IBS Pharmacotherapy Safety: AMJ, March 2026

Introduction

Choosing drug therapy for irritable bowel syndrome (IBS) requires balancing symptom benefit against treatment-related adverse effects. While clinicians often use the number needed to treat (NNT) to compare efficacy, the number needed to harm (NNH) offers an equally important perspective by estimating how many patients need to be treated before one stops therapy because of an adverse event. This systematic review and meta-analysis evaluated the safety of commonly used IBS medications by focusing on discontinuation due to adverse events, a pragmatic marker of tolerability.

Summary

This meta-analysis included 54 placebo-controlled clinical trials involving 33,538 patients and assessed IBS-C, IBS-D, and global symptom therapies. The primary outcome was NNH, derived from treatment discontinuation due to adverse events.

Among IBS-C therapies, the NNH was 35 for linaclotide, 53 for lubiprostone, 59 for plecanatide, 58 for tegaserod, and 16 for tenapanor. For IBS-D therapies, the NNH was 14 for alosetron and 32 for eluxadoline, while rifaximin and ramosetron had negative, nonsignificant NNH values, meaning placebo groups had numerically higher discontinuation rates than active treatment groups. For global IBS symptom therapy, tricyclic antidepressants had an NNH of 24.

Overall, tenapanor, alosetron, and tricyclics had the greatest risk of treatment discontinuation due to adverse events, whereas rifaximin appeared to be the safest pharmacotherapy studied. The most common adverse effects reflected mechanism of action: diarrhea and nausea for IBS-C drugs, constipation for IBS-D drugs, and anticholinergic or sedative effects for tricyclics. Importantly, many adverse events were transient and nonserious.

This study emphasizes that IBS treatment decisions should not rely on efficacy alone. Safety, tolerability, and patient preference should be central when selecting among multiple reasonable drug options.