Relooking at Medications for Constipation-Predominant Irritable Bowel Syndrome

A recent study (CJ Black et al. Gastroenterol 2018; 155: 1753-63) examined the effectiveness of secretagogues for constipation-predominant irritable bowel syndrome (IBS-C).  The authors conducted a systematic review and network meta-analysis with 15 eligible randomized controlled trials (8462 patients).

Key findings:

  • Linaclotide (290 mcg per day) was ranked first in efficacy using the end point recommended by the FDA for IBS-C trials
  • Tenapanor (50 mg twice a day) was ranked first for bloating
  • Plecanatide (6 mg per day) ranked first for safety
  • Diarrhea was significantly more common with all of the secretagogues except for lubiprostone; nausea was significantly more common with lubiprostone

The authors acknowledge the limitations in comparing medicines without direct head-to-head trials (which may never occur).  They state that linaclotide being superior to other treatments had a probability of 88%.

My take: This study indicates that linaclotide may be more likely to be effective than other IBS-C medications; all of these secretagogues have been shown to be superior to placebo.

In this same issue, pgs 1666-9 (J Ruddy), a patient describes her long journey with abdominal pain/GI symptoms.  She describes her initial experiences with physicians who were dismissive and not attentive. Ultimately, a physician listened to her and  helped her improve after explaining that she had a postinfectious IBS and provided treatment.

Related study: S Ishague et al. BMC Gastroenterol 2018; 18:71.  This randomized controlled trial which compared a multistrain probiotic (Bio-Kult, n=181) to placebo (n=179).  The probiotic group had a 69% decrease in abdominal pain compared to a 47% decrease in placebo group.

Sunrise, Death Valley

Evidence-Based IBS Treatment Recommendations from ACG

A recent  American College of Gastroenterology Task Force conducted a systematic review (AC Ford et al. The American Journal of Gastroenterology 2018;113:1–18 ) to update management recommendations for irritable bowel syndrome -Link:

American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome

The highlights of this report are summarized at Gastroenterology & Hepatoloy: Highlights of the Updated Evidence-Based IBS Treatment Monograph

A few excerpts:

“There have been numerous studies performed on the roles of diet and dietary manipulation in IBS. Three fairly firm conclusions were made following the review of these studies: (1) the low–fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet seems to be effective for overall IBS symptom improvement; (2) a gluten-free diet is not effective for symptom improvement; and (3) conducting tests to detect various types of allergies or intolerances in order to base a diet on those results does not appear to be effective. Of these 3 conclusions, the most impressive data that came out of the research was the evidence for the low-FODMAP diet. Not only were there more studies on this diet, but the results were fairly consistent and favorable, at least for the short-term management of IBS.”

” We did not find evidence supporting the idea that prebiotics and synbiotics were effective in IBS management… In ­contrast, studies demonstrated that probiotics did improve global gastrointestinal symptoms, as well as the individual symptoms of bloating and flatulence in patients with IBS. However, determining which probiotic is best was difficult”

“Three prosecretory agents are available: linaclotide (Linzess, Allergan/Ironwood Pharmaceuticals), lubiprostone (Amitiza, Takeda), and plecanatide (Trulance, Synergy Pharmaceuticals), with plecanatide being the most recently approved agent. All 3 of these agents had convincing data to support their use in patients with constipation-predominant IBS

My take: In IBS patients, if dietary therapy is recommended, current evidence favors a low FODMAP diet rather than a gluten-free diet.

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near Banff

Image above -Parker Ridge Trail

Low Quality Evidence for IBS Dietary Therapy

A recent systematic review and meta-analysis (J Dionne et al. Am J Gastroenterol 2018; 113: 1290-1300) throws some shade on the effectiveness of dietary therapies for irritable bowel syndrome. Thanks to Ben Gold for this reference. The authors reviewed 1726 citations -only 9 were eligible for systematic review; two RCTs (n=111 participants) with gluten-free diet (GFD) and 7 RCTs (n=397) with low FODMAPs diet.

Key findings:

  • A GFD was associated with reduced global symptoms compared with control interventions (RR=0.42, CI 0.11-1.55) which was not statistically significant.  Thus, there is “insufficient evidence to recommend a GFD to reduce IBS symptoms.”
  • A low FODMAP diet was associated with reduced global symptoms compared with control interventions (RR=0.69, CI 0.54-0.88). The three RCTs with rigorous control diets found the least magnitude of effect. Thus, the overall quality of the data was “very low” according to the GRADE criteria.

Given the limited data supporting dietary therapy for IBS, the authors caution that in those who are placed on a low FODMAPs diet, that after a 2-6 week trial, those who “fail to improve should not continue the diet. ”

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Differential Microbiome Effects of Prebiotics and low FODMAPs

A recent study (J-W Huaman et al. Gastroenterol 2018; 155: 1004-7) examined the effects of a prebiotic (Bimuno) and a low FODMAPs diet for the treatment of functional GI disorders and their effects on the microbiome.

This was a randomized controlled 4-week trial with a 2-week followup period.  Those who received the prebiotic (N=19) received a placebo diet (Mediterranean-type) and those who were randomized to a low FODMAP diet (n=21) were instructed to consume a placebo.  The prebiotic contained beat-galactooligosaccharide.

Key findings:

  • Both groups had significant reduction in GI symptoms, though low FODMAPs was the only treatment helpful for flatulence/borborygmi.
  • The symptom reduction persisted in the prebiotic group for the 2 -week follow-up period, whereas symptoms reappeared immediately in the low FODMAP group.
  • The two treatments had opposite effects on the intestinal microbiota –the prebiotic treatment led to an increase in bifidobacteria and a decrease in Bilophilia wadsworthia.

My take: (borrowed from editorial pg 960-2): This study “may indicate that the effect of the prebiotic is mediated through its effects on gut microbiota composition, whereas the effect of the low FODMAP diets is more related to the meal composition…than to its effects on gut microbiota composition.”

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From two of the missions in San Antonio

 

 

 

 

Chronic Fatigue and Irritable Bowel Syndrome -10 years after Giardia Infection!

A recent study (S Litleskare et al. Clin Gastroenterol Hepatol 2018; 16: 1064-72) involved prospective follow-up of 1252 laboratory-confirmed cases of giardiasis from a 2004 outbreak in Norway.

Key findings:

  • Prevalence of irritable bowel syndrome (IBS) was 43% 10 years after the outbreak among 576 exposed individuals compared with 14% among 685 controls. Thus, the odds ration of developing IBS was 4.74 following Giardia exposure.
  • Chronic fatigue at 10 years was higher as well, reported in 26% in the exposed group compared with 11% in the control group.
  • The authors note that the change in IBS between 6 years and 10 years following the infection was 40% and 43% respectively and the change in chronic fatigue was 31% at 6 years and 26% at 10 years.

My take: Don’t get Giardia!! It may cause chronic fatigue and IBS 10 years after acquisition of an infection.  This study reinforces other studies which have shown that numerous enteric pathogens can increase the risk of IBS.  These other studies reported lower rates of IBS following infections, between 7-36%.

Moraine Lake, Banff

Why Did the Young Woman’s Heartburn Keep Getting Worse?

Mystery NY Times Case: Why Did the Young Woman’s Heartburn Keep Getting Worse?

An excerpt:

The radiologist who read the scan made an interesting observation. In each of the three visits to the E.R., the patient’s blood had been tested. All three tests showed an elevated white-blood-cell count. That could suggest an infection — but in her tests a quarter of those white blood cells were a cell type known as eosinophils, which normally make up only a tiny fraction of the white blood cells in the circulation. ..

When the radiologist saw the elevated level of eosinophils, however, he recalled an unusual and relatively new disorder known as eosinophilic gastroenteritis (EGE). He added this rarity to the list of possible causes of the patient’s abnormal CT findings on his report…

EGE is thought to be an unusual type of allergic reaction to foods. Food exposure triggers the recruitment of eosinophils to the gut, but once they have a toehold, repeated exposure isn’t necessary to keep them there. The disorder was first described in a series of patients in the United States in 1993 but since then has been found to occur throughout the developed world. Because it’s a relatively new disease, and because our understanding of allergy is still emerging, it’s not well understood. As recognition of the disorder expands, so, too, do the number of cases. Patients are usually started on an elimination diet and given steroids to further suppress the immune system. An elimination diet — one in which the foods most frequently linked to allergic reactions, like milk, eggs and wheat, are not consumed — has been shown to be helpful up to 90 percent of the time.

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Gut-Brain Modulators for Functional GI Disorders: Irritable Bowel, Dyspepsia, Functional Heartburn, and Cyclic Vomiting Syndrome

A lengthy report (DA Drossman et al. Gastroenterol 2018; 154: 1140-71) thoroughly reviews the evidence for neuromodulators for functional GI disorders, including Irritable Bowel, Dyspepsia, Functional Heartburn, and Cyclic Vomiting Syndrome.

“Some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6-12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient-provider relationship.”

The report makes specific recommendations for several functional conditions (Table 4).

  • For dyspepsia, the authors recommend categorizing as either postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) as per Rome IV criteria.
  • They state that “Buspirone…may be used for PDS where early satiety, fullness and nausea predominate.”
  • “Mirtazapine is a good treatment option for PDS when there is chronic nausea and vomiting, or weight loss, and it may also help coexisting abdominal pain.”
  • For EPS, “studies mainly support the use of TCAs, either initially or after an unsuccessful response to a proton pump inhibitor.”

Figure 5 outlines general treatment advice:

  • SSRIs -“when anxiety, depression and phobic features are prominent with FGIDs”
  • TCAs -“first-line treatment when pain is dominant in FGIDs”
  • Tetracyclic antidepressant (mirtazapine, mianserin, trazodone) -“treatment of early satiety, nausea/vomiting, weight loss and disturbed sleep”
  • SNRIs (duloxetiine, venlafaxine, desvenlafaxin, milnacipran) -“treatment when pain is dominant in FGIDs or when side effects from TCAs preclude treatment”
  • Augmentation therapies are subsequently delineated including atyipical antipsychotics, pyschological treatments (like cognitive behavioral therapy) and hypnosis

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.