Gastrointestinal and Psychological Symptom Profiles May Predict Amitriptyline Response in IBS: Study
Exploratory analyses published in Clinical Gastroenterology and Hepatology identified distinct clusters of patients with irritable bowel syndrome (IBS) based on their gastrointestinal and psychological symptom profiles. These symptom clusters may help predict which patients are more likely to respond to low-dose amitriptyline and tolerate treatment better, potentially supporting a more personalised approach to IBS management. The study was conducted by Christopher J. and colleagues.
To determine if particular combinations of gastrointestinal and psychological symptoms at baseline predict response and tolerability, post hoc analyses were conducted among 401 participants who had been followed-up to 6 months of follow-up in the ATLANTIS trial cohort. Participants were divided into various clusters using latent class analysis (LCA) based on their somatic and psychological symptoms at baseline. Response differences between low-dose amitriptyline and placebo in particular clusters were analyzed by comparing mean changes in IBS-SSS score at 6 months.
Multivariate odds ratios (OR) and 95% confidence intervals (CI) for treatment response were calculated after adjusting for baseline covariates such as patient age, biological gender, baseline IBS score, and IBS stool subtype (IBS-C, IBS-D, or IBS-M). Trial drug discontinuation and side effect burden scores were determined at 6 months using the Antidepressant Side Effect Checklist.
Key findings:
- Cluster analysis of the 401 subjects involved in this study revealed that there is a four-cluster solution with unique efficacy and tolerability profiles.
- The four-cluster solution comprised of Cluster 1 consisting of patients with mild gastrointestinal and psychological symptoms, Cluster 2 comprising of patients with predominantly gastrointestinal symptoms and milder psychological symptoms, Cluster 3 comprising of patients with predominantly psychological symptoms and milder gastrointestinal symptoms, and Cluster 4 with patients suffering from more severe gastrointestinal and psychological symptoms.
- While the mean change in IBS-SSS by cluster according to treatment allocation was not statistically significant as a whole (treatment by cluster interaction, p = 0.76), Cluster 3 had a significantly greater mean decrease in IBS-SSS from baseline to 6 months with amitriptyline compared to placebo (−103.44 ± 117.81 vs. −61.89 ± 101.49; p = 0.045).
- Patients belonging to Cluster 4 (severe gastrointestinal and psychological symptoms) had a significantly higher rate of discontinuation of trial medication before 6 months (p = 0.0023).
- The mean Antidepressant Side Effect Checklist score was highest for Cluster 4 irrespective of the treatment allocation, though scores were higher among patients on amitriptyline than placebo in this cluster.
In summary, post hoc analysis of the ATLANTIS trial has established that IBS patients subtyped using symptoms of both gastrointestinal disturbances and psychological disorders form unique clinical subtypes that respond differently to low-dose amitriptyline. The implications of the research are that identifying these symptom phenotypes gives physicians the ability to predict treatment success and tolerance.
Reference:
Black, C. J., Wright-Hughes, A., Ow, P.-L., Alderson, S. L., Ridd, M. J., Foy, R., Chaddock, M., Guthrie, E. A., Everitt, H. A., Farrin, A. J., & Ford, A. C. (2026). Latent class analysis may predict patients with irritable bowel syndrome who respond to amitriptyline: Post hoc analyses from ATLANTIS. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2026.10.027
