Use of antidepressants along with IBS medications linked to increased mortality: Study
A study published in Communications Medicine has reported that in patients with irritable bowel syndrome (IBS), the use of antidepressants and certain antidiarrheal medications is associated with a higher risk of mortality. The study was conducted by Sepideh M. and colleagues.
IBS is a common gastrointestinal condition that is commonly known for being expensive to treat as well as significantly affecting the quality of life of millions of affected individuals. Although several pharmacological agents have been proposed for treating symptoms such as abdominal pain, diarrhea, and constipation, very little evidence is available regarding the effects of these treatments on survival rates. To explore the connection between common medications used in the treatment of IBS and overall mortality, the authors of the current paper decided to conduct their study using the national U.S. electronic health record database.
The research is based on the principles of a retrospective cohort study with the application of 1:1 propensity score matching technique to provide an even distribution of medication users and non-users in order to compare the effects and outcomes of each group. In total, there are 669,083 individuals aged between 18 and 65 years who have been diagnosed with IBS. According to the pharmacotherapy used by patients, detailed subgroup analyses were performed for the people with IBS-D and IBS-C disorders.
For each patient, the study involved an evaluation of the period beginning from the time when medication recommended by guidelines was prescribed. To conduct a reliable analysis and obtain statistically significant results, the Cox proportional hazards model and the concept of the target trial emulation were applied with respect to the main parameter measured, the all-cause mortality rate among patients.
Key findings:
- There were considerable discrepancies regarding the safety profiles between drug groups. The use of antidepressants was significantly related to higher hazards of overall mortality, having the HR value of 1.35 (95% CI, 1.26-1.45).
- Patients using antidepressants experienced 1.6% mortality rate, which was significantly higher than 1.0% among controls.
- Moreover, this trend was evident among antidepressants' subgroups and demographic subgroups. However, in contrast, the HR of 0.95 (95% CI, 0.89-1.00) for antispasmodics indicates that their application is not associated with a higher risk of mortality.
- For the treatment of IBS-D, the highest risks of mortality were associated with the mu receptor agonists.
- No link was found between the use of rifaximin, eluxadoline, and cholestyramine and mortality rates; however, diphenoxylate and loperamide showed an extremely high risk of death (HR=1.89; 95% CI, 1.02-3.51) and (HR=2.39; 95% CI, 1.48-3.90), respectively.
This comprehensive study is significant because it presents important information about certain common drug therapies used in IBS being associated with an increased risk of death due to all causes. There are now some fears raised concerning the use of both antidepressant drugs and mu receptor agonists in treating IBS due to this study. Although this study has a very large sample size and a sufficiently long period of follow up, it cannot replace other future studies in order to determine the biological mechanisms behind the increased risk of death.
Reference:
Mehravar, S., Yeo, Y.H., Pimentel, M. et al. Association of pharmacotherapy with all-cause mortality among patients with irritable bowel syndrome. Commun Med 6, 176 (2026). https://doi.org/10.1038/s43856-026-01498-6
