35% Higher Mortality Risk Observed With Certain IBS Therapies

Irritable bowel syndrome (IBS) is a common digestive condition that can significantly impact daily life, often requiring long-term medication to manage symptoms like diarrhea, constipation and abdominal pain. However, the long-term safety of many of these treatments has remained uncertain. A large U.S.-based study published in Communications Medicine set out to better understand how commonly prescribed IBS medications may be linked to overall survival.

“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said senior investigator Ali Rezaie, M.D., medical director of the GI Motility Program at Cedars-Sinai. “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.”

Investigators analyzed electronic health records from more than 669,000 adults with IBS between 2005 and 2023. They compared patients taking different medications using a matched study design to account for factors like age, health status and demographics. The main goal was to evaluate whether certain treatments were associated with a higher risk of death from any cause over time.

The results showed that antidepressants, which are frequently prescribed for IBS to help regulate gut-brain signaling and pain, were associated with a 35% higher risk of death compared with those not taking them. This pattern was consistent across different types of antidepressants and patient groups.

Among patients with diarrhea-predominant IBS (IBS-D), two commonly used antidiarrheal medications (loperamide and diphenoxylate) were also linked to a higher risk of death. In contrast, other IBS-D treatments, including bile acid binders, antibiotics and newer therapies, did not show this association.

For constipation-predominant IBS (IBS-C), commonly used treatments like osmotic laxatives and prescription medications designed to increase fluid in the intestines were not associated with increased mortality. Similarly, antispasmodic medications used to relieve cramping showed no increased risk.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” noted Rezaie. “Patients should speak with their health care provider about the safest and most effective options for managing their symptoms.”

Investigators mentioned that the study has several notable strengths that increase confidence in its findings. It followed a large, nationwide group of patients over a long period of time, including individuals from different health care settings and insurance types. The team also used advanced statistical methods to carefully compare treatment groups and account for many potential differences between patients. By designing the study to mimic a clinical trial and including safeguards, like time delays between treatment and outcomes, they aimed to reduce common biases and better reflect real-world medication effects.

However, there are also important limitations to consider. Because this was an observational study based on electronic health records and insurance claims data, it may include inaccuracies such as misdiagnosis or missing information. Not all factors that could influence outcomes, like lifestyle or disease severity, can be fully captured, which means some results may be affected by unmeasured variables. Additionally, the data source used has certain restrictions, including a limited ability to confirm medication adherence or determine the exact cause of death.

While the study provides valuable real-world insights, its findings should be interpreted with caution and confirmed through further research using more detailed data and methods.

“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 concluded.