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Irritable Bowel Syndrome (IBS) - Part 1

Andrew Buelt, DO and Jake Anderson, MD
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In Part 1 of this two part segment, Jake and Andrew review the diagnosis and subtypes of irritable bowel syndrome, the possible causes of the condition, as well as first line therapies.

 

Pearls:

  • IBS is a clinical diagnosis based on the Rome III or IV criteria that includes the recurrence of abdominal pain for at least 3 days out of the month in the past 3 months associated with relation to defecation, onset associated with frequency of stool and/or change in appearance or form of stool.

  • Testing for Celiac (serology) and IBD (CRP) is a good idea in the initial work-up but you probably don’t need endoscopy, fecal studies or abdominal imaging.

  • The cause of IBS is unknown but there does seem to be some relation to the gut flora and intestinal motility sensitivity.

  • Treatment take home points:

    • 1) eliminate triggers from diet

    • 2) Start with a TCA or SSRI

    • 3) Trial psyllium, peppermint oil, amitriptyline

    • 4) If diarrhea predominant: trial rifaximin

    • 5) If constipation predominant: avoid lactulose and trial GoLytely

 

  • What is IBS? Rome III criteria - the recurrence of abdominal pain/discomfort at least 3 days out of the month in the past 3 months associated with two or more of the following:

    • 1) improvement with defecation

    • 2) onset associated with change in frequency of stool

    • 3) change in appearance or form of stool

  • Updates to the Rome III criteria? The Rome III criteria are commonly used but there are now Rome IV criteria that contain minor tweaks.

    • Rome IV specifically removes discomfort and leaves only recurrent pain.

    • Rome IV also says the pain lasts for at least one day per week in the last 3 months.

    • Rome IV says pain has to be related to defecation

  • What is the sensitivity and specificity for certain exam findings?

    • Abdominal pain - 90%/32%

    • Pain relieved by defecation - 60%/66%

    • Passage of mucous by rectum - 45%/65%

    • Looser stools at onset of pain, more frequent stools at onset of pain, patient reported visible abdominal distension - 39-58%/70%

  • Diagnosis?

    • While the differential can be broad, you want to look out for red flag symptoms like nighttime awakenings from pain, age greater than 60 at onset, family history of bowel or ovarian cancer, family history of IBD, unintended weight loss, rectal bleeding/melena.

    • However, if they don’t have these symptoms and they fit the Rome III/IV criteria, you can stop there.

    • Other testing?

      • Celiac disease - consider serologic testing  because a systematic review of observational studies showed an odds ratio  of 4.3 for  celiac disease for patients meeting criteria for IBS.

      • IBD - consider CRP because if < 0.5, it is associated with less than 1% probability of having IBD (based on analysis of 4 studies with 800 adults). Also consider fecal calprotectin - again, if <40 less than 1% chance of IBD (based on 8 studies looking at over 1000 adults)

      • Fecal Studies - not needed unless red flag symptoms

      • Abdominal imaging - not needed unless red flag symptoms

      • Endoscopy - not needed unless red flag symptoms

  • What causes IBS? We aren’t sure but there are many proposed mechanisms including small intestine bacterial overgrowth, imbalance in microflora, allergies and neurologic/muscular hypersensitivity. More research is pointing to a biological basis of disease.

    • There appears to be risk factors:

      • Acute bacterial enteritis has OR 4.5-5.0 of developing IBS

        • Thabane M et. al. Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2007 Aug 15;26(4):535-44. Review. PMID: 17661757.

      • There appears to be a relation between antibiotic use with number needed to harm of 4-6 for functional bowel symptoms over the following four months after antibiotic use.

        • Maxwell PR et. al. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol. 2002 Jan;97(1):104-8. PMID: 11808932.

      • There are also a number of associated conditions like fibromyalgia, migraines and depression when you look at population studies, However, one study found that psychiatric disorders in young people was not associated with IBS.

        • Talley NJ et. al. The irritable bowel syndrome and psychiatric disorders in the community: is there a link? Am J Gastroenterol. 2001 Apr;96(4):1072-9. PMID: 11316149.

  • Treatment for mixed type (constipation, diarrhea)?

    • Diet: eat regularly, get adequate un-caffeinated fluid intake.

      • The evidence on exclusion diets (including FODMAPS) is mixed.

      • One RCT examined antibody-guided elimination of foods based on IgG levels compared to a sham diet. They found reduction of symptoms of only 38 on a 500-point scale.

        • Atkinson W et. al.  Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459-64. PMID: 15361495.

    • Fiber:

      • Insoluble fiber like vegetables might help constipation but worsens other IBS symptoms.

      • Soluble fiber (psyllium) may improve symptoms (weak recommendation by the American College of Gastroenterology, based on 14 trials of 900 patients with NNT of 7 to improve symptoms). This effect seems to wane over time.

        • Moayyedi P et. al. The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2014 Sep;109(9):1367-74. PMID: 25070054.

        • RCT in 2009 comparing psyllium to bran or placebo showed NNT waned from 2 to 6 over 3 months.

          • Bijkerk CJ et. al. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ. 2009 Aug 27;339:b3154. PMID: 19713235.

    • Medications: evidence in this area is also weak

      • Placebo: open-label RCT (patients knew they were taking a placebo pill) among 80 adults showed improvement in global symptom score.

        • Kaptchuk TJ et. al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010 Dec 22;5(12):e15591. PMID: 21203519.

      • Antidepressants: both SSRIs and TCA’s have the highest quality evidence for treatments in IBS.

        • SSRIs: Systematic review in 2014 of 7 RCTs showed NNT 3 to 7 for symptom reduction with 32% reduction in symptoms compared to placebo.

        • TCA: Same review of 11 RCTs including 750 patients comparing placebo to TCA’s found NNT of 4 to 8 with less side effects than SSRIs.

          • Ford AC et. al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2014 Sep;109(9):1350-65. PMID: 24935275.

  • Treatment for diarrhea-predominant IBS?

    • Antispasmodics: Cochrane review in 2011 looking at 29 trials comparing antispasmodics to placebo found NNT of 4 to 11 and higher rates of improvement in global assessment.

      • Most effective was dicyclomine (Bentyl) at 20mg four times a day.

      • Enteric coated peppermint oil capsules 187mg to 325mg three times a day are also among the most effective.

        • Ruepert L et. al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011 Aug 10;(8) PMID: 21833945.

      • The major side effects to worry about are anticholinergic effects but recent review in 2012 showed no difference in adverse effects as compared to placebo.

        • Shah E et. al.. Evaluation of harm in the pharmacotherapy of irritable bowel syndrome. Am J Med. 2012 Apr;125(4):381-93. PMID: 22444104.

    • Loperamide is NOT recommended. Though it seems to help with diarrhea it does not improve overall symptoms.

    • Eluxadoline (Viberzi): FDA approved 2015, mixed opioid activity in the gut. The two industry-sponsored RCTs showed questionable efficacy. It is taken twice a day and costs about $1000 per month. It can’t be taken by those with a history of severe constipation, pancreatitis, biliary duct obstruction, liver impairment, or those who drink three or more alcoholic beverages daily.

      • Lembo AJ. Eluxadoline for Irritable Bowel Syndrome with Diarrhea. N Engl J Med. 2016 Jan 21;374(3):242-53. PMID: 26789872.

    • Rifaximin: Best evidence comes from 2012 systematic review of five RCTs including 1800 patients that showed NNT of 10-11. Follow-up was only 3 to 12 weeks with no difference in adverse effects. It is taken as 550 mg tablet three times a day. It costs about $1300 for the two week treatment. You can repeat two more times.

      • Menees SB et. al. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2012 Jan;107(1):28-35; PMID: 22045120.

    • Alosetron (Lotronex): FDA approved for IBS with diarrhea only in women. Like ondansetron, its a 5-HT receptor blocker. Systematic review of 8 trials including 5000 patients found NNT of 8 for global improvement in IBS symptoms and abdominal pain. Side effect is ischemic colitis. Prescribers have to register with Risk Evaluation and Mitigation Strategy (REMS), following a specific protocol.

      • Ford AC et. al. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; PMID: 19471254.

    • Ondansetron: A 2014 RCT including 120 patients showed NNT of 2 for global symptoms with ondansetron 8mg three times daily. Not FDA approved for this use.

  • Treatment for constipation-predominant IBS?

    • Avoid lactulose.

    • Polyethylene glycol -  no evidence it improves symptoms.

    • NuLytley (GoLytley with electrolytes) has been shown to improve the number of weekly bowel movements. A bottle runs about $10-20.

    • Linaclotide (Linzess): FDA approved for IBS constipation and chronic idiopathic constipation. A 2013 review of 7 RCTs comparing it to placebo showed significant improvement in overall symptoms with NNT of 7. It costs $300 per month for once daily 290mcg.

    • Lubiprostone (Amitiza): FDA approved for IBS with constipation in women over age 18. Taken 8mcg twice daily, a dose much lower than its other use for opioid-induced constipation. Weakest effectiveness with NNT of 13. Costs around $300 per month.

  • Non-medication options:

    • Acupuncture: 2012 Cochrane review of 17 RCTs which included 114 patients comparing acupuncture to sham acupuncture. None of them found actual acupuncture to be any better.

    • CBT: Nine trials comparing CBT to control therapy found a NNT of 3 for overall symptom improvement.

  • Take home points:

    • 1) eliminate triggers from diet

    • 2) Start with a TCA or SSRI

    • 3) Trial psyllium, peppermint oil, amitriptyline

    • 4) If diarrhea predominant: trial rifaximin

    • 5) If constipation predominant: avoid lactulose and trial GoLytely

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