Review Investigates the Long-Term Risks of IBS Medications

A large, long-term study led by Cedars-Sinai Health Sciences University investigators suggests that some medications commonly prescribed to treat irritable bowel syndrome (IBS)-including antidepressants-may be associated with a small but measurable increase in the risk of death.

The findings, published in Communications Medicine, are based on nearly two decades of electronic health records from more than 650,000 U.S. adults with IBS, making it the largest real-world study to examine the long-term safety of IBS treatments.

IBS is a chronic gastrointestinal condition affecting about 10% of the U.S. population. There is no cure, but dietary modifications, behavioral therapy and medications can help manage symptoms.

“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai and senior author of the study. “However, most clinical trials of these medications last less than a year, so we know very little about their long-term safety. This study begins to address that gap.”

Researchers assessed patients taking Food and Drug Administration-approved IBS medications, as well as antidepressants, antispasmodics and opioid-based antidiarrheal drugs, such as loperamide and diphenoxylate-widely used and recommended in IBS care. They found that long-term antidepressant use was associated with a 35% higher risk of death, and that loperamide and diphenoxylate use were associated with roughly double the risk of death.

The study does not establish that these medications directly cause death; rather, the observed associations may reflect higher rates of adverse outcomes, such as cardiovascular events, falls and stroke, which were more frequent among exposed patients.

Although antidepressants are not FDA-approved for IBS, they are commonly prescribed for IBS patients to help reduce pain, calm symptoms and make the condition easier to manage. The study found that other recommended treatments, including FDA-approved medications and antispasmodics, were not associated with increased mortality risk.

Researchers emphasized that while the increase in risk is significant and may sound concerning, the overall risk to any individual patient is small.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Rezaie, the director of Bioinformatics at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai. “Patients should speak with their healthcare provider about the safest and most effective options for managing their symptoms.”

Rezaie said more research is needed to confirm these findings and identify which patients may be at greatest risk. He also called for future treatment guidelines to better address the long-term safety of medications commonly used to manage IBS.

In the meantime, he emphasized a more personalized approach to IBS patient care.

“Treatment for IBS patients should focus on identifying the underlying causes and using the safest, evidence-based options available rather than relying on a single class of medications for long-term management,” Rezaie said.