A massive long-term study tracking more than 650,000 Americans with irritable bowel syndrome is raising new concerns about the safety of some commonly used treatments.
A major long-term study led by researchers at Cedars-Sinai Health Sciences University is shedding new light on the safety of medications commonly used to treat irritable bowel syndrome (IBS). The results suggest that some of these drugs, including antidepressants, may be linked to a small but measurable increase in the risk of death.
Published in Communications Medicine, the research draws on nearly 20 years of electronic health record data from more than 650,000 adults in the United States diagnosed with IBS. This makes it the largest real-world analysis to date focused on the long-term safety of IBS treatments.
IBS Overview and Long-Term Treatment Use
IBS is a chronic digestive condition that affects about 10% of people in the U.S. Although there is no cure, many patients manage symptoms through diet changes, behavioral therapy, 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.”
Large Study Examines IBS Medications and Mortality Risk
The researchers evaluated patients taking a range of treatments, including Food and Drug Administration-approved IBS medications, antidepressants, antispasmodics, and opioid-based antidiarrheal drugs such as loperamide and diphenoxylate, which are widely used in IBS care.
Their findings showed that long-term antidepressant use was associated with a 35% higher risk of death. Use of loperamide and diphenoxylate was linked to roughly double the risk of death compared with those not using these medications.
Study Shows Association, Not Direct Cause
The study does not prove that these medications directly cause death. Instead, the observed links may reflect a greater 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 reduce pain and ease symptoms. The study also found that other commonly recommended treatments, including FDA-approved medications and antispasmodics, were not associated with an increased risk of death.
Small Individual Risk but Important Considerations
Researchers emphasized that while the increased risk is statistically meaningful, the overall risk for any single 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 IBS Care
Rezaie noted that further studies are needed to confirm these findings and determine which patients may face the greatest risk. He also said future treatment guidelines should place more emphasis on the long-term safety of medications used to manage IBS.
In the meantime, he highlighted the importance of a personalized 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.
Reference: “Association of pharmacotherapy with all-cause mortality among patients with irritable bowel syndrome” by Sepideh Mehravar, Yee Hui Yeo, Mark Pimentel, Parnian Naji, Wee Han Ng, Nils Burger, Will Takakura and Ali Rezaie, 8 April 2026, Communications Medicine.
DOI: 10.1038/s43856-026-01498-6
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.
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4 Comments
I’m 60 now but when I was in my 20s I had debilitating IBS with spasms.
My IBS turned out to be due to the constipating effect of bovine serum albumin (cows milk produce), along with wheat intolerance.
Cows milk intolerance in adults is scarcely recognized by doctors which is strange as it’s so prevalent.
Wheat causes gas which is bad news if you’re constipated.
As soon as I stopped those things my bloating stopped and my bowels became normal again with minimal gas.
I use oat milk as I also developed an intolerance to soya after many years and take a calcium supplement.
My doc had me screen all the fod-map food which includes dairy. My irritant is wheat. It irritates my gut so much it can cause ulcers. If I’m wheat free 90% of my issues go away but I’m at risk for severe constipation (my gut is actually very slow! Or just so damaged after the years of wheat). I just started a med to increase the liquid to counter act that. 😅
ps the worst thing a person with cow’s milk intolerance can do is to take probiotic yogurt every day!
One thing I would like to know is if the study was able to see if the higher death risk correlated with those with more severe symptoms… After all, you’re more likely to try off label medications if your disease is severe and also not responding to more traditional treatments.
I wonder if there actually exists a control group of those with the same severity of disease that don’t do medications at all or a way to measure those that don’t turn to those alternatives to compare to those who stick with traditional treatments. (As in the higher risk of death might be more related to the severity of disease driving people to try different things).