Oral and parenteral anti-neuropathic agents for the management of pain and discomfort in irritable bowel syndrome: A systematic review and meta-analysis.

Background: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS.

Methods: We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes.

Key Results: We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics.

Conclusions And Inferences: Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.