Irritable bowel syndrome medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Irritable bowel syndrome}}
{{Irritable bowel syndrome}}
{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{Cherry}}


==Overview==
==Overview==
<ref name="pmid10811333">{{cite journal |vauthors=Nobaek S, Johansson ML, Molin G, Ahrné S, Jeppsson B |title=Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome |journal=Am. J. Gastroenterol. |volume=95 |issue=5 |pages=1231–8 |year=2000 |pmid=10811333 |doi=10.1111/j.1572-0241.2000.02015.x |url=}}</ref>
Irritable bowel syndrome ([[Irritable bowel syndrome|IBS]]) is heterogeneous in its presentation. There are no strict guidelines for the treatment of [[Irritable bowel syndrome|IBS]] and therapy is mostly [[symptom]]-based. All [[Irritable bowel syndrome|IBS]] patients are required to adopt a diet low in [[FODMAP|fermentable oligo-, di-, and monosaccharides and polyols]] ([[FODMAP|FODMAPs]]). A psychiatric referral and regular exercise are considered necessary in all [[Irritable bowel syndrome|IBS]] patients. Pharmacological therapy is adjunctive and only preferred in patients where [[symptoms]] of [[Irritable bowel syndrome|IBS]] are moderate-severe in intensity and markedly impair the quality of life. Pharmacological therapy administered to [[Patient|patients]] is based on the predominant [[symptom]] with [[diarrhea]]-predominant, [[constipation]]-predominant and [[pain]]-predominant sub-types having their own different regimens. New therapies such as herbal medicines, tight-junction modulators, [[Mast cell stabilizer|mast cell stabilizers]], [[acupuncture]], and [[Cognitive-behavioral therapy|mind body therapy]] currently have an uncertain role in the treatment of [[Irritable bowel syndrome|IBS]].


The fact that patients benefit from probiotics shows that the composition of gut microflora determines IBS.  Administration of probiotics alters metabolism and composition of the microflora and decreases flatulence in patients.There is no treatment for [disease name]; the mainstay of therapy is supportive care.
==Medical Therapy==
 
* A multimodal treatment regimen is preferred for Irritable bowel syndrome ([[Irritable bowel syndrome|IBS]]).<ref name="pmid19521341">{{cite journal |vauthors=Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, Talley NJ, Quigley EM |title=An evidence-based position statement on the management of irritable bowel syndrome |journal=Am. J. Gastroenterol. |volume=104 Suppl 1 |issue= |pages=S1–35 |year=2009 |pmid=19521341 |doi=10.1038/ajg.2008.122 |url=}}</ref><ref name="pmid1586090">{{cite journal |vauthors=Drossman DA, Thompson WG |title=The irritable bowel syndrome: review and a graduated multicomponent treatment approach |journal=Ann. Intern. Med. |volume=116 |issue=12 Pt 1 |pages=1009–16 |year=1992 |pmid=1586090 |doi= |url=}}</ref><ref name="pmid25224526">{{cite journal |vauthors=Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S |title=American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome |journal=Gastroenterology |volume=147 |issue=5 |pages=1146–8 |year=2014 |pmid=25224526 |doi=10.1053/j.gastro.2014.09.001 |url=}}</ref><ref name="pmid22071696">{{cite journal |vauthors=Camilleri M |title=Pharmacology of the new treatments for lower gastrointestinal motility disorders and irritable bowel syndrome |journal=Clin. Pharmacol. Ther. |volume=91 |issue=1 |pages=44–59 |year=2012 |pmid=22071696 |doi=10.1038/clpt.2011.261 |url=}}</ref><ref name="pmid11156653">{{cite journal |vauthors=Akehurst R, Kaltenthaler E |title=Treatment of irritable bowel syndrome: a review of randomised controlled trials |journal=Gut |volume=48 |issue=2 |pages=272–82 |year=2001 |pmid=11156653 |pmc=1728206 |doi= |url=}}</ref>
OR
* [[Irritable bowel syndrome|IBS]] is heterogeneous in its presentation, which makes it difficult to treat.<ref name="pmid10896640">{{cite journal |vauthors=Jailwala J, Imperiale TF, Kroenke K |title=Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials |journal=Ann. Intern. Med. |volume=133 |issue=2 |pages=136–47 |year=2000 |pmid=10896640 |doi= |url=}}</ref><ref name="pmid252245262">{{cite journal| author=Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S| title=American gastroenterological association institute guideline on the pharmacological management of irritable bowel syndrome. | journal=Gastroenterology | year= 2014 | volume= 147 | issue= 5 | pages= 1146-8 | pmid=25224526 | doi=10.1053/j.gastro.2014.09.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25224526  }}</ref><ref name="pmid15606387">{{cite journal| author = Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum A | title = Meta-analysis: The treatment of irritable bowel syndrome. | journal = Aliment Pharmacol Ther | volume = 20 | issue = 11-12 | pages = 1253-69 | year = 2004 | id = PMID 15606387}}</ref><ref name="pmid108966402">{{cite journal | author = Jailwala J, Imperiale T, Kroenke K | title = Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. | journal = Ann Intern Med | volume = 133 | issue = 2 | pages = 136-47 | year = 2000 | id = PMID 10896640}}</ref>
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].


OR
==== All subtypes of [[Irritable bowel syndrome|IBS]] ====
* Preferred regimen (1): Dietary measures: Low [[FODMAP]] high fiber diet for six-eight weeks
* Preferred regimen (2): Moderate-severe exercise for 30-60 mins 3-5 days a week for 12 weeks
* Preferred regimen (2): Psychiatric referral in all [[Irritable bowel syndrome|IBS]] patients


Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
==== Diarrhea-predominant IBS ====
* Preferred regimen (1): &nbsp;[[Loperamide]]&nbsp;2 mg 45 minutes prior to a meal, as needed
* Alternative regimen (1): [[Ondansetron]]&nbsp;4 mg for five weeks
* Alternative regimen (2):&nbsp;[[Colesevelam]]&nbsp;1.875 g q12h
* Alternative regimen (3): [[Gluten]] free diet for 2 weeks


OR
==== Constipation-predominant IBS ====
* Preferred regimen (1): [[Psyllium]] half-one tbsp q24h, titrated based on response to [[therapy]]
* Preferred regimen (2):17 g of [[polyethylene glycol]] ([[Polyethylene glycol|PEG]]) powder dissolved in 8 ounces of water q24h, may be titrated upto 34 g daily
* Preferred regimen(3) : [[Lubiprostone]] 8 micrograms q12h for 12weeks
* Preferred regimen (4) :&nbsp;[[Linaclotide]]&nbsp;266 micrograms q24h for 12 weeks
* Alternative regimen (1): Tageserod


Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
==== Pain-predominant IBS: ====
===Diet therapy===
* Preferred regimen (1): [[Dicyclomine]]&nbsp;20 mg po q6h as needed
**Alternative regimen (1): [[Hyoscyamine]]&nbsp;0.125 to 0.25 mg po q6h as needed
* Alternative regimen (2): Sustained release&nbsp;[[hyoscyamine]]&nbsp;0.375 to 0.75 mg po q12 hours as needed
* Preferred regimen (2): [[Amitriptyline]],&nbsp;[[Nortriptyline]], or [[Imipramine]]&nbsp;10 to 25 mg hs as needed
** Alternative regimen (1): [[Desipramine]]&nbsp;12.5 to 25 mg hs as needed


====Low FODMAP diet====
==== Refractory IBS: ====
Low [[FODMAP]] diet may help acording to a [[systematic review]] of [[randomized controlled trial]]s<ref name="pmid25982757">{{cite journal| author=Marsh A, Eslick EM, Eslick GD| title=Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. | journal=Eur J Nutr | year= 2016 | volume= 55 | issue= 3 | pages= 897-906 | pmid=25982757 | doi=10.1007/s00394-015-0922-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25982757  }} </ref> and a more recent trial<ref name="pmid27725652">{{cite journal| author=Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K| title=A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D. | journal=Am J Gastroenterol | year= 2016 | volume=  | issue=  | pages=  | pmid=27725652 | doi=10.1038/ajg.2016.434 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27725652  }} </ref>. Included in the systematic review was a trial that combined low FODMAPs and high [[dietary fiber]].<ref name="pmid24076059">{{cite journal| author=Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG| title=A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. | journal=Gastroenterology | year= 2014 | volume= 146 | issue= 1 | pages= 67-75.e5 | pmid=24076059 | doi=10.1053/j.gastro.2013.09.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24076059  }} </ref>
* Preferred regimen (1): [[Rifaximin]]&nbsp;550 mg q8h for 2 weeks


====High dietary fiber====
=== Dietary measures ===
High [[dietary fiber]], especially soluble fiber (psyllium or ispaghula husks) can help according to a [[systematic review]] of [[randomized controlled trial]]s.<ref name="pmid25070054">{{cite journal| author=Moayyedi P, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR et al.| title=The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis. | journal=Am J Gastroenterol | year= 2014 | volume= 109 | issue= 9 | pages= 1367-74 | pmid=25070054 | doi=10.1038/ajg.2014.195 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25070054  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25402531 Review in: Ann Intern Med. 2014 Nov 18;161(10):JC10] </ref> This result is driven by a large [[randomized controlled trial]] that directly compared soluble and insoluble fiber.<ref name="pmid19713235">{{cite journal| author=Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW| title=Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. | journal=BMJ | year= 2009 | volume= 339 | issue= | pages= b3154 | pmid=19713235 | doi=10.1136/bmj.b3154 | pmc=3272664 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19713235  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083814 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-11] </ref>
* General dietary measures for IBS patients include:<ref name="pmid15708012">{{cite journal |vauthors=Kim YJ, Ban DJ |title=Prevalence of irritable bowel syndrome, influence of lifestyle factors and bowel habits in Korean college students |journal=Int J Nurs Stud |volume=42 |issue=3 |pages=247–54 |year=2005 |pmid=15708012 |doi=10.1016/j.ijnurstu.2004.06.015 |url=}}</ref><ref name="pmid22489905">{{cite journal |vauthors=McKenzie YA, Alder A, Anderson W, Wills A, Goddard L, Gulia P, Jankovich E, Mutch P, Reeves LB, Singer A, Lomer MC |title=British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults |journal=J Hum Nutr Diet |volume=25 |issue=3 |pages=260–74 |year=2012 |pmid=22489905 |doi=10.1111/j.1365-277X.2012.01242.x |url=}}</ref><ref name="pmid18456565">{{cite journal |vauthors=Shepherd SJ, Parker FC, Muir JG, Gibson PR |title=Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence |journal=Clin. Gastroenterol. Hepatol. |volume=6 |issue=7 |pages=765–71 |year=2008 |pmid=18456565 |doi=10.1016/j.cgh.2008.02.058 |url=}}</ref><ref name="pmid20659225">{{cite journal |vauthors=Ong DK, Mitchell SB, Barrett JS, Shepherd SJ, Irving PM, Biesiekierski JR, Smith S, Gibson PR, Muir JG |title=Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome |journal=J. Gastroenterol. Hepatol. |volume=25 |issue=8 |pages=1366–73 |year=2010 |pmid=20659225 |doi=10.1111/j.1440-1746.2010.06370.x |url=}}</ref><ref name="pmid19281859">{{cite journal |vauthors=Austin GL, Dalton CB, Hu Y, Morris CB, Hankins J, Weinland SR, Westman EC, Yancy WS, Drossman DA |title=A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=7 |issue=6 |pages=706–708.e1 |year=2009 |pmid=19281859 |pmc=2693479 |doi=10.1016/j.cgh.2009.02.023 |url=}}</ref><ref name="pmid25903636">{{cite journal |vauthors=Rao SS, Yu S, Fedewa A |title=Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=41 |issue=12 |pages=1256–70 |year=2015 |pmid=25903636 |doi=10.1111/apt.13167 |url=}}</ref><ref name="pmid15361495">{{cite journal |vauthors=Atkinson W, Sheldon TA, Shaath N, Whorwell PJ |title=Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial |journal=Gut |volume=53 |issue=10 |pages=1459–64 |year=2004 |pmid=15361495 |pmc=1774223 |doi=10.1136/gut.2003.037697 |url=}}</ref><ref name="pmid4436161">{{cite journal |vauthors=Briggs A, Yazdany S |title=Resistance of Bacillus spores to combined sporicidal treatments |journal=J. Appl. Bacteriol. |volume=37 |issue=4 |pages=623–31 |year=1974 |pmid=4436161 |doi= |url=}}</ref>
** Careful [[Diet (nutrition)|dietary]] history
** [[Caffeine]] and [[alcohol]] avoidance to decrease [[anxiety]] in patients
** [[Legume]] avoidance to decrease symptoms of [[flatulence]]
** Discouraging skipping of entire meals  
** Avoidance of large meals
** Reduced fat intake
** Elimination diets to help remove the most common dietary allergens<ref name="pmid15862933">{{cite journal |vauthors=Lea R, Whorwell PJ |title=The role of food intolerance in irritable bowel syndrome |journal=Gastroenterol. Clin. North Am. |volume=34 |issue=2 |pages=247–55 |year=2005 |pmid=15862933 |doi=10.1016/j.gtc.2005.02.005 |url=}}</ref><ref name="pmid19099570">{{cite journal |vauthors=Harris LR, Roberts L |title=Treatments for irritable bowel syndrome: patients' attitudes and acceptability |journal=BMC Complement Altern Med |volume=8 |issue= |pages=65 |year=2008 |pmid=19099570 |pmc=2633319 |doi=10.1186/1472-6882-8-65 |url=}}</ref><ref name="pmid19559137">{{cite journal |vauthors=Heizer WD, Southern S, McGovern S |title=The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review |journal=J Am Diet Assoc |volume=109 |issue=7 |pages=1204–14 |year=2009 |pmid=19559137 |doi=10.1016/j.jada.2009.04.012 |url=}}</ref>  
** Judicious water intake for the [[constipation]]-predominant [[Irritable bowel syndrome|IBS]] patients to prevent stool dehydration
** Fiber supplementation
** Scheduled timings&nbsp;for bowel evacuations and ensuring intake of stimulating substances&nbsp;such as coffee prior to the scheduled time
** Individualized dietary recommendations for patients
** Avoidance of [[gluten]] as gluten sensitivity may manifest in a subset of [[Irritable bowel syndrome|IBS]] patients <ref name="pmid21224837">{{cite journal |vauthors=Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR |title=Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial |journal=Am. J. Gastroenterol. |volume=106 |issue=3 |pages=508–14; quiz 515 |year=2011 |pmid=21224837 |doi=10.1038/ajg.2010.487 |url=}}</ref><ref name="pmid23648697">{{cite journal |vauthors=Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR |title=No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates |journal=Gastroenterology |volume=145 |issue=2 |pages=320–8.e1–3 |year=2013 |pmid=23648697 |doi=10.1053/j.gastro.2013.04.051 |url=}}</ref><ref name="pmid23357715">{{cite journal |vauthors=Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, Marietta E, O'Neill J, Carlson P, Lamsam J, Janzow D, Eckert D, Burton D, Zinsmeister AR |title=A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function |journal=Gastroenterology |volume=144 |issue=5 |pages=903–911.e3 |year=2013 |pmid=23357715 |pmc=3633663 |doi=10.1053/j.gastro.2013.01.049 |url=}}</ref><ref name="pmid18006603">{{cite journal |vauthors=Verdu EF, Huang X, Natividad J, Lu J, Blennerhassett PA, David CS, McKay DM, Murray JA |title=Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice |journal=Am. J. Physiol. Gastrointest. Liver Physiol. |volume=294 |issue=1 |pages=G217–25 |year=2008 |pmid=18006603 |doi=10.1152/ajpgi.00225.2007 |url=}}</ref>
Exclusion of gas-producing foods:
* Beans, onions, celery, carrots, raisins, bananas, apricots, prunes, cabbage, onions, brussels sprouts, wheat germ, pretzels, and bagels


===Medical therapy===
* '''Low FODMAP diet:'''
[[Clinical practice guideline]]s by the [[American College of Gastroenterology]] address the treatment of irritable bowel syndrome.<ref name="pmid25224526">{{cite journal| author=Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S| title=American gastroenterological association institute guideline on the pharmacological management of irritable bowel syndrome. | journal=Gastroenterology | year= 2014 | volume= 147 | issue= 5 | pages= 1146-8 | pmid=25224526 | doi=10.1053/j.gastro.2014.09.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25224526 }} </ref>
** A diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) is preferred in [[Irritable bowel syndrome|IBS]] patients.<ref name="pmid34376515">{{cite journal| author=Black CJ, Staudacher HM, Ford AC| title=Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. | journal=Gut | year= 2021 | volume=  | issue=  | pages=  | pmid=34376515 | doi=10.1136/gutjnl-2021-325214 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34376515  }} </ref><ref name="pmid25903636" /><ref name="pmid25982757">{{cite journal| author=Marsh A, Eslick EM, Eslick GD| title=Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. | journal=Eur J Nutr | year= 2016 | volume= 55 | issue= 3 | pages= 897-906 | pmid=25982757 | doi=10.1007/s00394-015-0922-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25982757  }}</ref><ref name="pmid27725652">{{cite journal| author=Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K| title=A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D. | journal=Am J Gastroenterol | year= 2016 | volume=  | issue=  | pages=  | pmid=27725652 | doi=10.1038/ajg.2016.434 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27725652  }}</ref><ref name="pmid240760592">{{cite journal| author=Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG| title=A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. | journal=Gastroenterology | year= 2014 | volume= 146 | issue= 1 | pages= 67-75.e5 | pmid=24076059 | doi=10.1053/j.gastro.2013.09.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24076059  }}</ref>
** [[Education]] consists of: <ref name="pmid20659225" /><ref name="pmid15862933" />
*** Elimination of dietary [[FODMAP|FODMAPs]]  for 6-8 weeks
*** Reintroduction of foods high in [[FODMAP|FODMAPs]] to determine individual tolerance to specific foods
** High [[FODMAP]] foods include: <ref name="pmid23449495">{{cite journal |vauthors=Occhipinti K, Smith JW |title=Irritable bowel syndrome: a review and update |journal=Clin Colon Rectal Surg |volume=25 |issue=1 |pages=46–52 |year=2012 |pmid=23449495 |pmc=3348735 |doi=10.1055/s-0032-1301759 |url=}}</ref><ref name="pmid23588241">{{cite journal |vauthors=Shepherd SJ, Lomer MC, Gibson PR |title=Short-chain carbohydrates and functional gastrointestinal disorders |journal=Am. J. Gastroenterol. |volume=108 |issue=5 |pages=707–17 |year=2013 |pmid=23588241 |doi=10.1038/ajg.2013.96 |url=}}</ref>
*** Honey, mangoes cherries, high-[[fructose]] corn syrup, apples, pears, or [[Oligosaccharide|oligosaccharides]] such as wheat
*** [[Mannitol]], [[sorbitol]], [[fructose]],  [[lactose]], [[Fructan|fructans]],  [[xylitol]], and [[Galactan|galactans]]
*** Sugar-[[Alcohol|alcohols]] such as  [[isomalt]], [[maltitol]], [[erythritol]], [[lactitol]], [[mannitol]] and [[xylitol]]
** High [[FODMAP]] foods are poorly absorbed by the gut and are osmotically active short chain [[Carbohydrate|carbohydrates]].
** Rapid fermentation of high [[FODMAP]] foods results in symptoms of [[Abdominal pain|abdominal discomfort]] and [[flatulence]].<ref name="pmid20659225" /><ref name="pmid23588241" /><ref name="pmid24076059">{{cite journal |vauthors=Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG |title=A diet low in FODMAPs reduces symptoms of irritable bowel syndrome |journal=Gastroenterology |volume=146 |issue=1 |pages=67–75.e5 |year=2014 |pmid=24076059 |doi=10.1053/j.gastro.2013.09.046 |url=}}</ref><ref name="pmid17229899">{{cite journal |vauthors=Drisko J, Bischoff B, Hall M, McCallum R |title=Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics |journal=J Am Coll Nutr |volume=25 |issue=6 |pages=514–22 |year=2006 |pmid=17229899 |doi= |url=}}</ref>
* '''Lactose avoidance''':  
** [[Irritable bowel syndrome|IBS]] patients have more subjective [[lactose intolerance]] complaints ([[flatulence]] and [[diarrhea]]) as compared to other individuals.<ref name="pmid18025745">{{cite journal |vauthors=Saberi-Firoozi M, Khademolhosseini F, Mehrabani D, Yousefi M, Salehi M, Heidary ST |title=Subjective lactose intolerance in apparently healthy adults in southern Iran: Is it related to irritable bowel syndrome? |journal=Indian J Med Sci |volume=61 |issue=11 |pages=591–7 |year=2007 |pmid=18025745 |doi= |url=}}</ref><ref name="pmid17559357">{{cite journal |vauthors=Gupta D, Ghoshal UC, Misra A, Misra A, Choudhuri G, Singh K |title=Lactose intolerance in patients with irritable bowel syndrome from northern India: a case-control study |journal=J. Gastroenterol. Hepatol. |volume=22 |issue=12 |pages=2261–5 |year=2007 |pmid=17559357 |doi=10.1111/j.1440-1746.2007.04986.x |url=}}</ref>
** [[Lactose]] ingestion leads to production of [[hydrogen]] gas.
** [[Bacterial]] [[Fermentation (biochemistry)|fermentation]] of the unabsorbed [[lactose]] causes [[symptoms]] of [[bloating]] and [[distension]].
** [[Lactose intolerance]] can be diagnosed using breath testing.<ref name="pmid12591062">{{cite journal |vauthors=Pimentel M, Chow EJ, Lin HC |title=Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study |journal=Am. J. Gastroenterol. |volume=98 |issue=2 |pages=412–9 |year=2003 |pmid=12591062 |doi=10.1111/j.1572-0241.2003.07234.x |url=}}</ref>
** [[Irritable bowel syndrome|IBS]] patients with [[lactose intolerance]] should be given a [[lactose]]-restricted diet.<ref name="pmid19559137" /><ref name="pmid23246646">{{cite journal |vauthors=Yang J, Deng Y, Chu H, Cong Y, Zhao J, Pohl D, Misselwitz B, Fried M, Dai N, Fox M |title=Prevalence and presentation of lactose intolerance and effects on dairy product intake in healthy subjects and patients with irritable bowel syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=11 |issue=3 |pages=262–268.e1 |year=2013 |pmid=23246646 |doi=10.1016/j.cgh.2012.11.034 |url=}}</ref><ref name="pmid23917444">{{cite journal |vauthors=Zhu Y, Zheng X, Cong Y, Chu H, Fried M, Dai N, Fox M |title=Bloating and distention in irritable bowel syndrome: the role of gas production and visceral sensation after lactose ingestion in a population with lactase deficiency |journal=Am. J. Gastroenterol. |volume=108 |issue=9 |pages=1516–25 |year=2013 |pmid=23917444 |doi=10.1038/ajg.2013.198 |url=}}</ref><ref name="pmid11507359">{{cite journal |vauthors=Böhmer CJ, Tuynman HA |title=The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study |journal=Eur J Gastroenterol Hepatol |volume=13 |issue=8 |pages=941–4 |year=2001 |pmid=11507359 |doi= |url=}}</ref>


====Initial treatments====
* '''Fiber in the diet:'''
Medications may consist of stool softeners and [[laxative]]s in constipation-predominant IBS, and antidiarrheals (e.g., [[opioid]]or opioid [[analog (chemistry)|analog]]s such as [[loperamide]], [[diphenoxylate]] or [[codeine]] in diarrhea-predominant IBS for mild symptoms.<ref name="pmid15846668">{{cite journal | author = Quartero A, Meineche-Schmidt V, Muris J, Rubin G, de Wit N | title = Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome. | journal = Cochrane Database Syst Rev | volume = | issue = | pages = CD003460 | year = | id = PMID 15846668}}</ref><ref name="pmid15606387">{{cite journal| author = Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum A | title = Meta-analysis: The treatment of irritable bowel syndrome. | journal = Aliment Pharmacol Ther | volume = 20 | issue = 11-12 | pages = 1253-69 | year = 2004 | id = PMID 15606387}}</ref><ref name="pmid10896640">{{cite journal | author = Jailwala J, Imperiale T, Kroenke K | title = Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. | journal = Ann Intern Med | volume = 133 | issue = 2 | pages = 136-47 | year = 2000 | id = PMID 10896640}}</ref>
** [[Dietary fiber]] decreases [[symptoms]] of [[bloating]] in [[Irritable bowel syndrome|IBS]] patients.<ref name="pmid19559137" /><ref name="pmid14984370">{{cite journal |vauthors=Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ |title=Systematic review: the role of different types of fibre in the treatment of irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=19 |issue=3 |pages=245–51 |year=2004 |pmid=14984370 |doi= |url=}}</ref><ref name="pmid19008265">{{cite journal |vauthors=Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P |title=Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis |journal=BMJ |volume=337 |issue= |pages=a2313 |year=2008 |pmid=19008265 |pmc=2583392 |doi= |url=}}</ref><ref name="pmid16234045">{{cite journal |vauthors=Levy RL, Linde JA, Feld KA, Crowell MD, Jeffery RW |title=The association of gastrointestinal symptoms with weight, diet, and exercise in weight-loss program participants |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=10 |pages=992–6 |year=2005 |pmid=16234045 |doi= |url=}}</ref><ref name="pmid12738451">{{cite journal |vauthors=Talley NJ |title=Pharmacologic therapy for the irritable bowel syndrome |journal=Am. J. Gastroenterol. |volume=98 |issue=4 |pages=750–8 |year=2003 |pmid=12738451 |doi=10.1111/j.1572-0241.2003.07306.x |url=}}</ref><ref name="pmid7912305">{{cite journal |vauthors=Francis CY, Whorwell PJ |title=Bran and irritable bowel syndrome: time for reappraisal |journal=Lancet |volume=344 |issue=8914 |pages=39–40 |year=1994 |pmid=7912305 |doi= |url=}}</ref>
** Soluble [[Fiber|fibers]] are preferred as compared to insoluble [[Fiber|fibers]] for treating [[symptoms]] of [[constipation]].<ref name="pmid19713235">{{cite journal |vauthors=Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW |title=Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial |journal=BMJ |volume=339 |issue= |pages=b3154 |year=2009 |pmid=19713235 |pmc=3272664 |doi= |url=}}</ref><ref name="pmid25070054">{{cite journal| author=Moayyedi P, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR et al.| title=The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis. | journal=Am J Gastroenterol | year= 2014 | volume= 109 | issue= 9 | pages= 1367-74 | pmid=25070054 | doi=10.1038/ajg.2014.195 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25070054  }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25402531 Review in: Ann Intern Med. 2014 Nov 18;161(10):JC10]</ref><ref name="pmid197132352">{{cite journal| author=Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW| title=Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. | journal=BMJ | year= 2009 | volume= 339 | issue= | pages= b3154 | pmid=19713235 | doi=10.1136/bmj.b3154 | pmc=3272664 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19713235  }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083814 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-11]</ref>


=====Laxatives=====
=== '''Physical activity'''&nbsp;===
{{main|laxative}}
*[[Physical exercise|Exercise]] plays an important role in relieving [[Irritable bowel syndrome|IBS]] symptoms by the following mechanisms :<ref name="pmid15708012" /><ref name="pmid16234045" /><ref name="pmid21206488">{{cite journal |vauthors=Johannesson E, Simrén M, Strid H, Bajor A, Sadik R |title=Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial |journal=Am. J. Gastroenterol. |volume=106 |issue=5 |pages=915–22 |year=2011 |pmid=21206488 |doi=10.1038/ajg.2010.480 |url=}}</ref><ref name="pmid11847862">{{cite journal |vauthors=Lustyk MK, Jarrett ME, Bennett JC, Heitkemper MM |title=Does a physically active lifestyle improve symptoms in women with irritable bowel syndrome? |journal=Gastroenterol Nurs |volume=24 |issue=3 |pages=129–37 |year=2001 |pmid=11847862 |doi= |url=}}</ref><ref name="pmid18461499">{{cite journal |vauthors=Daley AJ, Grimmett C, Roberts L, Wilson S, Fatek M, Roalfe A, Singh S |title=The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial |journal=Int J Sports Med |volume=29 |issue=9 |pages=778–82 |year=2008 |pmid=18461499 |doi=10.1055/s-2008-1038600 |url=}}</ref><ref name="pmid17029608">{{cite journal |vauthors=Villoria A, Serra J, Azpiroz F, Malagelada JR |title=Physical activity and intestinal gas clearance in patients with bloating |journal=Am. J. Gastroenterol. |volume=101 |issue=11 |pages=2552–7 |year=2006 |pmid=17029608 |doi=10.1111/j.1572-0241.2006.00873.x |url=}}</ref><ref name="pmid15077462">{{cite journal |vauthors=Taneja I, Deepak KK, Poojary G, Acharya IN, Pandey RM, Sharma MP |title=Yogic versus conventional treatment in diarrhea-predominant irritable bowel syndrome: a randomized control study |journal=Appl Psychophysiol Biofeedback |volume=29 |issue=1 |pages=19–33 |year=2004 |pmid=15077462 |doi= |url=}}</ref><ref name="pmid17149454">{{cite journal |vauthors=Kuttner L, Chambers CT, Hardial J, Israel DM, Jacobson K, Evans K |title=A randomized trial of yoga for adolescents with irritable bowel syndrome |journal=Pain Res Manag |volume=11 |issue=4 |pages=217–23 |year=2006 |pmid=17149454 |pmc=2673138 |doi= |url=}}</ref>
For patients who do not adequately respond to [[dietary fiber]], osmotic agents such as [[polyethylene glycol]], [[sorbitol]], and [[lactulose]] can help avoid 'cathartic colon' which has been associated with stimulant laxatives.<ref name="pmid9649012">{{cite journal | author = Joo J, Ehrenpreis E, Gonzalez L, Kaye M, Breno S, Wexner S, Zaitman D, Secrest K | title = Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited. | journal = J Clin Gastroenterol | volume = 26 |issue = 4 | pages = 283-6 | year = 1998 | id = PMID 9649012}}</ref> Among the osmotic laxatives, 17 to 26 grams/day of [[polyethylene glycol]] (PEG) has been well studied.
**Reduction of stress
**Protection against [[gastrointestinal]] [[symptom]] aggravation
**Alleviation of [[flatulence]]
**Maintenance of [[gastrointestinal]] function
**Elevation of [[sympathetic]] tone, which is found to be decreased in IBS-[[diarrhea]] patients 


=====Antispasmodics=====
=== Psychological therapy and counseling ===
{{main|antispasmodic}}
* It is necessary to build a good physician patient rapport due to the following reasons:<ref name="pmid1586090" /><ref name="pmid23449495" /><ref name="pmid7992984">{{cite journal |vauthors=Owens DM, Nelson DK, Talley NJ |title=The irritable bowel syndrome: long-term prognosis and the physician-patient interaction |journal=Ann. Intern. Med. |volume=122 |issue=2 |pages=107–12 |year=1995 |pmid=7992984 |doi= |url=}}</ref><ref name="pmid7574225">{{cite journal |vauthors=Drossman DA |title=Diagnosing and treating patients with refractory functional gastrointestinal disorders |journal=Ann. Intern. Med. |volume=123 |issue=9 |pages=688–97 |year=1995 |pmid=7574225 |doi= |url=}}</ref><ref name="pmid12425586">{{cite journal |vauthors=Brandt LJ, Bjorkman D, Fennerty MB, Locke GR, Olden K, Peterson W, Quigley E, Schoenfeld P, Schuster M, Talley N |title=Systematic review on the management of irritable bowel syndrome in North America |journal=Am. J. Gastroenterol. |volume=97 |issue=11 Suppl |pages=S7–26 |year=2002 |pmid=12425586 |doi= |url=}}</ref><ref name="pmid3393032">{{cite journal |vauthors=Stewart AL, Hays RD, Ware JE |title=The MOS short-form general health survey. Reliability and validity in a patient population |journal=Med Care |volume=26 |issue=7 |pages=724–35 |year=1988 |pmid=3393032 |doi= |url=}}</ref><ref name="pmid10982758">{{cite journal |vauthors=Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA |title=The impact of irritable bowel syndrome on health-related quality of life |journal=Gastroenterology |volume=119 |issue=3 |pages=654–60 |year=2000 |pmid=10982758 |doi= |url=}}</ref><ref name="pmid2882351">{{cite journal |vauthors=Harvey RF, Mauad EC, Brown AM |title=Prognosis in the irritable bowel syndrome: a 5-year prospective study |journal=Lancet |volume=1 |issue=8539 |pages=963–5 |year=1987 |pmid=2882351 |doi= |url=}}</ref><ref name="pmid18390493">{{cite journal |vauthors=Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I, Schyner RN, Nam BH, Nguyen LT, Park M, Rivers AL, McManus C, Kokkotou E, Drossman DA, Goldman P, Lembo AJ |title=Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome |journal=BMJ |volume=336 |issue=7651 |pages=999–1003 |year=2008 |pmid=18390493 |pmc=2364862 |doi=10.1136/bmj.39524.439618.25 |url=}}</ref><ref name="pmid9178709">{{cite journal |vauthors=Drossman DA, Whitehead WE, Camilleri M |title=Irritable bowel syndrome: a technical review for practice guideline development |journal=Gastroenterology |volume=112 |issue=6 |pages=2120–37 |year=1997 |pmid=9178709 |doi= |url=}}</ref><ref name="pmid22951548">{{cite journal |vauthors=Ford AC, Talley NJ |title=Irritable bowel syndrome |journal=BMJ |volume=345 |issue= |pages=e5836 |year=2012 |pmid=22951548 |doi= |url=}}</ref><ref name="pmid21735420">{{cite journal |vauthors=Kaminski A, Kamper A, Thaler K, Chapman A, Gartlehner G |title=Antidepressants for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents |journal=Cochrane Database Syst Rev |volume= |issue=7 |pages=CD008013 |year=2011 |pmid=21735420 |doi=10.1002/14651858.CD008013.pub2 |url=}}</ref>
The use of antispasmodic drugs (e.g. [[anticholinergic]]s such as [[hyoscyamine]] or [[dicyclomine]]) may help patients, especially those with cramps or diarrhea. A [[meta-analysis]] by the [[Cochrane Collaboration]] concludes that if 6 patients are treated with antispasmodics, 1 patient will benefit ([[number needed to treat]] = 6).<ref name="pmid15846668" /> Antispasmodics can be divided in two groups: neurotropics and musculotropics. Neurotropics, such as [[atropine]], act at the nerve fibre of the parasympathicus but also affect other nerves and have side effects. Musculotropics such as [[mebeverine]] act directly at the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since this action is not mediated by the autonomic nervous system, the usual anticholinergic side effects are absent. Antispasmodic drugs are also available in combination with [[tranquilizers]] or [[barbiturates]], such as [[chlordiazepoxide]] and [[Donnatal]].  The value of the combination therapies has not been established.
** [[Irritable bowel syndrome|IBS]] has a remarkably high placebo response rate
** Treatment regimens need to be individualized in [[Irritable bowel syndrome|IBS]] patients
** Appropriate goals need to be set with emphasis on the chronic nature of the syndrome
** Patient counseling plays an important role
* The 2009 American College of Gastroenterologists (ACG) states that a [[psychiatric]] referral must be considered in all [[Irritable bowel syndrome|IBS]] patients.
* Patients may be given the following therapies for symptom control:<ref name="pmid19521341" />
** [[Cognitive-behavioral therapy]]
** [[Interpersonal psychotherapy]] 
** Dynamic [[psychotherapy]] 
** [[Hypnotherapy]] 
** [[Antidepressants]]: Selective [[Selective serotonin reuptake inhibitor|serotonin reuptake inhibitors]] ([[Selective serotonin reuptake inhibitor|SSRIs]]) and [[tricyclic antidepressants]] ([[Tricyclic antidepressant|TCAs]])  
** [[Behavior modification]]&nbsp;used in conjunction with [[antidepressants]]<ref name="pmid23205588">{{cite journal |vauthors=Labus J, Gupta A, Gill HK, Posserud I, Mayer M, Raeen H, Bolus R, Simren M, Naliboff BD, Mayer EA |title=Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention |journal=Aliment. Pharmacol. Ther. |volume=37 |issue=3 |pages=304–15 |year=2013 |pmid=23205588 |pmc=3829380 |doi=10.1111/apt.12171 |url=}}</ref> 
** [[Anxiolytics]]&nbsp;
*** Used for short-term (less than two weeks) reduction of acute situational [[anxiety]] in [[Irritable bowel syndrome|IBS]] patients
*** Side effects:
**** [[Benzodiazepine|Benzodiazepines]] may lower pain thresholds by stimulating [[Gamma-aminobutyric acid|gamma aminobutyric acid]] ([[Gamma-aminobutyric acid|GABA]]) receptors, thereby decreasing brain [[serotonin]]  
**** Drug interactions
**** High risk of habituation
**** Rebound [[withdrawal]]  


====Drugs affecting serotonin (5-HT)====
=== Pharmacological therapy ===
Drugs affecting [[serotonin]] (5-HT) in the intestines can help reduce symptoms.<ref name="pmid11755632">{{cite journal | author = Talley N | title = Serotoninergic neuroenteric modulators. | journal = Lancet | volume = 358 | issue = 9298 | pages = 2061-8 | year = 2001 | id = PMID 11755632}}</ref> Serotonin stimulates the gut motility and so agonists can help constipation predominate irritable bowel while antagonists can help diarrhea predominant irritable bowel:
Pharmacological therapy is adjunctive and only preferred in patients where symptoms of [[Irritable bowel syndrome|IBS]] are moderate-severe and impair the quality of life.


=====Agonists=====
'''Chloride channel activators:'''
*[[Tegaserod]], a selective 5-HT4 agonist for IBS-C, is available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. On March 30, 2007, the Food and Drug Administration (FDA) requested that Novartis Pharmaceuticals voluntarily discontinue marketing of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events (heart problems) associated with use of the drug. Novartis agreed to voluntarily suspend marketing of the drug in the United States and in many other countries. On July 27, 2007 the Food and Drug Administration (FDA) approved a limited treatment IND program for Zelnorm in the USA to allow restricted access to the medication for patients in need if no comparable alternative drug or therapy is available to treat the disease. The USA FDA had issued two previous warnings about the serious consequences of Tegaserod. In 2005, Tegaserod was rejected as an IBS medication by the European Union. Tegaserod, marketed as Zelnorm in the United States, was the only agent approved to treat the multiple symptoms of IBS (in women only), including constipation, abdominal pain and bloating. A [[meta-analysis]] by the [[Cochrane Collaboration]] concludes that if 17 patients are treated with typical doses of [[tegaserod]], 1 patient will benefit ([[number needed to treat]] = 17).<ref name="pmid14974049">{{cite journal | author = Evans B, Clark W, Moore D, Whorwell P | title = Tegaserod for the treatment of irritable bowel syndrome. |journal = Cochrane Database Syst Rev | volume = | issue = | pages = CD003960 | year = | id = PMID 14974049}}</ref>
* Mechanism of action:  
*[[Selective serotonin reuptake inhibitor]] [[anti-depressants]] (SSRIs), because of their serotonergic effect, would seem to help IBS, especially patients who are constipation predominant. Initial [[crossover studies]]<ref name="pmid16401691">{{cite journal |author = Tack J, Broekaert D, Fischler B, Oudenhove L, Gevers A, Janssens J | title = A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. | journal = Gut | volume = 55 | issue = 8 | pages = 1095-103 |year = 2006 | id = PMID 16401691}}</ref> and [[randomized controlled trials]]<ref name="pmid16128675">{{cite journal | author = Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R | title = The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. | journal = Aliment Pharmacol Ther |volume = 22 | issue = 5 | pages = 381-5 | year = 2005 | id = PMID 16128675}}</ref><ref name="pmid12557136">{{cite journal | author = Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B | title = The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. | journal = Gastroenterology | volume = 124 | issue = 2 | pages = 303-17 | year = 2003 | id = PMID 12557136}}</ref><ref>{{cite journal | author = Tabas G, Beaves M, Wang J, Friday P, Mardini H, Arnold G | title = Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial. | journal = Am J Gastroenterol | volume = 99 | issue = 5 | pages = 914-20 | year = 2004 | id = PMID 15128360}}</ref> support this role.
** [[Chloride channels|Chloride channel]] activators are used for the [[constipation]]-predominant subtype of [[Irritable bowel syndrome|IBS]] and act by enhancing [[chloride]]-rich [[intestinal]] fluid secretions via [[guanylate cyclase]] activation.<ref name="pmid22951548" /><ref name="pmid28083815">{{cite journal |vauthors=Rey E, Mearin F, Alcedo J, Ciriza C, Delgado-Aros S, Freitas T, Mascarenhas M, Mínguez M, Santos J, Serra J |title=Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report |journal=Adv Ther |volume=34 |issue=3 |pages=587–598 |year=2017 |pmid=28083815 |pmc=5350198 |doi=10.1007/s12325-016-0473-8 |url=}}</ref>  
 
** [[Chloride|Chloride ion]] secretion is accompanied by the passive [[diffusion]] of water and sodium to maintain [[Isotonic|isotonicity]].
=====Antagonists=====
* Examples of [[chloride channel]] activators include:
* [[Alosetron]], a selective 5-HT3 antagonist for IBS-D, which is only available for women in the United States under a restricted access program, due to severe risks of [[adverse drug reaction|side-effect]]s if taken mistakenly by IBS-A or IBS-C sufferers.
* [[Cilansetron]], also a selective 5-HT3 antagonist, is undergoing further clinical studies in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew Cilansetron from the United States regulatory approval process after receiving a "not approvable" action letter from the FDA requesting additional clinical trials.
 
====Secretagogues (for constipation)====
Linaclotide, a guanylate cyclase C agonist, can reduce symptoms according to a [[systematic review]] of trials. <ref name="pmid23644388">{{cite journal| author=Videlock EJ, Cheng V, Cremonini F| title=Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. | journal=Clin Gastroenterol Hepatol | year= 2013 | volume= 11 | issue= 9 | pages= 1084-1092.e3; quiz e68 | pmid=23644388 | doi=10.1016/j.cgh.2013.04.032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23644388  }} </ref>
 
====Other agents====
Anti-depressants include both [[tricyclic antidepressants]] (TCAs) and the newer [[selective serotonin reuptake inhibitors]] (SSRIs). In addition to improving symptoms via treating any co-existing depression, TCAs have anti-cholinergic actions while SSRIs are serotonergic. Thus in theory, TCAs would best treat diarrhea-predominant IBS while SSRIs would best treat constipation-predominant IBS. A [[meta-analysis]] of [[randomized controlled trials]] of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve ([[number needed to treat]] = 3).<ref name="pmid11059442">{{cite journal | author = Jackson J, O'Malley P, Tomkins G, Balden E, Santoro J, Kroenke K | title = Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. | journal = Am J Med | volume = 108 | issue = 1 | pages = 65-72 | year = 2000 | id = PMID}}</ref> A separate [[randomized controlled trial]] found that TCAs are best for patients with diarrhea-predominant IBS.<ref name="pmid12851867">{{cite journal | author = Drossman D, Toner B, Whitehead W, Diamant N, Dalton C, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris C, Blackman C, Hu Y, Jia H, Li J, Koch G, Bangdiwala S | title = Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. |journal = Gastroenterology | volume = 125 | issue = 1 | pages = 19-31 | year = 2003 | id = PMID}}</ref>
 
Recent studies have suggested that [[rifaximin]] can be used as an effective treatment for abdominal bloating and [[flatulence]],<ref name="AmJGastro2006-Sharara">{{cite journal | author=Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I | title=A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence| journal=Am J Gastroenterol | year=2006 | pages=326–33 | volume=101 | issue=2 | id=PMID}}</ref><ref name="pmid17043337">{{cite journal | author = Pimentel M, Park S, Mirocha J, Kane S, Kong Y | title = The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. | journal = Ann Intern Med | volume = 145 | issue = 8 | pages = 557-63 | year = 2006 | id = PMID}}</ref> giving more credibility to the potential role of bacterial overgrowth in some patients with IBS.<ref name="AmJGastro2006-Quigley">{{cite journal | author=Quigley EM | title=Germs, gas and the gut; the evolving role of the enteric flora in IBS | journal=Am J Gastroenterol | year=2006 | pages=334–5 | volume=101 | issue=2 | id=PMID}}</ref>
 
The multi-herbal extract [[Iberogast]] was found to be significantly superior to placebo via both an abdominal pain scale and an IBS symptom score after four weeks of treatment.<ref name="Madisch2004">{{cite journal|journal=Aliment Pharmacol Ther|title=Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial|author=Madisch A, Holtmann G, Plein K, Holz J|year=2004|volume=19|pages=271&ndash;9}}</ref>
 
Enteric coated [[peppermint]] oil capsules has been advocated for IBS symptoms in adults and children;<ref name="AmFamPhysician2005-Hadley">{{cite journal | author=Hadley SK, Gaarder SM | title=Treatment of irritable bowel syndrome |journal=Am Fam Physician | year=2005 | pages=2501–6 | volume=72 | issue=12 | id=PMID}}</ref> however, results from trials have been inconsistent.<ref name="pmid3527248">{{cite journal | author = Nash P, Gould S, Bernardo D | title = Peppermint oil does not relieve the pain of irritable bowel syndrome. | journal = Br J Clin Pract | volume = 40 | issue = 7 | pages = 292-3 | year = 1986 | id = PMID}}</ref><ref name="pmid9430014">{{cite journal | author = Liu J, Chen G, Yeh H, Huang C, Poon S | title = Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. | journal = J Gastroenterol |volume = 32 | issue = 6 | pages = 765-8 | year = 1997 | id = PMID}}</ref>  
 
For severe diarrhea-predominant IBS, more potent [[opioids]] may be used, such as [[codeine]] or [[propoxyphene]]; refractory cases may even be treated with [[paregoric]], or, more rarely, [[laudanum|deodorized tincture of opium]] or [[morphine sulfate]]. The use of opioids remains controversial due to the lack of evidence supporting their benefit and the potential risk of [[tolerance]],[[physical dependence]] and [[addiction]].<ref>{{cite book |title=Principles and Practice of Pain Medicine |last=Warfield|first=Carol A. |coauthors=Zahid H. Bajwa |year=2003 |publisher=McGraw-Hill Professional |isbn=0071443495 }}</ref>
 
[[Cannabis]] has theoretical support for its role,<ref name="pmid16133420">{{cite journal | author = Massa F, Storr M, Lutz B | title = The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. | journal = J Mol Med | volume = 83 | issue = 12 | pages = 944-54 | year = 2005 | id = PMID}}</ref><ref name="pmid15159679">{{cite journal | author = Russo E | title = Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? | journal = Neuro Endocrinol Lett | volume = 25 | issue = 1-2 |pages = 31-9 | year = | id = PMID}}</ref> but has not been subject of clinical studies. Although illegal in many counties, it has been prescribed to patients in nations such as [[Canada]]. Some of the argued benefits of cannabis are the reduction of pain and nausea, appetite stimulation, and assisting in falling asleep.
 
==Medical Therapy==
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Disease Name===


* '''1 Stage 1 - Name of stage'''
*[[Linaclotide]] (Linzess) <ref name="pmid22986440">{{cite journal |vauthors=Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, Shi K, MacDougall JE, Shao JZ, Eng P, Fox SM, Schneier HA, Kurtz CB, Johnston JM |title=A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation |journal=Am. J. Gastroenterol. |volume=107 |issue=11 |pages=1714–24; quiz p.1725 |year=2012 |pmid=22986440 |pmc=3504311 |doi=10.1038/ajg.2012.255 |url=}}</ref><ref name="pmid22986437">{{cite journal |vauthors=Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, MacDougall JE, Jia XD, Shao JZ, Fitch DA, Baird MJ, Schneier HA, Johnston JM |title=Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety |journal=Am. J. Gastroenterol. |volume=107 |issue=11 |pages=1702–12 |year=2012 |pmid=22986437 |doi=10.1038/ajg.2012.254 |url=}}</ref>
** 1.1 '''Specific Organ system involved 1'''
*[[Lubiprostone]] (Amitiza)<ref name="pmid22951548">{{cite journal |vauthors=Ford AC, Talley NJ |title=Irritable bowel syndrome |journal=BMJ |volume=345 |issue= |pages=e5836 |year=2012 |pmid=22951548 |doi= |url=}}</ref><ref name="pmid19006537">{{cite journal |vauthors=Drossman DA, Chey WD, Johanson JF, Fass R, Scott C, Panas R, Ueno R |title=Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies |journal=Aliment. Pharmacol. Ther. |volume=29 |issue=3 |pages=329–41 |year=2009 |pmid=19006537 |doi=10.1111/j.1365-2036.2008.03881.x |url=}}</ref><ref name="pmid23644388">{{cite journal| author=Videlock EJ, Cheng V, Cremonini F| title=Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. | journal=Clin Gastroenterol Hepatol | year= 2013 | volume= 11 | issue= 9 | pages= 1084-1092.e3; quiz e68 | pmid=23644388 | doi=10.1016/j.cgh.2013.04.032 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23644388 }}</ref>
*** 1.1.1 '''Adult'''
*Most common side effect: [[Diarrhea]]<ref name="pmid22951548" />
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. '<nowiki/>'''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h(maximum, 100 mg per dose)
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 1.2 '''Specific Organ system involved 2'''
*** 1.2.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 1.2.2 '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
'''5-hydroxytryptamine (serotonin) 3 receptor antagonists:'''
** 2.1 '''Specific Organ system involved 1 '''
* 5-hydroxytryptamine-3 receptor ([[Serotonin|5HT-3]]) antagonists are useful in patients with severe refractory [[diarrhea]]-predominant [[Irritable bowel syndrome|IBS]].'''<ref name="pmid17241888">{{cite journal |vauthors=Gershon MD, Tack J |title=The serotonin signaling system: from basic understanding to drug development for functional GI disorders |journal=Gastroenterology |volume=132 |issue=1 |pages=397–414 |year=2007 |pmid=17241888 |doi=10.1053/j.gastro.2006.11.002 |url=}}</ref><ref name="pmid7720476">{{cite journal |vauthors=Zighelboim J, Talley NJ, Phillips SF, Harmsen WS, Zinsmeister AR |title=Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism |journal=Dig. Dis. Sci. |volume=40 |issue=4 |pages=819–27 |year=1995 |pmid=7720476 |doi= |url=}}</ref><ref name="pmid8387353">{{cite journal |vauthors=Prior A, Read NW |title=Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=7 |issue=2 |pages=175–80 |year=1993 |pmid=8387353 |doi= |url=}}'''
**: '''Note (1):'''  
* The [[enteric]] [[neurons]] of the [[gastrointestinal tract]] bear [[5-HT3 receptor|5-HT3 receptors]].
**: '''Note (2)''':
* Stimulation of [[5-HT3 receptor|5-HT3 receptors]] causes [[intestinal]] hyperactivity and hypersensitivity.
**: '''Note (3):'''
* [[Alosetron]] (Lotronex): 5-hydroxytryptamine-3 receptor ([[Serotonin|5HT-3]]) [[antagonist]]'''
*** 2.1.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.1.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '<nowiki/>'''''(Contraindications/specific instructions)''''''
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
** 2.2 '''Other Organ system involved 2'''
**: '''Note (1):'''
**: '''Note (2):'''
**: '''Note (3):'''
*** 2.2.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)


==References==
==References==
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Latest revision as of 19:16, 28 August 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

Irritable bowel syndrome (IBS) is heterogeneous in its presentation. There are no strict guidelines for the treatment of IBS and therapy is mostly symptom-based. All IBS patients are required to adopt a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). A psychiatric referral and regular exercise are considered necessary in all IBS patients. Pharmacological therapy is adjunctive and only preferred in patients where symptoms of IBS are moderate-severe in intensity and markedly impair the quality of life. Pharmacological therapy administered to patients is based on the predominant symptom with diarrhea-predominant, constipation-predominant and pain-predominant sub-types having their own different regimens. New therapies such as herbal medicines, tight-junction modulators, mast cell stabilizers, acupuncture, and mind body therapy currently have an uncertain role in the treatment of IBS.

Medical Therapy

  • A multimodal treatment regimen is preferred for Irritable bowel syndrome (IBS).[1][2][3][4][5]
  • IBS is heterogeneous in its presentation, which makes it difficult to treat.[6][7][8][9]

All subtypes of IBS

  • Preferred regimen (1): Dietary measures: Low FODMAP high fiber diet for six-eight weeks
  • Preferred regimen (2): Moderate-severe exercise for 30-60 mins 3-5 days a week for 12 weeks
  • Preferred regimen (2): Psychiatric referral in all IBS patients

Diarrhea-predominant IBS

  • Preferred regimen (1):  Loperamide 2 mg 45 minutes prior to a meal, as needed
  • Alternative regimen (1): Ondansetron 4 mg for five weeks
  • Alternative regimen (2): Colesevelam 1.875 g q12h
  • Alternative regimen (3): Gluten free diet for 2 weeks

Constipation-predominant IBS

  • Preferred regimen (1): Psyllium half-one tbsp q24h, titrated based on response to therapy
  • Preferred regimen (2):17 g of polyethylene glycol (PEG) powder dissolved in 8 ounces of water q24h, may be titrated upto 34 g daily
  • Preferred regimen(3) : Lubiprostone 8 micrograms q12h for 12weeks
  • Preferred regimen (4) : Linaclotide 266 micrograms q24h for 12 weeks
  • Alternative regimen (1): Tageserod

Pain-predominant IBS:

Refractory IBS:

  • Preferred regimen (1): Rifaximin 550 mg q8h for 2 weeks

Dietary measures

  • General dietary measures for IBS patients include:[10][11][12][13][14][15][16][17]
    • Careful dietary history
    • Caffeine and alcohol avoidance to decrease anxiety in patients
    • Legume avoidance to decrease symptoms of flatulence
    • Discouraging skipping of entire meals
    • Avoidance of large meals
    • Reduced fat intake
    • Elimination diets to help remove the most common dietary allergens[18][19][20]
    • Judicious water intake for the constipation-predominant IBS patients to prevent stool dehydration
    • Fiber supplementation
    • Scheduled timings for bowel evacuations and ensuring intake of stimulating substances such as coffee prior to the scheduled time
    • Individualized dietary recommendations for patients
    • Avoidance of gluten as gluten sensitivity may manifest in a subset of IBS patients [21][22][23][24]

Exclusion of gas-producing foods:

  • Beans, onions, celery, carrots, raisins, bananas, apricots, prunes, cabbage, onions, brussels sprouts, wheat germ, pretzels, and bagels

Physical activity 

Psychological therapy and counseling

Pharmacological therapy

Pharmacological therapy is adjunctive and only preferred in patients where symptoms of IBS are moderate-severe and impair the quality of life.

Chloride channel activators:

5-hydroxytryptamine (serotonin) 3 receptor antagonists:

  • 5-hydroxytryptamine-3 receptor (5HT-3) antagonists are useful in patients with severe refractory diarrhea-predominant IBS.[69][70]<ref name="pmid8387353">Prior A, Read NW (1993). "Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome". Aliment. Pharmacol. Ther. 7 (2): 175–80. PMID 8387353.
  • The enteric neurons of the gastrointestinal tract bear 5-HT3 receptors.
  • Stimulation of 5-HT3 receptors causes intestinal hyperactivity and hypersensitivity.
  • Alosetron (Lotronex): 5-hydroxytryptamine-3 receptor (5HT-3) antagonist

References

  1. 1.0 1.1 Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, Talley NJ, Quigley EM (2009). "An evidence-based position statement on the management of irritable bowel syndrome". Am. J. Gastroenterol. 104 Suppl 1: S1–35. doi:10.1038/ajg.2008.122. PMID 19521341.
  2. 2.0 2.1 Drossman DA, Thompson WG (1992). "The irritable bowel syndrome: review and a graduated multicomponent treatment approach". Ann. Intern. Med. 116 (12 Pt 1): 1009–16. PMID 1586090.
  3. Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S (2014). "American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome". Gastroenterology. 147 (5): 1146–8. doi:10.1053/j.gastro.2014.09.001. PMID 25224526.
  4. Camilleri M (2012). "Pharmacology of the new treatments for lower gastrointestinal motility disorders and irritable bowel syndrome". Clin. Pharmacol. Ther. 91 (1): 44–59. doi:10.1038/clpt.2011.261. PMID 22071696.
  5. Akehurst R, Kaltenthaler E (2001). "Treatment of irritable bowel syndrome: a review of randomised controlled trials". Gut. 48 (2): 272–82. PMC 1728206. PMID 11156653.
  6. Jailwala J, Imperiale TF, Kroenke K (2000). "Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials". Ann. Intern. Med. 133 (2): 136–47. PMID 10896640.
  7. Weinberg DS, Smalley W, Heidelbaugh JJ, Sultan S (2014). "American gastroenterological association institute guideline on the pharmacological management of irritable bowel syndrome". Gastroenterology. 147 (5): 1146–8. doi:10.1053/j.gastro.2014.09.001. PMID 25224526.
  8. Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum A (2004). "Meta-analysis: The treatment of irritable bowel syndrome". Aliment Pharmacol Ther. 20 (11–12): 1253–69. PMID 15606387.
  9. Jailwala J, Imperiale T, Kroenke K (2000). "Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials". Ann Intern Med. 133 (2): 136–47. PMID 10896640.
  10. 10.0 10.1 Kim YJ, Ban DJ (2005). "Prevalence of irritable bowel syndrome, influence of lifestyle factors and bowel habits in Korean college students". Int J Nurs Stud. 42 (3): 247–54. doi:10.1016/j.ijnurstu.2004.06.015. PMID 15708012.
  11. McKenzie YA, Alder A, Anderson W, Wills A, Goddard L, Gulia P, Jankovich E, Mutch P, Reeves LB, Singer A, Lomer MC (2012). "British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults". J Hum Nutr Diet. 25 (3): 260–74. doi:10.1111/j.1365-277X.2012.01242.x. PMID 22489905.
  12. Shepherd SJ, Parker FC, Muir JG, Gibson PR (2008). "Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence". Clin. Gastroenterol. Hepatol. 6 (7): 765–71. doi:10.1016/j.cgh.2008.02.058. PMID 18456565.
  13. 13.0 13.1 13.2 Ong DK, Mitchell SB, Barrett JS, Shepherd SJ, Irving PM, Biesiekierski JR, Smith S, Gibson PR, Muir JG (2010). "Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome". J. Gastroenterol. Hepatol. 25 (8): 1366–73. doi:10.1111/j.1440-1746.2010.06370.x. PMID 20659225.
  14. Austin GL, Dalton CB, Hu Y, Morris CB, Hankins J, Weinland SR, Westman EC, Yancy WS, Drossman DA (2009). "A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome". Clin. Gastroenterol. Hepatol. 7 (6): 706–708.e1. doi:10.1016/j.cgh.2009.02.023. PMC 2693479. PMID 19281859.
  15. 15.0 15.1 Rao SS, Yu S, Fedewa A (2015). "Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome". Aliment. Pharmacol. Ther. 41 (12): 1256–70. doi:10.1111/apt.13167. PMID 25903636.
  16. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ (2004). "Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial". Gut. 53 (10): 1459–64. doi:10.1136/gut.2003.037697. PMC 1774223. PMID 15361495.
  17. Briggs A, Yazdany S (1974). "Resistance of Bacillus spores to combined sporicidal treatments". J. Appl. Bacteriol. 37 (4): 623–31. PMID 4436161.
  18. 18.0 18.1 Lea R, Whorwell PJ (2005). "The role of food intolerance in irritable bowel syndrome". Gastroenterol. Clin. North Am. 34 (2): 247–55. doi:10.1016/j.gtc.2005.02.005. PMID 15862933.
  19. Harris LR, Roberts L (2008). "Treatments for irritable bowel syndrome: patients' attitudes and acceptability". BMC Complement Altern Med. 8: 65. doi:10.1186/1472-6882-8-65. PMC 2633319. PMID 19099570.
  20. 20.0 20.1 20.2 Heizer WD, Southern S, McGovern S (2009). "The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review". J Am Diet Assoc. 109 (7): 1204–14. doi:10.1016/j.jada.2009.04.012. PMID 19559137.
  21. Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR (2011). "Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial". Am. J. Gastroenterol. 106 (3): 508–14, quiz 515. doi:10.1038/ajg.2010.487. PMID 21224837.
  22. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR (2013). "No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates". Gastroenterology. 145 (2): 320–8.e1–3. doi:10.1053/j.gastro.2013.04.051. PMID 23648697.
  23. Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, Marietta E, O'Neill J, Carlson P, Lamsam J, Janzow D, Eckert D, Burton D, Zinsmeister AR (2013). "A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function". Gastroenterology. 144 (5): 903–911.e3. doi:10.1053/j.gastro.2013.01.049. PMC 3633663. PMID 23357715.
  24. Verdu EF, Huang X, Natividad J, Lu J, Blennerhassett PA, David CS, McKay DM, Murray JA (2008). "Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice". Am. J. Physiol. Gastrointest. Liver Physiol. 294 (1): G217–25. doi:10.1152/ajpgi.00225.2007. PMID 18006603.
  25. Black CJ, Staudacher HM, Ford AC (2021). "Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis". Gut. doi:10.1136/gutjnl-2021-325214. PMID 34376515 Check |pmid= value (help).
  26. Marsh A, Eslick EM, Eslick GD (2016). "Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis". Eur J Nutr. 55 (3): 897–906. doi:10.1007/s00394-015-0922-1. PMID 25982757.
  27. Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K (2016). "A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D". Am J Gastroenterol. doi:10.1038/ajg.2016.434. PMID 27725652.
  28. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG (2014). "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome". Gastroenterology. 146 (1): 67–75.e5. doi:10.1053/j.gastro.2013.09.046. PMID 24076059.
  29. 29.0 29.1 Occhipinti K, Smith JW (2012). "Irritable bowel syndrome: a review and update". Clin Colon Rectal Surg. 25 (1): 46–52. doi:10.1055/s-0032-1301759. PMC 3348735. PMID 23449495.
  30. 30.0 30.1 Shepherd SJ, Lomer MC, Gibson PR (2013). "Short-chain carbohydrates and functional gastrointestinal disorders". Am. J. Gastroenterol. 108 (5): 707–17. doi:10.1038/ajg.2013.96. PMID 23588241.
  31. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG (2014). "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome". Gastroenterology. 146 (1): 67–75.e5. doi:10.1053/j.gastro.2013.09.046. PMID 24076059.
  32. Drisko J, Bischoff B, Hall M, McCallum R (2006). "Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics". J Am Coll Nutr. 25 (6): 514–22. PMID 17229899.
  33. Saberi-Firoozi M, Khademolhosseini F, Mehrabani D, Yousefi M, Salehi M, Heidary ST (2007). "Subjective lactose intolerance in apparently healthy adults in southern Iran: Is it related to irritable bowel syndrome?". Indian J Med Sci. 61 (11): 591–7. PMID 18025745.
  34. Gupta D, Ghoshal UC, Misra A, Misra A, Choudhuri G, Singh K (2007). "Lactose intolerance in patients with irritable bowel syndrome from northern India: a case-control study". J. Gastroenterol. Hepatol. 22 (12): 2261–5. doi:10.1111/j.1440-1746.2007.04986.x. PMID 17559357.
  35. Pimentel M, Chow EJ, Lin HC (2003). "Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study". Am. J. Gastroenterol. 98 (2): 412–9. doi:10.1111/j.1572-0241.2003.07234.x. PMID 12591062.
  36. Yang J, Deng Y, Chu H, Cong Y, Zhao J, Pohl D, Misselwitz B, Fried M, Dai N, Fox M (2013). "Prevalence and presentation of lactose intolerance and effects on dairy product intake in healthy subjects and patients with irritable bowel syndrome". Clin. Gastroenterol. Hepatol. 11 (3): 262–268.e1. doi:10.1016/j.cgh.2012.11.034. PMID 23246646.
  37. Zhu Y, Zheng X, Cong Y, Chu H, Fried M, Dai N, Fox M (2013). "Bloating and distention in irritable bowel syndrome: the role of gas production and visceral sensation after lactose ingestion in a population with lactase deficiency". Am. J. Gastroenterol. 108 (9): 1516–25. doi:10.1038/ajg.2013.198. PMID 23917444.
  38. Böhmer CJ, Tuynman HA (2001). "The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study". Eur J Gastroenterol Hepatol. 13 (8): 941–4. PMID 11507359.
  39. Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ (2004). "Systematic review: the role of different types of fibre in the treatment of irritable bowel syndrome". Aliment. Pharmacol. Ther. 19 (3): 245–51. PMID 14984370.
  40. Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P (2008). "Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis". BMJ. 337: a2313. PMC 2583392. PMID 19008265.
  41. 41.0 41.1 Levy RL, Linde JA, Feld KA, Crowell MD, Jeffery RW (2005). "The association of gastrointestinal symptoms with weight, diet, and exercise in weight-loss program participants". Clin. Gastroenterol. Hepatol. 3 (10): 992–6. PMID 16234045.
  42. Talley NJ (2003). "Pharmacologic therapy for the irritable bowel syndrome". Am. J. Gastroenterol. 98 (4): 750–8. doi:10.1111/j.1572-0241.2003.07306.x. PMID 12738451.
  43. Francis CY, Whorwell PJ (1994). "Bran and irritable bowel syndrome: time for reappraisal". Lancet. 344 (8914): 39–40. PMID 7912305.
  44. Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW (2009). "Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial". BMJ. 339: b3154. PMC 3272664. PMID 19713235.
  45. Moayyedi P, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR; et al. (2014). "The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis". Am J Gastroenterol. 109 (9): 1367–74. doi:10.1038/ajg.2014.195. PMID 25070054. Review in: Ann Intern Med. 2014 Nov 18;161(10):JC10
  46. Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW (2009). "Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial". BMJ. 339: b3154. doi:10.1136/bmj.b3154. PMC 3272664. PMID 19713235. Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-11
  47. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R (2011). "Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial". Am. J. Gastroenterol. 106 (5): 915–22. doi:10.1038/ajg.2010.480. PMID 21206488.
  48. Lustyk MK, Jarrett ME, Bennett JC, Heitkemper MM (2001). "Does a physically active lifestyle improve symptoms in women with irritable bowel syndrome?". Gastroenterol Nurs. 24 (3): 129–37. PMID 11847862.
  49. Daley AJ, Grimmett C, Roberts L, Wilson S, Fatek M, Roalfe A, Singh S (2008). "The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial". Int J Sports Med. 29 (9): 778–82. doi:10.1055/s-2008-1038600. PMID 18461499.
  50. Villoria A, Serra J, Azpiroz F, Malagelada JR (2006). "Physical activity and intestinal gas clearance in patients with bloating". Am. J. Gastroenterol. 101 (11): 2552–7. doi:10.1111/j.1572-0241.2006.00873.x. PMID 17029608.
  51. Taneja I, Deepak KK, Poojary G, Acharya IN, Pandey RM, Sharma MP (2004). "Yogic versus conventional treatment in diarrhea-predominant irritable bowel syndrome: a randomized control study". Appl Psychophysiol Biofeedback. 29 (1): 19–33. PMID 15077462.
  52. Kuttner L, Chambers CT, Hardial J, Israel DM, Jacobson K, Evans K (2006). "A randomized trial of yoga for adolescents with irritable bowel syndrome". Pain Res Manag. 11 (4): 217–23. PMC 2673138. PMID 17149454.
  53. Owens DM, Nelson DK, Talley NJ (1995). "The irritable bowel syndrome: long-term prognosis and the physician-patient interaction". Ann. Intern. Med. 122 (2): 107–12. PMID 7992984.
  54. Drossman DA (1995). "Diagnosing and treating patients with refractory functional gastrointestinal disorders". Ann. Intern. Med. 123 (9): 688–97. PMID 7574225.
  55. Brandt LJ, Bjorkman D, Fennerty MB, Locke GR, Olden K, Peterson W, Quigley E, Schoenfeld P, Schuster M, Talley N (2002). "Systematic review on the management of irritable bowel syndrome in North America". Am. J. Gastroenterol. 97 (11 Suppl): S7–26. PMID 12425586.
  56. Stewart AL, Hays RD, Ware JE (1988). "The MOS short-form general health survey. Reliability and validity in a patient population". Med Care. 26 (7): 724–35. PMID 3393032.
  57. Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA (2000). "The impact of irritable bowel syndrome on health-related quality of life". Gastroenterology. 119 (3): 654–60. PMID 10982758.
  58. Harvey RF, Mauad EC, Brown AM (1987). "Prognosis in the irritable bowel syndrome: a 5-year prospective study". Lancet. 1 (8539): 963–5. PMID 2882351.
  59. Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I, Schyner RN, Nam BH, Nguyen LT, Park M, Rivers AL, McManus C, Kokkotou E, Drossman DA, Goldman P, Lembo AJ (2008). "Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome". BMJ. 336 (7651): 999–1003. doi:10.1136/bmj.39524.439618.25. PMC 2364862. PMID 18390493.
  60. Drossman DA, Whitehead WE, Camilleri M (1997). "Irritable bowel syndrome: a technical review for practice guideline development". Gastroenterology. 112 (6): 2120–37. PMID 9178709.
  61. 61.0 61.1 61.2 61.3 Ford AC, Talley NJ (2012). "Irritable bowel syndrome". BMJ. 345: e5836. PMID 22951548.
  62. Kaminski A, Kamper A, Thaler K, Chapman A, Gartlehner G (2011). "Antidepressants for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents". Cochrane Database Syst Rev (7): CD008013. doi:10.1002/14651858.CD008013.pub2. PMID 21735420.
  63. Labus J, Gupta A, Gill HK, Posserud I, Mayer M, Raeen H, Bolus R, Simren M, Naliboff BD, Mayer EA (2013). "Randomised clinical trial: symptoms of the irritable bowel syndrome are improved by a psycho-education group intervention". Aliment. Pharmacol. Ther. 37 (3): 304–15. doi:10.1111/apt.12171. PMC 3829380. PMID 23205588.
  64. Rey E, Mearin F, Alcedo J, Ciriza C, Delgado-Aros S, Freitas T, Mascarenhas M, Mínguez M, Santos J, Serra J (2017). "Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report". Adv Ther. 34 (3): 587–598. doi:10.1007/s12325-016-0473-8. PMC 5350198. PMID 28083815.
  65. Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, Shi K, MacDougall JE, Shao JZ, Eng P, Fox SM, Schneier HA, Kurtz CB, Johnston JM (2012). "A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation". Am. J. Gastroenterol. 107 (11): 1714–24, quiz p.1725. doi:10.1038/ajg.2012.255. PMC 3504311. PMID 22986440.
  66. Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, MacDougall JE, Jia XD, Shao JZ, Fitch DA, Baird MJ, Schneier HA, Johnston JM (2012). "Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety". Am. J. Gastroenterol. 107 (11): 1702–12. doi:10.1038/ajg.2012.254. PMID 22986437.
  67. Drossman DA, Chey WD, Johanson JF, Fass R, Scott C, Panas R, Ueno R (2009). "Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies". Aliment. Pharmacol. Ther. 29 (3): 329–41. doi:10.1111/j.1365-2036.2008.03881.x. PMID 19006537.
  68. Videlock EJ, Cheng V, Cremonini F (2013). "Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis". Clin Gastroenterol Hepatol. 11 (9): 1084–1092.e3, quiz e68. doi:10.1016/j.cgh.2013.04.032. PMID 23644388.
  69. Gershon MD, Tack J (2007). "The serotonin signaling system: from basic understanding to drug development for functional GI disorders". Gastroenterology. 132 (1): 397–414. doi:10.1053/j.gastro.2006.11.002. PMID 17241888.
  70. Zighelboim J, Talley NJ, Phillips SF, Harmsen WS, Zinsmeister AR (1995). "Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism". Dig. Dis. Sci. 40 (4): 819–27. PMID 7720476.

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