IRRITABLE BOWEL SYNDROME

I. Clinical features: criteria of Manning et al. (BMJ 2:653, 1978; cited in AIM rvw)

1. Continuous or recurrent sx for 3mos or more, viz.:

1. Abdominal pain, relieved with defecation, or ass'd with a change in freq. or consistency of stool

AND/OR

2. Irregular or varying sx 25% or more of the time including 3 or more of the following:

1. Altered stool frequency
2. Altered stool consistency
3. Altered stool passage (straining or urgency, feeling of incomplete evacuation)
4. Passage of mucus
5. Bloating or feeling of abdominal distention

3. Note that psychosocial disturbances NOT found in people with IBS more than general population, though those people with IBS who seek care do have increased incidence of psychosocial problems
4. Note that most pts continue to have sx years after the original diagnosis

II. Pathophysiology/putative mechanisms

1. Altered motility
2. Abnormal visceral perception
3. Psychological distress
4. Luminal factors causing sx (lactose and other sugars, food allergens, bile acid malabsorption)

III. Initial workup (proposed)

1. CBC and serum chemistries
2. ESR
3. Stool for occult blood
4. Stool for O & P
5. Flex sig
6. Barium enema if > 40yo or family h/o of polyps or colon Ca
7. Some recc. bx to detect colitis in pts with diarrhea or melanosis coli in pts with constipation
8. Psychological/psychiatric screening of some sort
9. Detailed dietary hx with atttention to what precipitates sx, esp. lactose, fructose, sorbitol
10. Hx of use of drugs that might produce GI sx
11. Consider possibility of Celiac Disease

IV. Treatment

1. All pts:

1. Eliminating possible provocative foods then re-introducing after sx resolved
2. Psychotherapy or hypnotherapy may be appropriate

2. Pts with diarrhea as most prominent sx

• Loperamide
• Anticholinergic antidepresants, e.g. desipramine 50 Q8h
• Calcium channel blockers
• 16 pts w/GERD randomized to baclofen 10mg QID vs. placebo x 4wks; Baclofen group had sig. lower sx scores at 4wks (Gut 52:464, 2003--abst)
• If intractable, consider repeating stool O & P and doing jejunal aspirate O & P and maybe SB and colonic transit studies; also can check for bile-acid malabsorption (tx would be cholestyramine) with selenium-75 homocholic acid taurine test

3. Pts with mostly pain-gas-bloating

1. Some recommend avoiding gas-forming foods like legumes, lactose, and fructose, though little evidence of benefit exists
2. Antispasmodics may help (e.g. dicyclomine 10-20mg before meals; peppermint oil; hyoscyamine)
3. Riaximin (Xifaxan), a non-absorbable oral antibiotic, for bloating associated with IBS
   1. Rationale is that many pts with IBS have small-intestinal bacterial overgrowth
   2. In a study in 87 pts with IBS randomized to rifaximin 400mg TID vs. placebo x 10d, riaximin pts had sig. greater improvement in sx scores than placebo pts (Ann. Int. Med. 145:557, 2006--JW)
4. If intractable, consider barium SBFT examination to exclude SB mucosal disease

4. Pts with mostly constipation

1. Bulk-forming laxatives

5. Antidepressants
   1. Tricyclics (see above)
   2. SSRIs
      1. In a randomized trial in 81 pts with IBS randomized to Paroxetine (10mg/d titratable up to 40mg/d) vs. placebo x 12wks, sig. improvement was seen in 63% of pts on paroxetine vs. 26% of placebo recipients (sig.) (Am. J. Gastroent. 99:914, 2004--AFP) 

6. Alosetron (Lotronex)--
   1. A serotonin-type 3-receptor antagonist which has been ass'd with sig. decrease in pain and discomfort c/w placebo in pre-marketing trials
   2. 647 women with IBS (either w/diarrhea or alternating bowel function) randomized to alosetron BID vs. placebo x 12wks. Sig. more alosetron pts (41% vs. 29%) had symptomatic improvement, but also sig. more likely to have problems w/constipation (30% vs. 3%) (Lancet 355:1035, 2000--JW)
   3. Ass'd with severe constipation, even progressing to ischemic colitis in some cases (FDA Advisory 8/24/2000)
   4. Withdrawn from US market 11/00; reintroduced mid-2002 for use in women only, with severe diarrhea-predominant IBS x 6mos, at a lower recommended dose (1mg QD; may increase to 1mg BID after 4wks)

7. Tegaserod (Zelnorm)
   1. A serotonin type-4 agonist; stimulates peristalsis and colonic secretion
   2. See under Constipation for discussion of its use to treat non-IBS constipation
   3. In a randomized trial of 604 men & women 18-65yo with IBS but for whom diarrhea was not a predominant symptom, tegaserod 6mg BID vs. placebo x 12wks was ass'd with significantly higher incidence of symptom relief compared w/placebo at 12wks (34% vs. 23%) (Scand. J. Gastroent. 39:119, 2004--AFP)
   4. In a study in 1,264 adults with chronic constipation (86% women) randomized to tegaserod 2mg or 6mg BID vs. placebo x 12wks, response rate (1 or more complete spontaneous bowel movements per week during first 4wks of tx) was sig. higher in both dose groups of tegaserod recipients vs. placebo (36-40% vs. 27%) but at 12wks, no sig. diff. between 2mg and placebo groups (Am. J. Gastroent. 100:3622, 2005--JW)

8. Antibiotics
   1. Rifaximin (a non-absorbable antibiotic)
      1. In a study in 87 pts 18-65yo with irritable bowel syndrome randomized to Rixafimin 400mg TID vs. placebo, over 7d, rifaximin had sig. more improvement in symptom scores (Ann. Int. Med. 145:557, 2006--JW)
9. Probiotics-Data are mixed as to efficacy
   1. 60 pts with IBS randomized to Lacrobacillus plantarum vs. placebo x 4wks; intervention group was sig. more likely to have 50% decrease in flatulence (44% vs. 18%); nonsig. diff. in likelihood of decrease of abd. pain in intervention group (36% vs. 18%); mean "overall GI function" score sig. more improved in intervention group (Am. J. Gastroent. 95:1231, 2000--JW)
   2. In a study in 64 children 6-20yo with IBS randomized to Lactobacillus GG BID vs. placebo x 6wks; there were no sig. differences in sx during the study period (J. Peds. 147:197, 2005--JW)

9. Peppermint (Mentha piperita)
   1. One standard formulation: Colpermin, Tillotts Pharma--Dose is 187mg 3-4x/d
   2. May cause burning with defecation
   3. May cause GERD sx; enteric-coated form may be less likely to do this
   4. Ass'd with better sx improvement than placebo in a meta-analysis of 5 randomized trials (Am. J. Gastroent. 93:1131, 1998--cited in FP News 2/1/2003 p. 22)

10. Systematic review of 70 published studies on pharmacologic tx of IS found the following:
    1. Bulking agents--Only 4/13 trials showed benefit; mainly in constipation sx; no diff. in abdominal pain or bloating
    2. Muscle relaxants--13/16 showed improvement in pain
    3. Prokinetic agents--2/6 trials showed benefit
    4. Loperamide--4/4 studies showed improvement in diarrhea but not in pain or bloating
    5. Antidepressants--7/7 trials showed some benefit

(Source: Ann. Int. Med 116:1001, 1992)