A large U.S. study found some IBS medications are linked to a higher risk of death over time.
Antidepressants and certain antidiarrheal drugs showed the strongest associations.
Researchers stress the overall risk remains small and not cause-and-effect.
For millions of Americans living with irritable bowel syndrome (IBS), daily symptom management often means relying on medication. But a new large-scale study is raising questions about how safe some of those treatments are over the long haul.
Researchers from Cedars-Sinai examined commonly used IBS medications and found that some may be associated with a small but measurable increase in the risk of death. While that might sound alarming, experts emphasize that the overall risk for any one person remains low.
“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” researcher Ali Rezaie, M.D. said in a news release “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.”
How the study was conducted
To better understand long-term safety, researchers analyzed nearly two decades of electronic health records from more than 650,000 adults in the United States diagnosed with IBS. This makes it the largest real-world study of its kind.
The team compared patients taking different types of IBS treatments, including FDA-approved medications, antidepressants, antispasmodics, and opioid-based antidiarrheal drugs like loperamide and diphenoxylate.
Using this large dataset, researchers evaluated how these medications were associated with all-cause mortality over time.
Importantly, the study was observational, meaning it looked at patterns in existing data rather than testing medications in a controlled trial. That distinction matters: the findings show associations, not proof that the drugs directly cause harm.
What the researchers found
The results revealed clear differences between medication types. Long-term use of antidepressants was associated with about a 35% higher risk of death compared to non-use. Meanwhile, two commonly used antidiarrheal drugs — loperamide and diphenoxylate — were linked to roughly double the risk.
On the other hand, several other treatments did not show this association. Antispasmodics and certain FDA-approved IBS medications were not linked to increased mortality risk.
Researchers also noted that the increased risk may be tied to higher rates of serious health issues — such as cardiovascular events, falls, or stroke — among patients taking certain medications.
“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” Dr. Rezaie said. “Patients should speak with their healthcare provider about the safest and most effective options for managing their symptoms.
“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.”