Ethosuximide did not improve abdominal pain compared with placebo in patients with irritable bowel syndrome and was associated with higher discontinuation rates due to adverse events, according to a randomized clinical trial published in JAMA Network Open.
Irritable bowel syndrome is a disorder of gut-brain interaction characterized by recurrent abdominal pain and altered bowel habits. Investigators evaluated whether inhibition of T-type calcium channels could reduce pain in this population.
In the multicenter, double-blind, placebo-controlled randomized clinical trial, 124 adults meeting Rome IV criteria for irritable bowel syndrome were randomly assigned to receive ethosuximide (n = 64) or placebo (n = 60) for 12 weeks. Eligible patients reported a mean abdominal pain intensity of at least four on a 10-point scale during a seven-day run-in period.
The primary end point was the responder rate, defined as at least a 30% reduction in mean abdominal pain intensity from baseline and a Subject Global Assessment of Relief score of at least four, indicating considerable or complete relief.
In the intention-to-treat analysis, 27% of patients in the ethosuximide group met responder criteria compared with 23% in the placebo group, a difference that was not statistically significant. Findings were similar in the modified intention-to-treat analysis. Although the per-protocol analysis showed higher response rates among patients who completed treatment, investigators noted that the higher discontinuation rate in the ethosuximide group limited interpretation of that result.
Treatment discontinuation occurred in 47% of patients assigned to ethosuximide compared with 22% assigned to placebo. Discontinuations due to adverse events were more frequent in the ethosuximide group. Overall, 463 adverse events were reported, with more events occurring among patients receiving ethosuximide. Common treatment-related adverse events included headache, sleep disturbance, fatigue, nausea, abdominal pain, and dizziness.
Secondary end points, including changes in irritable bowel syndrome severity and quality of life scores, did not differ between groups in the intention-to-treat analysis.
The authors concluded that ethosuximide was not associated with improved abdominal pain compared with placebo and was less well tolerated. They noted that future research may evaluate more selective T-type calcium channel modulators with improved safety profiles.
The study was supported by the French Ministry for Health and the Société Française d’Etude et de Traitement de la Douleur. Several authors reported receiving personal fees from pharmaceutical companies outside the submitted work; additional disclosures are reported in the article.
Source: JAMA Network Open