Long-Term Study Links Antidepressants and Opioid-Based IBS Drugs to Increased Mortality Risk

Cedars-Sinai researchers find a 35% higher mortality risk for IBS patients using antidepressants and double the risk for certain antidiarrheals.

By: AXL Media

Published: Apr 8, 2026, 11:05 AM EDT

Source: Information for this report was sourced from Cedars-Sinai Medical Center

Addressing the Long-Term Safety Gap in IBS Maintenance

Irritable Bowel Syndrome (IBS) affects approximately 10% of the U.S. population, often necessitating decades of pharmacological management. However, most clinical trials governing these treatments last for less than one year, leaving a critical void in data regarding long-term safety. A landmark study published in Communications Medicine on April 8, 2026, has begun to fill this gap. Utilizing nearly 20 years of electronic health records, researchers at Cedars-Sinai Health Sciences University conducted the largest real-world analysis to date, uncovering "small but measurable" increases in mortality associated with some of the most frequently prescribed non-IBS-specific treatments.

The Mortality Risks of Antidepressants and Opioid-Based Antidiarrheals

The study’s most striking findings involve the use of antidepressants and common antidiarrheal medications like loperamide and diphenoxylate. Although antidepressants are not FDA-approved specifically for IBS, they are widely used off-label to modulate gut-brain signaling and reduce chronic pain. The researchers found that long-term antidepressant use was associated with a 35% higher risk of death. Even more concerning, the use of opioid-based antidiarrheals was associated with roughly double the risk of death compared to non-users. These elevated risks were often linked to higher frequencies of adverse events such as cardiovascular incidents, falls, and strokes among the exposed patient population.

Safe Harbors: FDA-Approved Treatments and Antispasmodics

Importantly, the study provided reassurance regarding several other classes of medication. Treatments specifically FDA-approved for IBS, alongside common antispasmodics, showed no associated increase in mortality risk. This distinction suggests that the underlying mechanisms or side-effect profiles of antidepressants and opioid-based drugs may be uniquely problematic when used long-term for gastrointestinal distress. Senior author Dr. Ali Rezaie emphasized that while the findings are significant at a population level, the absolute risk to an individual patient remains relatively small, meaning patients should not immediately discontinue prescribed regimens without professional consultation.