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

Abstract

Background: Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficultto-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.

Pain in irritable bowel syndrome: Does anything really help?

“…While the recent systematic review by Lambarth et al 1 studied anti-neuropathic agents notably amitriptyline and duloxetine, other systematic reviews have also investigated the effectiveness of antidepressants in the treatment of pain in IBS. In one systematic review, the beneficial effect of tricyclic antidepressants (TCA) on abdominal pain [RR of not improving of 0.59 (95% CI: 0.42-0.83)] was observed, but such benefit was not demonstrated with selective serotonin reuptake inhibitors (SSRIs) [RR of not improving of 0.64 (95% CI: 0.32-1.27)].…”

“…In the systematic review and meta-analysis published in this issue of the journal, 1 Lambarth et al 2 examined the literature on the role of oral and parenteral anti-neuropathic agents in the management of pain in patients with irritable bowel syndrome (IBS).…”

“…Some of the limitations of the presented data include the small sample size of some of the included studies, the lack of subgroup analysis, and the low number of studies included in the meta-analysis. Overall, through their analysis, Lambarth et al 1 have provided valuable insight into the role of anti-neuropathic, analgesic agents in the management of pain in IBS.…”

Management of bloating

“…In a barostat study to assess the effects of gabapentin on rectal sensitivity to distention, gabapentin, but not placebo, increased the threshold for bloating in patients with diarrhea‐predominant IBS 77 . The effects of Alpha 2 Delta (α(2)δ) ligands on abdominal pain have been studied in different clinical trials, but the effect of these drugs specifically on abdominal bloating remains unclear 78 …”

“…77 The effects of Alpha 2 Delta (α(2)δ) ligands on abdominal pain have been studied in different clinical trials, but the effect of these drugs specifically on abdominal bloating remains unclear. 78…”