Common antidepressants may accelerate heart valve disease in some patients
A multicenter study has found that widely prescribed SSRI antidepressants may accelerate severe heart valve degeneration in patients with a specific genetic variant, a finding that could reshape prescribing practices and surgical planning across Europe's public health systems.
Researchers led by Columbia University have found that patients taking selective serotonin reuptake inhibitors (SSRIs) like Prozac and Zoloft are more likely to need mitral valve surgery at a younger age if they suffer from degenerative mitral regurgitation (DMR).
DMR is one of the most common forms of heart valve disease. As the valve's thin flaps degenerate, blood leaks backward into the heart, forcing the organ to work harder and potentially leading to atrial fibrillation or heart failure. Medicines can only ease symptoms, meaning severe cases ultimately require surgical repair or replacement.
Published in Science Translational Medicine, the multicenter investigation included researchers from the Children's Hospital of Philadelphia, the University of Pennsylvania, and the Valley Hospital Heart Institute. The team reviewed data from over 9,000 patients alongside 100 tissue biopsies. With SSRIs ranking among the most widely prescribed antidepressants in Europe, these findings carry significant implications for public health systems strained by the high costs of cardiac surgery and chronic disease management.
The scientists discovered that reduced activity of the serotonin transporter (SERT) accelerates structural damage in valves that are already degenerating. SSRIs work by reducing SERT activity to keep serotonin in the brain longer, but this mechanism appears to inadvertently affect heart tissue.
A genetic variant in the SERT gene, known as the "long-long" variant, makes certain patients particularly vulnerable. Laboratory tests showed that valve cells from patients with this variant produced excess collagen when exposed to fluoxetine, making the valve thicker, stiffer, and more prone to leakage.
"Studying the data of these patients, we found that taking SSRIs was associated with severe mitral regurgitation that needed to be treated with surgery at a younger age than for patients not taking SSRIs," said Giovanni Ferrari, the study's co-lead and scientific director of the Cardiothoracic Research Program at Columbia.
The researchers propose a simple DNA test using a blood sample or mouth swab to identify patients with low SERT activity. Identifying high-risk patients early could allow health systems to prioritize surgical intervention before expensive complications like congestive heart failure arise.
"Assessing patients with DMR for low SERT activity may help identify patients who may need mitral valve surgery earlier," Ferrari said. "Promptly fixing a mitral valve that is very leaky would protect the heart and could prevent congestive heart failure."
Crucially, the researchers found no harmful effects in healthy human mitral valves. "SSRIs are generally safe for most patients," Ferrari noted, emphasizing that the risk applies only once a valve has already started to degenerate. The findings do not justify patients stopping their medication without consulting a doctor.
