Objective: The aim of the study was to investigate the clinical efficacy and safety of ketotifen for the treatment of irritable bowel syndrome with diarrhea (IBS-D).
Methods: A total of 108 enrolled IBS-D patients were randomly divided into a ketotifen group (n = 55) and a control (placebo) group (n = 53). The patients in the ketotifen group received ketotifen tablets (1 mg, oral) two times daily; patients in the control group received oral placebo for 8 weeks. Before and after 8 weeks of treatment, gastrointestinal symptoms, anorectal sensory function and the number and activity status of mast cells were assessed for both groups.
Results: (1) The overall effective rate of gastrointestinal symptom improvement in the ketotifen group was significantly higher than that in the control group (76.4 vs. 37.7%, P < 0.001). (2) First sensation, defecation urgency and discomfort/pain threshold in the ketotifen group improved significantly after treatment (P < 0.05); no significant changes were observed in the control group (P > 0.05). (3) In the ketotifen group, the number of mast cells in the terminal ileum decreased, and the percentages of degranulated mast cells in the sigmoid colon, ascending colon and terminal ileum decreased significantly after treatment compared with before treatment; these differences were statistically significant (P < 0.01). In the control group, the number of mast cells and the percentages of degranulated mast cells in various sites did not change significantly before and after treatment (P > 0.05). (4) Six patients (10.9%) in the ketotifen group experienced drowsiness and fatigue, but the symptoms disappeared after 1 week of treatment.
Conclusion: Ketotifen significantly alleviated gastrointestinal symptoms and improved visceral hypersensitivity in patients with IBS-D. The therapeutic effect of ketotifen is related to a reduced number and decreased activity of mast cells in the intestinal mucosa, especially in the terminal ileum.