TOPLINE:

Ethosuximide, a T-type calcium channel blocker, showed no significant benefit in reducing the intensity of irritable bowel syndrome (IBS)-related abdominal pain compared with placebo. The trial found higher discontinuation rates in the ethosuximide group due to adverse events.

METHODOLOGY:

• T-type calcium channels, particularly Cav3.2, are implicated in pain modulation and overexpressed in patients with IBS; one study has suggested potential benefits of a Cav3.2 channel blocker, but the evidence is limited.
• Researchers conducted a randomized clinical trial (February 2018-2022) in 10 French academic gastroenterology departments to assess the effect of ethosuximide on IBS-related abdominal pain.
• Patients with IBS were randomly assigned to receive ethosuximide or a matched placebo, administered daily for 12 weeks, in addition to their usual IBS treatments.
• The primary composite outcome was the responder rate, defined as a reduction of ≥ 30% in the mean weekly abdominal pain intensity and a Subject’s Global Assessment of Relief score of at least 4 out of 5.
• Adverse events were monitored through patient diaries and phone calls, with additional follow-up for delayed events.

TAKEAWAY:

• Researchers included 124 adult patients (mean age, 43.7 years; 58.1% female) who met the Rome IV criteria for IBS, had a mean pain intensity of at least 4 out of 10, and were unresponsive to standard treatments; of them, 64 were assigned to the ethosuximide group and 60 to the placebo group.
• No significant difference in responder rates was found between the ethosuximide and placebo groups in the intention-to-treat analysis.
• The severity of IBS (assessed using the irritable bowel severity scoring system) and quality-of-life scores did not differ between groups.
• The ethosuximide group had higher discontinuation rates than the placebo group (46.9% vs 21.7%; P = .003) primarily due to adverse events (23.4% vs 10.0%; P = .046). The most common treatment-related adverse events in the ethosuximide group included headaches, sleep disturbances, and fatigue.

IN PRACTICE:

“[T]hese results suggest that ethosuximide cannot be recommended for the treatment of IBS-related abdominal pain because of its poor tolerability and modest efficacy,” the authors of the study wrote.

SOURCE:

The study was led by Nicolas Kerckhove, PhD, University Hospital of Clermont-Ferrand and Université Clermont Auvergne, Clermont-Ferrand, France. It was published online in January 2026, in JAMA Network Open.

LIMITATIONS:

The dropout rate in the ethosuximide group was high owing to poor tolerability. Visceral sensitivity was not assessed, and plasma ethosuximide concentrations were not measured, which may have aided in the characterization of responders and nonresponders.

DISCLOSURES:

The study was supported by the French Ministry for Health and the Société Française d’Etude et de Traitement de la Douleur. Some authors reported receiving personal fees from various pharmaceutical, healthcare, and medical technology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.