A large, long-term study has found that certain medications commonly used to treat Irritable Bowel Syndrome (IBS), including antidepressants and some anti-diarrhoeal drugs, may be associated with a small but measurable increase in the risk of death, although the overall risk to individual patients remains low.
Despite the findings, experts cautioned against alarm. The relative increase in risk, though statistically significant, translates into a small absolute risk for most patients.
The study, led by researchers at Cedars-Sinai Medical Center and published in Communications Medicine, analysed nearly two decades of electronic health records from over 6.5 lakh adults in the United States. It is among the largest real-world investigations into the long-term safety of IBS treatments.
IBS is a chronic gastrointestinal disorder that affects a significant proportion of the population and is typically managed through dietary changes, behavioural therapies, and medication. However, there is no definitive cure, and many patients remain on treatment for prolonged periods.
“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said Ali Rezaie, 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.”
The researchers evaluated a range of treatments, including drugs approved by the Food and Drug Administration (FDA), as well as antidepressants, antispasmodics, and opioid-based anti-diarrhoeal medications such as loperamide and diphenoxylate.
The findings indicated that long-term use of antidepressants was associated with a 35% higher risk of death, while the use of loperamide and diphenoxylate was linked to nearly double the risk. At the same time, other commonly prescribed therapies, including FDA-approved medications for IBS and antispasmodics, were not associated with increased mortality.
The study, however, does not establish a direct causal link between these medications and death. Researchers noted that the associations may reflect a higher incidence of adverse health events—such as cardiovascular complications, falls, and stroke—among patients taking these drugs.
“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.”
Antidepressants, while not specifically approved for IBS, are often prescribed to help manage pain and improve symptom control. The study highlights the need for careful evaluation of such off-label use, particularly over extended durations.
Researchers emphasised that the findings underline a broader gap in medical knowledge regarding the long-term safety of commonly used therapies. Most clinical trials for IBS medications are short-term, leaving uncertainties about prolonged use.
Dr. Rezaie called for further research to validate the findings and identify patient groups that may be more vulnerable to adverse outcomes. He also suggested that future treatment guidelines should more clearly address long-term safety considerations.
In the interim, he advocated for a more individualised 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,” he said.
