Published in Communications Medicine, the study analyzed nearly 20 years of electronic health records from more than 650,000 adults in the United States diagnosed with IBS. This makes it the largest real-world investigation to date focused on how safe these treatments are over extended periods.

Understanding IBS and Its Treatment Options

IBS is a chronic digestive disorder that affects roughly 10% of people in the U.S. While there is no cure, symptoms can often be managed through dietary changes, behavioral therapies and medications.

“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.”

Study Finds Elevated Risks With Certain IBS Medications

The research team examined patients using a range of treatments, including Food and Drug Administration-approved IBS drugs, antidepressants, antispasmodics and opioid-based antidiarrheal medications such as loperamide and diphenoxylate, which are commonly recommended for symptom relief.

Their analysis found that long-term use of antidepressants was associated with a 35% increase in the risk of death. Use of loperamide and diphenoxylate was linked to about twice the risk of death compared to those not taking these medications.

What the Findings Do and Do Not Show

Importantly, the study does not prove that these medications directly cause death. Instead, the associations may reflect a higher likelihood of serious health complications among those taking them, including cardiovascular events, falls and stroke.

Although antidepressants are not FDA-approved specifically for IBS, they are often prescribed to help manage pain and reduce symptom severity. The researchers noted that other commonly recommended treatments, including FDA-approved IBS medications and antispasmodics, were not associated with an increased risk of death.

Small Individual Risk but Important Considerations

The researchers stressed that while the increased risks are statistically meaningful, the overall risk for any one patient remains low.

“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.”

Call for More Research and Personalized Care

Rezaie emphasized that additional studies are needed to confirm these findings and determine which patients might be most vulnerable. He also highlighted the need for future treatment guidelines to better address the long-term safety of medications frequently used for IBS.

In the meantime, he encouraged a more individualized approach to 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.

Additional Cedars-Sinai authors include Sepideh Mehravar, MD, Yee Hui Yeo, MD, and Mark Pimentel, MD.

Other authors include Parnian Naji, MD, Wee Han Ng, Nils Burger, PhD, and Will Takakura, MD.

Conflicts of Interest: Mark Pimentel is also a consultant for and received grant support from Bausch Health. Ali Rezaie reports serving as a consultant for Bausch Health and Ardelyx. In addition, Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech. Ali Rezaie and Mark Pimentel have equity in Gemelli Biotech and Good LFE. The remaining authors disclose no conflicts.