Pharmacologic therapies for IBS-C
Linaclotide is a guanylate cyclase-C agonist with an indication for treatment of IBS-C. A double-blind, parallel-group, placebo-controlled trial found that the percentage of patients who experienced a decrease in abdominal pain was nearly 25%, with statistically significant improvements in bloating, straining, and stool consistency over a 26-week period.20 In a report on 2 phase 3 trials, researchers found that linaclotide improved global symptom scores and significantly decreased abdominal bloating and fullness, pain, cramping, and discomfort vs placebo. Diarrhea was the most commonly reported adverse event in patients with severe abdominal symptoms (18.8%-21%).21
Lubiprostone is a prostaglandin E1 analogue that activates type-2-chloride channels on the apical membrane of epithelial cells in the intestine. In a combined analysis of 2 phase 3 randomized trials, lubiprostone was administered twice daily for 12 weeks vs placebo and patients were asked to describe how they felt after the trial period. Survey responders reported significant improvements in global IBS-C symptoms (17.9% vs 10.1%; P=.001).22 A meta-analysis of studies on lubiprostone found that diarrhea, nausea, and abdominal pain were the most common adverse effects, but their occurrence was not that much greater than with placebo.23
Diet and probiotics can play a significant role
The role of dietary components in the treatment of IBS is gaining increasing attention. Such components can have a direct effect on gastric and intestinal motility, visceral sensation, immune activation, brain-gut interactions, and the microbiome. Current evidence suggests that targeted carbohydrate and gluten exclusion plays a favorable role in the treatment and symptomatic improvement of patients with IBS.24
A 2014 study conducted in Australia showed that a diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), which is characterized by avoiding foods containing gluten and those that are high in fructose, reduced overall GI symptom scores (including scores involving abdominal bloating, pain, and flatus) in patients with IBS compared to those consuming a normal Australian diet.25 The International Foundation for Functional Gastrointestinal Disorders’ Web site provides a detailed guide to low FODMAP foods and can be found at: http://www.aboutibs.org/low-fodmap-diet.html.
Probiotics are now commonly used in the symptomatic treatment of many upper and lower GI disorders. While much anecdotal evidence exists to support their benefit, there is a paucity of large-scale and rigorous research to provide substantial outcomes-based evidence. The theory for their use is that they support regulation of the gut microbiome, which in turn improves the imbalance between the intestinal microbiome and a dysfunctional intestinal barrier.
A 2014 randomized, double-blind, placebo-controlled trial involving multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) found that patients who received probiotics had significantly reduced symptoms of IBS after 4 weeks compared with placebo, and modest improvement in abdominal pain and discomfort as well as bloating.26 One study involving 122 patients from 2011 found that B. bifidum MIMBb75 reduced the global assessment of IBS symptoms by -88 points (95% CI, -1.07 to -0.69) when compared with only -0.16 (95% CI, -.32 to 0.00) points in the placebo group (P<.0001).27 MIMBb75 also significantly improved the IBS symptoms of pain/discomfort, distension/bloating, urgency, and digestive disorder. And one randomized, double-blind, placebo-controlled study involving 67 patients found that QOL scores improved two-fold when patients took Saccharomyces boulardii (15.4% vs 7.0%; P<.05).28
Dried plums or prunes have been used successfully for decades for the symptomatic treatment of constipation. A single-blinded, randomized, cross-over study compared prunes 50 g/d to psyllium fiber 11 g/d and found that prunes were more efficacious (P<.05) with spontaneous bowel movements and stool consistency scores.29
Peppermint oil has been studied as an alternative therapy for symptoms of IBS, but efficacy and tolerability are concerns. A meta-analysis of randomized controlled trials with a minimum duration of 2 weeks found that compared with placebo, peppermint oil provided improvement in abdominal pain, bloating, and global symptoms, but some patients reported transient heartburn.30 A 4-week, randomized, double-blind, placebo-controlled clinical trial sponsored by IM HealthScience found a novel oral formulation of triple-enteric-coated sustained-release peppermint oil microspheres caused less heartburn than was reported in the previous study, but still significantly improved abdominal symptoms and lessened pain on defecation and fecal urgency.31
CASE › Suspecting IBS-D, the FP ordered a complete blood count, tissue transglutaminase antibodies, and a stool culture, all of which were unremarkable. Ms. S has been trying to follow a low FODMAP diet and has been taking some over-the-counter probiotics with only minimal relief of abdominal bloating and cramping and no improvement in stool consistency. Her FP started her on eluxadoline 100 mg twice daily with food. After 12 weeks of therapy, she reports significant improvement in global IBS symptoms and nearly complete resolution of her diarrhea.
*Amber S is a real patient in my practice. Her name has been changed to protect her identity.
CORRESPONDENCE
Joel J. Heidelbaugh, MD, FAAFP, FACG, Ypsilanti Health Center, 200 Arnet Suite 200, Ypsilanti, MI 48198; jheidel@med.umich.edu.