Some IBS Medications Tied to Slightly Higher Risk of Early Death, Study Finds

A new study suggests that certain medications used to treat irritable bowel syndrome (IBS) may be linked to a slightly higher risk of early death, but experts stress the overall danger remains low for most people.

Researchers from Cedars-Sinai Health Sciences University in Los Angeles found that long-term use of two anti-diarrheal drugs—loperamide and diphenoxylate—was associated with about double the risk of death. They also reported that using antidepressants to manage IBS symptoms over a long period was linked to a 35% higher risk of death.

However, the scientists emphasized that while these numbers are statistically meaningful, the risk for any single person is small.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Dr. Ali Rezaie, medical director of the GI Motility Program at Cedars-Sinai and the study’s senior author, in a statement.

The findings, published April 8 in Communications Medicine, are still important, Rezaie noted. “Many patients are diagnosed with IBS at a young age and may remain on medications for years,” he said. “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.”

Dr. Rudolph Bedford, a gastroenterologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the research, pointed out that the study only shows a connection between the drugs and death, not a direct cause. “The risk to any one person is small, so there is no reason to panic,” he said. He added that IBS symptoms can be painful and even disabling, and for many patients, the benefits of medication outweigh the potential harm. “It’s about quality of life at the end of the day.”

The Cedars-Sinai team analyzed two decades of health records from nearly 670,000 adults in the United States. They called it the largest real-world study to date on the long-term safety of IBS treatments. The researchers looked at people taking FDA-approved IBS drugs, as well as antidepressants, antispasmodics, and opioid-based anti-diarrheal medications like loperamide and diphenoxylate.

The study did not prove these drugs directly cause death. Instead, the researchers suggested the higher risk might be linked to other problems, such as cardiovascular events, falls, or strokes. Notably, they found that antispasmodics and constipation treatments were not tied to an increased risk of death from any cause.

Dr. Ketan Thanki, a colorectal surgeon at MemorialCare Todd Cancer Institute at Long Beach Medical Center who was also not involved in the study, urged caution. “For now, we should still approach these findings with caution,” he said. “As the authors point out, correlation does not imply causation.” He advised people with IBS to discuss the findings with their doctors. “They should ask their physicians if they have other risk factors, which may also correlate to negative outcomes when taking the particular drugs they are on.”

Bedford agreed. “Patients and medical professionals need to be educated and be cognizant of the potential long-term effects,” he said. “They shouldn’t have a cavalier attitude about it.”

About 25 to 45 million people in the United States have IBS. Of those, roughly 31% report mild symptoms, 48% have moderate symptoms, and 20% have severe symptoms that can disrupt daily life. IBS is a functional GI condition, meaning it involves how the brain and gut interact. It is different from inflammatory bowel disease (IBD).

The exact cause of IBS is unknown, but it is linked to factors such as early-life stress, bacterial infections, food intolerances, anxiety, and depression. Common symptoms include diarrhea, constipation, and abdominal pain.

Experts say there are many ways to manage IBS beyond medications. Bedford noted that drugs can help reduce pain, cramps, diarrhea, and constipation. But lifestyle changes also play a big role. These include stress management, daily exercise, a low FODMAP diet (which limits certain hard-to-digest sugars), behavioral therapy to improve brain-gut communication, and probiotics.

Thanki emphasized that diet is one of the most powerful tools. “Start with dietary modification—low-FODMAP trial with dietitian guidance, add fiber, reduce fats, eat smaller portions, limit caffeine and alcohol, and avoid personal trigger foods,” he said. “This is one of the most effective ways to manage IBS.” He also recommended regular exercise, good sleep habits, and addressing mental health issues with therapies like hypnotherapy or cognitive behavioral therapy. He added that pelvic floor dysfunction, often overlooked, can be treated with physical therapy and biofeedback.