Long-Term SSRI Use May Increase Risk of Sudden Cardiac Death

Researchers warn that the longer patients used SSRIs like Lexapro and tricyclic antidepressants, the greater risk they face of experiencing fatal cardiac problems.

New research links the use of antidepressants like Lexapro and Zoloft to potentially deadly heart problems, with those risks increasing the longer a person takes the popular depression treatments.

According to findings published in the journal Heart Rhythm on March 11, using selective serotonin reuptake inhibitors (SSRIs) for five years or less increased the risk of sudden cardiac death by more than 40%. For those taking the drugs longer than six years, the hazard ratio increased to more than 70% higher than patients not taking the drugs.

SSRIs are a class of antidepressants used to treat depression, anxiety and other mental health conditions. They are considered a first-line treatment for depression and are the most commonly prescribed antidepressant.

The medications work by increasing serotonin levels in the brain. At the same time, the antidepressants prevent reabsorption of that same neurotransmitter to help prevent depression. Common SSRIs include Prozac, Zoloft, Lexapro and Paxil.

Prior research has linked SSRI use to an increased risk of suffering brain bleeds after a person has a stroke, an increased risk of developing severe dementia and may increase the risk of children developing Type 2 diabetes.

Additionally, a 2021 Danish study indicated pregnant women taking antidepressants like Zoloft and Paxil increase the risk their children would suffer learning disabilities. Children born to moms who took SSRIs scored lower on math and other standardized testing.

For the new study, researchers from Copenhagen University Hospital in Denmark conducted a nationwide study of 4.3 million Danish residents ages 18 to 90 years old. Led by Dr. Jasmin Mujkanovic, the team also analyzed the national prescription registry from 1999 to 2009.

Antidepressant use was considered as two or more prescriptions within one calendar year for 1 through 5 years, compared with 6 or more years of use.

More than 6,000 sudden cardiac deaths occurred during the study period. Sudden cardiac death is any unexpected death caused by cardiac arrest, or loss of heart function. Roughly 75% of cases involve underlying coronary artery disease.

Among sudden cardiac death patients, one-third of them used antidepressants, the researchers discovered. The data also indicated people who used SSRIs for 1 through 5 years had a 41% increased risk of suffering sudden cardiac death. Those who used SSRIs like Zoloft for 6 or more years had a 74% increased risk of suffering sudden cardiac death.

Similarly, the risk of sudden cardiac death for tricyclic antidepressants, including medications like Elavil and Vanatrip, was also elevated, though not as high as those linked with SSRI use. Patients taking tricyclic antidepressants had a 24% higher risk of cardiac death after one to five years of use, which increased to 40% among those who used the medications for more than six years.

“While causality cannot be inferred, these findings identify patients receiving prolonged antidepressant therapy as a population at elevated cardiovascular risk warranting further investigation.”

— Dr. Jasmin Mujkanovic, Antidepressant treatment duration and risk of Sudden Cardiac Death: A Nationwide Cohort Study

Researchers called on doctors to always discuss the benefits and the risks of taking antidepressants with their patients.

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