Tag Archives: bile-acid induced diarrhea

Irritable Bowel Syndrome (part 2)

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A terrific 12 page review of irritable bowel syndrome (IBS): AC Ford, BE Lacy, NJ Talley. NEJM 2017; 376: 2566-78. While yesterday’s post reviewed some of the updated diagnostic and pathophysiology information, today’s will focus on treatment.

The article’s Table 2 outlines the most frequent treatments, their efficacy, side effects, costs, and quality of evidence. I’ve tried to highlight the key points from table and discussion:

  1. Soluble fiber (eg. psyllium). Efficacy: effective -start at low doses. Quality of evidence: Moderate, Cost: $15-30 per month.
  2. Low-FODMAP diet. Efficacy: “May be effective, nutritionist guidance helpful.” While there have been studies showing this diet can be effective, two studies have shown that this diet is not significantly superior to conventional IBS diets (eg. “eating small, regular meals and avoiding insoluble fiber, fatty foods, and caffeine”).Quality of evidence: Very low.
  3. Gluten-free diet.  Efficacy: May be effective.  “No additive effect over that of a low-FODMAP diet in another small RCT.” Quality of evidence: Very low.
  4. Antispasmodic drugs (eg. dicyclomine).Efficacy: May be effective. Quality of evidence: Low, “No high-quality trials.” Cost: $50 per month.
  5. Peppermint oil. Efficacy: Effective, though few RCTs and no FDA-approved end points. Quality of evidence: Moderate. “No high-quality trials.”  Cost: $9-19 per month
  6. Lubiprostone. Efficacy: Effective, though “only a modest benefit over placebo, particularly for abdominal pain.” Quality of evidence: Moderate. Cost: ~$350 per month.
  7. Linaclotide.  Efficacy: Effective.. ” Quality of evidence: High. “No high-quality trials.”  Cost: ~$350 per month.
  8. Alosetron/5-HT3 receptor antagonists.  Efficacy: Effective. ” Quality of evidence: High. “No high-quality trials.”  Cost: ~$350-1100 per month. Alosetron may trigger ischemic colitis.
  9. Eluxadoline.  Efficacy: Effective, though “only a modest benefit over placebo for global symptoms and no benefit over placebo for abdominal pain.”  Quality of evidence: High. “No high-quality trials.”  Cost: ~$1100 per month. May trigger pancreatitis.
  10. Rifaximin. Efficacy: Effective. Quality of evidence: Moderate. “Modest benefit over placebo.”  “Relapse among patients who have a response is usual.” Cost: ~$1500 per month.
  11. Probiotics. Efficacy: May be effective.  Quality of evidence: Low. “Few high-quality trials and no FDA-approved end points.”  Cost: ~$20 per month.
  12. Tricyclic antidepressants. Efficacy: Effective. Quality of evidence: Moderate.  “Few high-quality trials and no FDA-approved end points.”   “A meta-analysis showed that tricyclic antidepressants were more effective than placebo in 11 randomized trials involving a total of 744 patients.” Cost: ~$5-10 per month.
  13. Psychological treatments. Efficacy: Effective. Quality of evidence: Low.  “Few high-quality trials and no FDA-approved end points.” “Their efficacy may be overestimated because of the lack of blinding.” There is also difficulty for many patients in finding an appropriate provider.  Cost: ??
  14. Placebo. In treatment trials, a placebo response is noted in 30-40%.
  15. Complementary/Alternative Therapies.  “Herbal therapies remain unclear.  STW5 (Iberogast) has been tested and “showed superiority over placebo.” Melatonin “has been reported to reduce abdominal pain in patients with IBS.”

The authors recommend judicious testing  “Any reassurance derived from colonoscopy to rule out organic disease in patients with IBS is short-lived.”

The authors outline their typical approach.  “Reassurance, explanation, and a positive diagnosis are essential steps in management. We recommend starting with dietary modification (slowly increasing soluble fiber if the patient has IBS with constipation or instituting a low-FODMAP diet temporarily  if the patient has IBS with diarrhea or the mixed subtype of IBS). We also recommend increased exercise and stress reduction.  A probiotic may be added, especially if bloating is prominent.  Pain may be ameliorated with an antispasmodic agent or a tricyclic antidepressant, diarrhea with loperamide or a bile acid sequestrant (eg. colestipol) and constipation with polyethylene glycol.” The other therapies may be used in those with persistent IBS symptoms.

My take: When a disease has this many treatments, usually this means that none of the treatments are all that great.

Related blog posts:

Chattahoochee River

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.

Irritable Bowel Syndrome 2017 (part 1)

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A terrific 12 page review of irritable bowel syndrome (IBS): AC Ford, BE Lacy, NJ Talley. NEJM 2017; 376: 2566-78.

Diagnosis of Irritable Bowel:

Testing: National guidelines recommend that for a patient who meets Rome IV criteria, “the physician should make a positive diagnosis of IBS without resorting to a battery of tests.” Nevertheless, many physicians obtain some workup.  If a workup is undertaken, the authors state “consider limited testing (CBC, CRP level, celiac serological test, fecal calprotectin level)”

Rome IV criteria of IBS are reviewed in Table 1 and includes warning signs.  Summary of Rome IV critieria from emedicine website on Irritable Bowel Syndrome: The Rome IV criteria for the diagnosis of irritable bowel syndrome require that patients have had recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with 2 or more of the following [2]:

  • Related to defecation (may be increased or unchanged by defecation)
  • Associated with a change in stool frequency
  • Associated with a change in stool form or appearance

The Rome IV criteria (May 2016) only require abdominal pain in defining this condition; “discomfort” is no longer a requirement owing to its nonspecificity, and the recurrent abdominal pain. 

Supporting symptoms include the following:

  • Altered stool frequency
  • Altered stool form
  • Altered stool passage (straining and/or urgency)
  • Mucorrhea
  • Abdominal bloating or subjective distention

Four bowel patterns may be seen with irritable bowel syndrome, and these remain in the Rome IV classification. These patterns include the following:

  • IBS-D (diarrhea predominant)
  • IBS-C (constipation predominant)
  • IBS-M (mixed diarrhea and constipation)
  • IBS-U (unclassified; the symptoms cannot be categorized into one of the above three subtypes)

Symptoms not consistent with irritable bowel syndrome should alert the clinician to the possibility of an organic pathology. Inconsistent symptoms include the following:

  • Onset in middle age or older
  • Acute symptoms (irritable bowel syndrome is defined by chronicity)
  • Progressive symptoms
  • Nocturnal symptoms
  • Anorexia or weight loss
  • Fever
  • Rectal bleeding
  • Painless diarrhea
  • Steatorrhea
  • Gluten intolerance

The authors provide a diagnostic algorithm which is straight-forward.  The caption includes “tenderness is not increased by tensing abdominal wall muscles.”  The inclusion of Carnett’s sign is a useful reminder to consider/exclude muscle wall etiologies.

Another important point is that bile-acid diarrhea occurs in a significant fraction of adults with the diarrhea subtype of IBS, more than 25% of cases in a meta-analysis; thus, a therapeutic trial of a bile acid sequestrant may be useful.

Pathophysiology:

There are likely multiple pathways leading to IBS. In fact, Figure 2 lays out a Brain-Gut pathway as well as a Gut-Brain pathway. In the former, genetic predisposition and environmental factors/CNS alterations, could make one more susceptible to IBS after localized GI inflammation.  In the later, changes in the GI tract induced by infection, inflammation, food antigens, and medications which could alter intestinal permeability and/or microbiome could result in changes in CNS function (eg. new-onset anxiety, depression or somatization).  It is well-recognized that after gastrointestinal infections (bacterial, protozoal, viral), “IBS-type symptoms persist in 10 to 20% of infected patients.”

Image from NEJM twitter feed. It is noted that not all pathophysiological processes shown occur in all patients with IBS or in all IBS subtypes.