# New Developments in the Treatment of Irritable Bowel Syndrome



## eric (Jul 8, 1999)

FYINew Developments in the Treatment of Irritable Bowel Syndrome"From Medscape GastroenterologyIBS and Chronic Constipation Expert ColumnNew Developments in the Treatment of Irritable Bowel SyndromePosted 08/02/2006Philip S. Schoenfeld, MD, MSEd, MSc (Epi) Introduction and ContextNew data regarding the efficacy and safety of treatments for irritable bowel syndrome (IBS) were presented during Digestive Disease Week (DDW) 2006. Application of these data should lead to important improvements in the treatment of patients with IBS. Gastroenterologists and primary care physicians must also understand the pathophysiologic defects present in IBS patients because an understanding of these defects supports the rationale for different IBS therapies. New data on this underlying pathophysiology of IBS have been published in the past year. These data indicate that patients with IBS have defects in serotonin signaling in the enteric nervous system; patients with IBS with constipation (IBS-C) have low levels of serotonin in response to a meal stimulus, whereas patients with IBS with diarrhea (IBS-D) have unusually high levels of serotonin in response to a meal. This implies that IBS-C patients may have defects in serotonin release, while IBS-D patients may have defects in serotonin reuptake after release.[1] Additionally, patients with IBS may have low levels of inflammation in the colonic mucosa.[2] This inflammation may be due to subtle changes in the bacterial flora of the colon; other experts have proposed that most IBS symptoms are due to bacterial overgrowth in the small intestine.[3]This article reviews the most recent data regarding therapeutic strategies for IBS, with specific focus on studies presented during DDW 2006."FYIRifaximinRecent data suggest that IBS patients demonstrate an inflammatory state characterized by abnormal interleukin ratios,[2] infiltration of lymphocytes into the colonic mucosa, and degeneration of neurons in the myenteric plexus. Additionally, 10% to 84% of patients with IBS may have small intestinal bacterial overgrowth, as confirmed by lactulose breath tests. Therefore, there is increasing evidence that inflammation in the colonic (or small intestinal) mucosa may contribute to IBS symptoms. Given these data, antibiotics or probiotics could be helpful in the treatment of IBS.During DDW 2006, Pimentel and colleagues[9] presented data from an RCT involving 87 patients with IBS on the use of supratherapeutic doses of rifaximin, a nonabsorbed antibiotic, for the treatment of their IBS. Subjects received rifaximin 400 mg orally thrice daily or placebo for 10 days. Study outcomes included improvement in abdominal discomfort, bloating, diarrhea symptoms, and constipation symptoms as measured by a 100-point visual analog scale. End points were assessed 1 week after antibiotic therapy was completed and then 10 weeks after completion of antibiotic therapy. One week after completing antibiotic therapy, abdominal discomfort and constipation were not improved for rifaximin-treated patients vs placebo-treated patients, but bloating and diarrhea were significantly improved. Ten weeks after antibiotic therapy was completed, the investigators evaluated those patients who demonstrated a 50% improvement in specific symptoms (as measured on the 100-point visual analog scale). Rifaximin-treated patients were more likely to demonstrate a 50% improvement in their visual analog scale scores compared with placebo-treated patients for all outcomes (Figure 2). Figure 2. (click image to zoom) Improvement in IBS symptoms 10 weeks after rifaximin therapy.* Two important questions remain. First, it is unclear why no significant improvement in abdominal discomfort or constipation was seen 1 week after completion of therapy but was seen 10 weeks after therapy. In the future, it would be helpful if similar studies of rifaximin used satisfactory relief of global IBS symptoms measured with a binary response (yes/no) as one of the study end points, as this is a more standard end point to assess clinically important improvement in IBS symptoms. Second, on the basis of these data presented in abstract form, it is still unclear whether the improvement in IBS symptoms is sustained after discontinuation of antibiotic therapy. This is an important concern because a similar trial in patients with functional bloating and/or IBS demonstrated that much of the improvement in symptoms was rapidly lost after discontinuation of antibiotics.[10] In this trial, patients were randomized to receive a 10-day course of rifaximin 400 mg orally twice daily vs placebo. The primary end point was any improvement in bloating symptoms. Rifaximin-treated patients were more likely to have any improvement in bloating symptoms compared with placebo-treated patients (Figure 3). However, this improvement was not sustained. Within 10 days of discontinuing antibiotic use, most rifaximin-treated patients no longer noted any improvement in their bloating symptoms. Figure 3. (click image to zoom) Effect of rifaximin in patients with bloating.Key: After Tx = the percentage of responders immediately after completion of antibiotic therapy; Post-Tx = the percentage of responders 10 days after completion of the antibiotic therapy Given the available data, this physician does not think that antibiotics should be considered a primary therapy for patients with IBS. Additional research must be completed in multiple centers and published in full manuscript form before clinicians change their approach to the management of these patients. Treatment with antibiotics and probiotics may be considered supplemental or secondary approaches in the refractory IBS patient. Physicians should also keep in mind that rifaximin is currently only FDA-approved for the treatment of infectious diarrhea at a dose of 200 mg twice daily for 3 days, which is a much lower dose and shorter course than has been used in the IBS trials. http://www.medscape.com/viewarticle/540226_5


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