Ethosuximide may not be effective for the treatment of abdominal pain in irritable bowel syndrome

1. Ethosuximide was not superior to placebo for the treatment of abdominal pain in adults with irritable bowel syndrome.

Evidence Rating Level: 1 (Excellent)

Previous research suggested that increased activity or expression of T-type channels, particularly the Cav3.2 subtype, in the colonic mucosa contributes to visceral hypersensitivity in irritable bowel syndrome (IBS). The Cav3.2 channel is involved in pain transduction, and limited research has found that its inhibition alleviates pain. This study thus investigated the analgesic effect of the Cav3.2 channel blocker, ethosuximide, in IBS-related abdominal pain. This multicenter, double-blinded, randomized clinical trial was conducted between February 2018 and February 2022 and included adults with IBS (meeting Rome IV criteria). Participants were randomized to receive either ethosuximide or a placebo for 12 weeks and followed up for 3 weeks. The primary outcome responder rate, defined as a reduction of at least 30% in mean weekly abdominal pain intensity from baseline and a Subject Global Assessment (SGA) score of at least 4 out of 5 (i.e., considerably relieved or completely relieved). Of the 124 patients randomized (mean [SD] age, 4.7 [14.9] years; 72 [58.1%] women), 64 were in the ethosuximide group and 60 in the placebo group. Responder rates did not differ significantly between groups (17/64 [26.6%] for ethosuximide vs 14/60 patients [23.3%] for placebo; relative risk, 1.14; 95% CI, 0.61-2.11). Compared to placebo, ethosuximide was less well tolerated, with higher discontinuation rates and induced more adverse events. Overall, this study found that ethosuximide was not superior to placebo for the treatment of abdominal pain in adults with IBS and was associated with reduced tolerability. These findings do not support the use of ethosuximide for managing IBS-related pain.

Click here to read this study in JAMA Network Open

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