Commun Med
Some IBS drugs tied to higher long-term mortality risk
Clinical takeaway: Long-term use of antidepressants and opioid-based antidiarrheals in IBS should be approached with caution.
IBS is often treated for years, but long-term safety data are limited. This study examined whether commonly used IBS treatments were associated with mortality in routine care.
Using a large U.S. electronic health record (EHR) database aggregating de-identified data from more than 100 health systems, researchers compared long-term outcomes across IBS medications.
In records from about 650,000 adults with IBS, antidepressant use was associated with a 35% higher risk of death (about 1.6% vs. 1.0%).
Loperamide and diphenoxylate were associated with roughly 2-fold higher mortality risk, with absolute rates around 2.1% vs. 1.0% for loperamide and 2.3% vs. 1.4% for diphenoxylate.
Antidepressants, while not FDA-approved for IBS, are frequently used off-label to reduce pain and modulate gut-brain signaling, while loperamide and diphenoxylate are FDA-approved for diarrhea and commonly used to manage IBS symptoms.
Several commonly used IBS treatments were not associated with increased mortality, including antispasmodics, rifaximin and bile acid sequestrants for IBS-D, and laxatives and secretagogues for IBS-C.
Also, FDA-approved IBS therapies were not associated with increased mortality, including lubiprostone, tenapanor, linaclotide, and plecanatide for IBS-C, and rifaximin, eluxadoline, and alosetron for IBS-D. However, these treatments are used less often with fewer than 20% of IBS-C and fewer than 10% of IBS-D patients receiving them.
“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai and senior author of the study.
Source: Mehravar S, et al. Commun Med. April 8, 2026. Association of pharmacotherapy with all-cause mortality among patients with irritable bowel syndrome