitioner] rather than stopping their medicines abruptly,” he said. The study received no external funding. Mujkanovic and Keedwell reported n o related conflicts of interest. Pearman disclosed no relevant conflicts. Send comments and news tips to news@medscape.net.