A new large-scale study led by researchers at Cedars-Sinai University of Health Sciences is raising questions about the long-term safety of some drugs commonly used to treat irritable bowel syndrome (IBS). The findings suggest that certain drugs, including antidepressants, may be associated with a small but measurable increased risk of death.
Published in communication medicineThe study analyzed nearly 20 years of electronic health records of more than 650,000 U.S. adults diagnosed with IBS. This made this the largest real-world study to date focused on how safe these treatments are over the long term.
Understand IBS and its treatments
IBS is a chronic digestive disease that affects approximately 10% of people in the United States. There is no cure, but symptoms can often be managed with dietary changes, behavioral therapy, and medication.
“Many patients are diagnosed with irritable bowel syndrome at a young age and may remain on medication for years,” said Ali Rezai, M.D., medical director of the Gastrointestinal Motility Program at Cedars-Sinai and senior author of the study. “However, because most clinical trials of these drugs last less than a year, little is known about their long-term safety. This study begins to address that gap.”
Study finds increased risk with certain IBS drugs
The researchers tested patients using a variety of treatments, including Food and Drug Administration-approved IBS drugs, antidepressants, antispasmodics, and opioid-based antidiarrheal drugs 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% increased risk of death. The use of loperamide and diphenoxylate was associated with approximately twice the risk of death compared with not taking these drugs.
What we know and what we don’t know from the survey results
Importantly, this study does not prove that these drugs directly cause death. Rather, this association may reflect a higher likelihood of people ingesting serious health complications such as cardiovascular events, falls, and stroke.
Although antidepressants are not specifically approved by the FDA for IBS, they are often prescribed to manage pain and reduce the severity of symptoms. Researchers noted that other commonly recommended treatments, such as FDA-approved IBS drugs and antispasmodic drugs, were not associated with an increased risk of death.
Small personal risk, but important considerations
The researchers emphasized that although the increased risk is statistically significant, the overall risk for a single patient remains low.
“People with IBS should not panic, but they should understand and weigh the small but meaningful risks when considering long-term treatment,” said Rezai, director of bioinformatics in the Medically Associated Science and Technology (MAST) program at Cedars-Sinai. “Patients should discuss the safest and most effective options for managing their symptoms with their health care provider.”
Seeking more research and personalized care
Rezaie emphasized that additional research is needed to confirm these findings and determine which patients may be most vulnerable. He also emphasized the need for future treatment guidelines to improve the long-term safety of drugs frequently used for IBS.
During that time, he encouraged a more individualized approach to care.
“Treatment for patients with IBS should focus on identifying the underlying cause and using the safest, evidence-based options available, rather than relying on a single type of drug for long-term management,” Rezai said.
Other authors at Cedars-Sinai include Sepideh Mehravar, MD, Yee Hui Yeo, MD, and Mark Pimentel, MD.
Other authors include Parnian Nagy, MD, Wee Hung Ng, PhD, Nils Berger, PhD, and Will Takakura, MD.
Conflict of interest: Mark Pimentel is also a consultant for and receives grant support from Bausch Health. Ali Rezaie reports serving as a consultant for Bausch Health and Ardelyx. Additionally, Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech. Ali Rezaie and Mark Pimentel own shares in Gemelli Biotech and Good LFE. The remaining authors have not disclosed any discrepancies.
