Irritable bowel syndrome medical therapy: Difference between revisions

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


==Overview==
==Overview==
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]].


==Medical Therapy==
==Medical Therapy==
===new===
* 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>
Treatment: multimodal<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>
* [[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>


difficulty of treating a syndrome that is heterogeneous in its presentation, a remarkably high placebo response rate. <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="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>
==== All subtypes of [[Irritable bowel syndrome|IBS]] ====
Even though patients’ symptoms overlap, addressing them individually <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>
* Preferred regimen (1): Dietary measures: Low [[FODMAP]] high fiber diet for six-eight weeks
Build patient rapport<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="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="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>
* 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


allows the physician to simplify and organize the appropriate medical therapy.
==== 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


the rela- tionship and rapport between the physician and patient is very important.
==== Constipation-predominant IBS ====
* patient counseling <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="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> <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>
* Preferred regimen (1): [[Psyllium]] half-one tbsp q24h, titrated based on response to [[therapy]]
* more specific individualized treatment and setting of appropriate goals with emphasis on the chronic nature of the syndrome <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>
* 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
* Psychological therapy: use of Antidepressant medications 
* Preferred regimen(3) : [[Lubiprostone]] 8 micrograms q12h for 12weeks
* Caffeine avoidance to decrease anxiety 
* Preferred regimen (4) :&nbsp;[[Linaclotide]]&nbsp;266 micrograms q24h for 12 weeks
* Avoidance of legumes decreases bloating 
* Alternative regimen (1): Tageserod
DIETARY MEASURES
* Fiber supplementation: side effect bloating and distension <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>
* Individualized dietary recommendations are preferable
* Elimination diets remove the most common allergens from the diet
* skipping entire meals worsen IBS symptoms <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>
* Flatulence: Polycarbophil compounds (eg, Citrucel, FiberCon)< than psyllium compounds (eg, Metamucil)  
* Judicious water intake is recommended for the constipation-predominant subtype of IBS
* Avoidance of gluten is advised as gluten sensitivity may manifest in a subset of 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>
* Patients are advised diets low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) <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>
* Probiotics relieve pain, bloating, and flatulence
PSYCHOLOGICAL THERAPY
* The 2009 American College of Gastroenterologists (ACG) state that:
* In all IBS patients, a psychiatric referral must be considered.
* Cognitive-behavioral therapy and interpersonal psychotherapy
* Dynamic psychotherapy, and hypnotherapy
* Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants are effective in the treatment of irritable bowel syndrome
ADJUNCTIVE PHARMACOLOGIC THERAPY
* Agents used for the management of IBS symptoms include:
** Anticholinergics
** Antidiarrheals
** Tricyclic antidepressants
** Prokinetics
** Bulk-forming laxatives <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="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><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>
** Serotonin receptor antagonists
** Chloride channel activators
** Guanylate cyclase C (GC-C) agonists: Linaclotide for the management of the constipation-predominant disease (IBS-C) subtype <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>
** Antispasmodics such as peppermint oil, pinaverium, trimebutine, and cimetropium/dicyclomine <ref name="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref><ref name="pmid17420159">{{cite journal |vauthors=Cappello G, Spezzaferro M, Grossi L, Manzoli L, Marzio L |title=Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial |journal=Dig Liver Dis |volume=39 |issue=6 |pages=530–6 |year=2007 |pmid=17420159 |doi=10.1016/j.dld.2007.02.006 |url=}}</ref><ref name="pmid19277023">{{cite journal |vauthors=Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS |title=The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review |journal=Am. J. Gastroenterol. |volume=104 |issue=4 |pages=1033–49; quiz 1050 |year=2009 |pmid=19277023 |doi=10.1038/ajg.2009.25 |url=}}</ref><ref name="pmid19507027">{{cite journal |vauthors=Merat S, Khalili S, Mostajabi P, Ghorbani A, Ansari R, Malekzadeh R |title=The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome |journal=Dig. Dis. Sci. |volume=55 |issue=5 |pages=1385–90 |year=2010 |pmid=19507027 |doi=10.1007/s10620-009-0854-9 |url=}}</ref>
** Peppermint oil, which has antispasmodic properties by relaxing smooth muscle,  Use: abdominal discomfort  pain and abdominal distention
** Loperamide effectively reduced stool frequency and improved stool consistency <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="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="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="pmid3306904">{{cite journal |vauthors=Hovdenak N |title=Loperamide treatment of the irritable bowel syndrome |journal=Scand. J. Gastroenterol. Suppl. |volume=130 |issue= |pages=81–4 |year=1987 |pmid=3306904 |doi= |url=}}</ref><ref name="pmid8734343">{{cite journal |vauthors=Efskind PS, Bernklev T, Vatn MH |title=A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome |journal=Scand. J. Gastroenterol. |volume=31 |issue=5 |pages=463–8 |year=1996 |pmid=8734343 |doi=10.3109/00365529609006766 |url=}}</ref><ref name="pmid6365490">{{cite journal |vauthors=Cann PA, Read NW, Holdsworth CD, Barends D |title=Role of loperamide and placebo in management of irritable bowel syndrome (IBS) |journal=Dig. Dis. Sci. |volume=29 |issue=3 |pages=239–47 |year=1984 |pmid=6365490 |doi= |url=}}</ref> <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>
** Polyethylene glycol <ref name="pmid25091148">{{cite journal |vauthors=Ford AC, Moayyedi P, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Quigley EM |title=American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation |journal=Am. J. Gastroenterol. |volume=109 Suppl 1 |issue= |pages=S2–26; quiz S27 |year=2014 |pmid=25091148 |doi=10.1038/ajg.2014.187 |url=}}</ref>: polyethylene glycol can be considered for refractory cases as it was shown to improve stool frequency <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>
** Rifaximin (550 mg PO q8h for 14 d) for bloating, abdominal pain, diarrhea <ref name="pmid22045120">{{cite journal |vauthors=Menees SB, Maneerattannaporn M, Kim HM, Chey WD |title=The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis |journal=Am. J. Gastroenterol. |volume=107 |issue=1 |pages=28–35; quiz 36 |year=2012 |pmid=22045120 |doi=10.1038/ajg.2011.355 |url=}}</ref><ref name="pmid21208106">{{cite journal |vauthors=Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP |title=Rifaximin therapy for patients with irritable bowel syndrome without constipation |journal=N. Engl. J. Med. |volume=364 |issue=1 |pages=22–32 |year=2011 |pmid=21208106 |doi=10.1056/NEJMoa1004409 |url=}}</ref><ref name="pmid24486051">{{cite journal |vauthors=Shanahan F, Quigley EM |title=Manipulation of the microbiota for treatment of IBS and IBD-challenges and controversies |journal=Gastroenterology |volume=146 |issue=6 |pages=1554–63 |year=2014 |pmid=24486051 |doi=10.1053/j.gastro.2014.01.050 |url=}}</ref>
'''Constipation-predominant symptoms'''


Linaclotide and lubiprostone enhance chloride-rich intestinal fluid secretions without altering sodium and potassium concentrations in the serum.
==== Pain-predominant IBS: ====
*Lubiprostone (Amitiza) <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="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>
* Preferred regimen (1): [[Dicyclomine]]&nbsp;20 mg po q6h as needed
** MOA: activates chloride channels in the apical part of the small bowel epithelium. As a result, chloride ions are secreted and sodium and water passively diffuse into the lumen to maintain isotonicity.<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>
**Alternative regimen (1): [[Hyoscyamine]]&nbsp;0.125 to 0.25 mg po q6h as needed
*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><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>
* Alternative regimen (2): Sustained release&nbsp;[[hyoscyamine]]&nbsp;0.375 to 0.75 mg po q12 hours as needed
**Guanylate cyclase agonist; activates chloride channels in intestinal epithelial cells to increase intestinal fluid secretion
* 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


'''Diarrhea-predominant IBS'''
==== Refractory IBS: ====
*Alosetron (Lotronex): Alosetron is a 5-HT3 receptor antagonist.
* Preferred regimen (1): [[Rifaximin]]&nbsp;550 mg q8h for 2 weeks
**5-HT3 receptors are located on the enteric neurons of the GI tract, and stimulation causes hypersensitivity and hyperactivity of the intestine.
*Eluxadoline (Viberzi): Eluxadoline is a mu opioid receptor agonist, delta opioid receptor antagonist, and a kappa opioid receptor agonist.


'''Anticholinergics'''
=== Dietary measures ===
*MOA: inhibit intestinal smooth-muscle depolarization at the muscarinic receptor, relieving  symptoms of intestinal spasms in irritable bowel syndrome
* 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>
**Dicyclomine hydrochloride (Bentyl)   
** Careful [[Diet (nutrition)|dietary]] history
**MOA: blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS, decreasing fecal urgency and pain.
** [[Caffeine]] and [[alcohol]] avoidance to decrease [[anxiety]] in patients
**Hyoscyamine sulfate (Levsin) 
** [[Legume]] avoidance to decrease symptoms of [[flatulence]]
**MOA: blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects, decreases fecal urgency and pain.  
** Discouraging skipping of entire meals  
'''Antidiarrheals''' 
** Avoidance of large meals
*MOA: nonabsorbable synthetic opioids.
** Reduced fat intake
**They prolong the GI transit time
** 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>
**decrease secretion via peripheral µ-opioid receptors
** Judicious water intake for the [[constipation]]-predominant [[Irritable bowel syndrome|IBS]] patients to prevent stool dehydration
**reduce visceral nociception via afferent pathway inhibition
** 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


*Diphenoxylate hydrochloride 2.5 mg with atropine sulfate 0.025 mg (Lomotil)  
* '''Low FODMAP diet:'''
** 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>


*Diphenoxylate is a constipating meperidine congener and 0.025 mg of atropine discourages abuse.  
* '''Fiber in the diet:'''
*MOA: inhibits excessive GI propulsion and motility, but it may exacerbate constipation.  
** [[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>


*Loperamide (Imodium)
=== '''Physical activity'''&nbsp;===
**MOA: acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility 
*[[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>
**prolongs the movement of electrolytes and fluid through bowel 
**Reduction of stress
**increases the viscosity and loss of fluids and electrolytes 
**Protection against [[gastrointestinal]] [[symptom]] aggravation
**Loperamide improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation
**Alleviation of [[flatulence]]
**MOA:  increase gastrointestinal transit time by interacting with the GI musculature, thus allowing for more water absorption  Side effects: used with extreme caution because  severe constipation
**Maintenance of [[gastrointestinal]] function
addiction potential.
**Elevation of [[sympathetic]] tone, which is found to be decreased in IBS-[[diarrhea]] patients 
*Tricyclic Antidepressants: <ref name="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref><ref name="pmid7821126">{{cite journal |vauthors=Gorard DA, Libby GW, Farthing MJ |title=Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome |journal=Dig. Dis. Sci. |volume=40 |issue=1 |pages=86–95 |year=1995 |pmid=7821126 |doi= |url=}}</ref><ref name="pmid19001059">{{cite journal |vauthors=Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P |title=Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis |journal=Gut |volume=58 |issue=3 |pages=367–78 |year=2009 |pmid=19001059 |doi=10.1136/gut.2008.163162 |url=}}</ref><ref name="pmid7821126">{{cite journal |vauthors=Gorard DA, Libby GW, Farthing MJ |title=Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome |journal=Dig. Dis. Sci. |volume=40 |issue=1 |pages=86–95 |year=1995 |pmid=7821126 |doi= |url=}}</ref><ref name="pmid7986966">{{cite journal |vauthors=Clouse RE, Lustman PJ, Geisman RA, Alpers DH |title=Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience |journal=Aliment. Pharmacol. Ther. |volume=8 |issue=4 |pages=409–16 |year=1994 |pmid=7986966 |doi= |url=}}</ref><ref name="pmid19001059">{{cite journal |vauthors=Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P |title=Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis |journal=Gut |volume=58 |issue=3 |pages=367–78 |year=2009 |pmid=19001059 |doi=10.1136/gut.2008.163162 |url=}}</ref><ref name="pmid15128360">{{cite journal |vauthors=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 |pmid=15128360 |doi=10.1111/j.1572-0241.2004.04127.x |url=}}</ref><ref name="pmid16401691">{{cite journal |vauthors=Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, 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 |pmid=16401691 |pmc=1856276 |doi=10.1136/gut.2005.077503 |url=}}</ref><ref name="pmid15017494">{{cite journal |vauthors=Kuiken SD, Tytgat GN, Boeckxstaens GE |title=The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study |journal=Clin. Gastroenterol. Hepatol. |volume=1 |issue=3 |pages=219–28 |year=2003 |pmid=15017494 |doi=10.1053/cgh.2003.50032 |url=}}</ref><ref name="pmid16128675">{{cite journal |vauthors=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 |pmid=16128675 |doi=10.1111/j.1365-2036.2005.02566.x |url=}}</ref><ref name="pmid12557136">{{cite journal |vauthors=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 |pmid=12557136 |doi=10.1053/gast.2003.50055 |url=}}</ref><ref name="pmid19765674">{{cite journal |vauthors=Ladabaum U, Sharabidze A, Levin TR, Zhao WK, Chung E, Bacchetti P, Jin C, Grimes B, Pepin CJ |title=Citalopram provides little or no benefit in nondepressed patients with irritable bowel syndrome |journal=Clin. Gastroenterol. Hepatol. |volume=8 |issue=1 |pages=42–48.e1 |year=2010 |pmid=19765674 |pmc=2818161 |doi=10.1016/j.cgh.2009.09.008 |url=}}</ref><ref name="pmid24651166">{{cite journal |vauthors=Bundeff AW, Woodis CB |title=Selective serotonin reuptake inhibitors for the treatment of irritable bowel syndrome |journal=Ann Pharmacother |volume=48 |issue=6 |pages=777–84 |year=2014 |pmid=24651166 |doi=10.1177/1060028014528151 |url=}}</ref><ref name="pmid26252008">{{cite journal |vauthors=Xie C, Tang Y, Wang Y, Yu T, Wang Y, Jiang L, Lin L |title=Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis |journal=PLoS ONE |volume=10 |issue=8 |pages=e0127815 |year=2015 |pmid=26252008 |pmc=4529302 |doi=10.1371/journal.pone.0127815 |url=}}</ref>
imipramine and amitriptyline have both antidepressive and analgesic properties.


MOA:  
=== Psychological therapy and counseling ===
* 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>
** [[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]]


facilitate endogenous endorphin release
=== Pharmacological therapy ===
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.


blockade of norepinephrine leading to enhancement of descending inhibitory pain pathways
'''Chloride channel activators:'''
* Mechanism of action: 
** [[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]].
* Examples of [[chloride channel]] activators include:


blockade of the pain neuromodulator, serotonin
*[[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>
*[[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>
*Most common side effect: [[Diarrhea]]<ref name="pmid22951548" />


TCAs, ''via'' their anticholinergic properties, also slow intestinal transit time, which may provide benefit in diarrhea-predominant IBS
'''5-hydroxytryptamine (serotonin) 3 receptor antagonists:'''
 
* 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=}}'''
reduce the visceral hypersensitivity
* The [[enteric]] [[neurons]] of the [[gastrointestinal tract]] bear [[5-HT3 receptor|5-HT3 receptors]].
 
* Stimulation of [[5-HT3 receptor|5-HT3 receptors]] causes [[intestinal]] hyperactivity and hypersensitivity.
'''side effects''' of constipation and sedation is essential.
* [[Alosetron]] (Lotronex): 5-hydroxytryptamine-3 receptor ([[Serotonin|5HT-3]]) [[antagonist]]'''
**Imipramine (Tofranil)
**increases pain threshold in the gut, thereby providing a visceral analgesic effect. <ref name="pmid9136853">{{cite journal |vauthors=Bueno L, Fioramonti J, Delvaux M, Frexinos J |title=Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations |journal=Gastroenterology |volume=112 |issue=5 |pages=1714–43 |year=1997 |pmid=9136853 |doi= |url=}}</ref>  
**prolongs oral-cecal transit time; reduces abdominal pain, mucorrhea, and stool frequency
 
*Amitriptyline (Elavil) <ref name="pmid19596010">{{cite journal |vauthors=Saps M, Youssef N, Miranda A, Nurko S, Hyman P, Cocjin J, Di Lorenzo C |title=Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders |journal=Gastroenterology |volume=137 |issue=4 |pages=1261–9 |year=2009 |pmid=19596010 |pmc=2827243 |doi=10.1053/j.gastro.2009.06.060 |url=}}</ref><ref name="pmid18410774">{{cite journal |vauthors=Bahar RJ, Collins BS, Steinmetz B, Ament ME |title=Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents |journal=J. Pediatr. |volume=152 |issue=5 |pages=685–9 |year=2008 |pmid=18410774 |doi=10.1016/j.jpeds.2007.10.012 |url=}}</ref>
**MOA: provides a visceral analgesic effect at doses subtherapeutic for antidepressive actions
**prolongs oral-cecal transit time, reduces abdominal pain, mucorrhea, and stool frequency
'''Antibiotics'''
*benefit from treatment appears to be transient.
 
*routine use of antibiotics in all IBS patients is not recommended.  
 
*try a 2-wk trial of rifaximin in those patients with IBS without constipation and with moderate to severe symptoms, especially bloating, who have failed other therapies. 
 
*MOA: prevent the overgrowth of intestinal bacteria
 
Rifaximin (Xifaxan) <ref name="pmid22045120">{{cite journal |vauthors=Menees SB, Maneerattannaporn M, Kim HM, Chey WD |title=The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis |journal=Am. J. Gastroenterol. |volume=107 |issue=1 |pages=28–35; quiz 36 |year=2012 |pmid=22045120 |doi=10.1038/ajg.2011.355 |url=}}</ref><ref name="pmid16454838">{{cite journal |vauthors=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. |volume=101 |issue=2 |pages=326–33 |year=2006 |pmid=16454838 |doi=10.1111/j.1572-0241.2006.00458.x |url=}}</ref>
*Rifaximin is a semisynthetic derivative of rifampin
*MOA: binding to the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking one of the steps in transcription.
*inhibition of bacterial protein synthesis thereby inhibiting bacterial growth
 
'''Bulk-Forming Laxatives''' <ref name="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref>
*Composition: natural and semi-synthetic hydrophilic polysaccharides and cellulose derivatives that form emollient gels in water and facilitate intestinal passage and stimulate peristalsis.
* As fiber supplements, these products improve symptoms of constipation and diarrhea
 
*Methylcellulose (Citrucel)
**MOA: promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.
 
*Psyllium (Metamucil, Fiberall, Reguloid, Konsyl)
**Psyllium promotes bowel evacuation by forming a viscous liquid and promoting peristalsis.
 
'''INITIAL THERAPY''' <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>
 
'''Education and reassurance''' — Patient must be involved in treatment decisions.
 
'''Dietary modification''' — Careful dietary history
 
Traditional IBS diet: <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>
 
Regular meal pattern
 
Avoidance of large meals
 
Reduced intake of fat
 
Insoluble fibers
 
Caffeine
 
Gas-producing foods such as beans, cabbage, and onions
Some food restriction of high FODMAP foods
In select cases, lactose and gluten avoidance<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>  <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>
 
Exclusion of gas-producing foods: Foods that increase flatulence (eg, beans, onions, celery, carrots, raisins, bananas, apricots, prunes, Brussels sprouts, wheat germ, pretzels, and bagels), alcohol, and caffeine
 
'''Lactose avoidance''':<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>
 
Patients with known lactose intolerance should be placed on a lactose-restricted diet.<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>
 
Diagnosis of lactose intolerance can be confirmed with:
 
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>
 
Patients with IBS were found to have  more subjective lactose intolerance complaints (bloating, distention, and diarrhea) than those without IBS
 
MOA: following ingestion of lactose, hydrogen gas is produced and gut distention is promoted due to bacterial fermentation of the unabsorbed lactose.
 
'''Low FODMAP diet''' — a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) in patients with IBS with abdominal bloating or pain
 
These short-chain carbohydrates are poorly absorbed and are osmotically active in the intestinal lumen where they are rapidly fermented, resulting in symptoms of abdominal bloating and pain.<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><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="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>
 
Elimination of a larger number of high FODMAP foods such as foods that contain fructose, including honey, high-fructose corn syrup, apples, pears, mangoes, cherries, or oligosaccharides, including wheat<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>
* FODMAPs table
FODMAPs include fructans, galactans, lactose, fructose, sorbitol,
 
xylitol, and mannitol
 
are poorly absorbed in the GI tract and may cause increased flatulence, abdominal discomfort. <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>
 
sugar-alcohols that aggravate IBS symptoms include :
 
mannitol, xylitol, erythritol, lactitol, maltitol, and isomalt.
 
Low FODMAP education consists of initially eliminating FODMAPs from the diet for six to eight weeks and then, following symptom resolution, gradual reintroduction of foods high in fermentable carbohydrates to determine individual tolerance to specific fermentable carbohydrates <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="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>
 
'''Fiber: FIBER'''<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><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>
 
'''Use: bloating'''<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>
 
'''consumption''' '''of soluble fiber resulted in a decrease in global''' '''IBS symptoms and constipation, whereas insoluble fiber''' '''demonstrated a less significant effect.'''<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>
 
'''Food allergy testing''' — The role of food allergy in IBS is unclear. <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>
 
'''Physical activity''' — potential benefit with regard to IBS symptoms and the general health benefits of exercise <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>
* Exercise relieves symptoms by : <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="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="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="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>
** maintain GI function
** reduce stress
** protects against GI symptom aggravation
** alleviates gas  
** Pranayama yoga increases sympathetic tone, which is decreased in IBS-D <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><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>
 
'''ADJUNCTIVE PHARMACOLOGIC THERAPY''' 
 
'''Constipation''' — 
IBS with constipation (IBS-C) who have failed a trial of soluble fiber (eg, psyllium/ispaghula), we suggest polyethylene glycol (PEG).
treat patients with persistent constipation despite treatment with PEG with lubiprostone or linaclotide. 
* increase  consumption of fiber-enriched foods
 
* fluid intake to prevent stool dehydration
 
* schedule times for bowel evacuations with the aid of stimulating substances such as coffee or prunes allows for a regimental routine
 
*  Bulking agents (corn fiber, bran, psyllium, polycarbophil, ispaghula husk, and methylcellulose)
 
* MOA: increases luminal water, which adds bulk to the stool and allows easier stool passage.
'''Osmotic laxatives'''<ref name="pmid27531591">{{cite journal |vauthors=Gordon M, MacDonald JK, Parker CE, Akobeng AK, Thomas AG |title=Osmotic and stimulant laxatives for the management of childhood constipation |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD009118 |year=2016 |pmid=27531591 |doi=10.1002/14651858.CD009118.pub3 |url=}}</ref> — PEG is inexpensive, widely available, and has fewer side effects as compared with other osmotic laxatives (eg, lactulose, milk of magnesia).<ref name="pmid23835436">{{cite journal |vauthors=Chapman RW, Stanghellini V, Geraint M, Halphen M |title=Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome |journal=Am. J. Gastroenterol. |volume=108 |issue=9 |pages=1508–15 |year=2013 |pmid=23835436 |doi=10.1038/ajg.2013.197 |url=}}</ref><ref name="pmid15269628">{{cite journal |vauthors=Michail S, Gendy E, Preud'Homme D, Mezoff A |title=Polyethylene glycol for constipation in children younger than eighteen months old |journal=J. Pediatr. Gastroenterol. Nutr. |volume=39 |issue=2 |pages=197–9 |year=2004 |pmid=15269628 |doi= |url=}}</ref><ref name="pmid15572895">{{cite journal |vauthors=Loening-Baucke V, Krishna R, Pashankar DS |title=Polyethylene glycol 3350 without electrolytes for the treatment of functional constipation in infants and toddlers |journal=J. Pediatr. Gastroenterol. Nutr. |volume=39 |issue=5 |pages=536–9 |year=2004 |pmid=15572895 |doi= |url=}}</ref><ref name="pmid11930092">{{cite journal |vauthors=Loening-Baucke V |title=Polyethylene glycol without electrolytes for children with constipation and encopresis |journal=J. Pediatr. Gastroenterol. Nutr. |volume=34 |issue=4 |pages=372–7 |year=2002 |pmid=11930092 |doi= |url=}}</ref><ref name="pmid12041718">{{cite journal |vauthors=Gremse DA, Hixon J, Crutchfield A |title=Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children |journal=Clin Pediatr (Phila) |volume=41 |issue=4 |pages=225–9 |year=2002 |pmid=12041718 |doi=10.1177/000992280204100405 |url=}}</ref><ref name="pmid16254521">{{cite journal |vauthors=Dupont C, Leluyer B, Maamri N, Morali A, Joye JP, Fiorini JM, Abdelatif A, Baranes C, Benoît S, Benssoussan A, Boussioux JL, Boyer P, Brunet E, Delorme J, François-Cecchin S, Gottrand F, Grassart M, Hadji S, Kalidjian A, Languepin J, Leissler C, Lejay D, Livon D, Lopez JP, Mougenot JF, Risse JC, Rizk C, Roumaneix D, Schirrer J, Thoron B, Kalach N |title=Double-blind randomized evaluation of clinical and biological tolerance of polyethylene glycol 4000 versus lactulose in constipated children |journal=J. Pediatr. Gastroenterol. Nutr. |volume=41 |issue=5 |pages=625–33 |year=2005 |pmid=16254521 |doi= |url=}}</ref><ref name="pmid17626140">{{cite journal |vauthors=Thomson MA, Jenkins HR, Bisset WM, Heuschkel R, Kalra DS, Green MR, Wilson DC, Geraint M |title=Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study |journal=Arch. Dis. Child. |volume=92 |issue=11 |pages=996–1000 |year=2007 |pmid=17626140 |pmc=2083581 |doi=10.1136/adc.2006.115493 |url=}}</ref><ref name="pmid16882804">{{cite journal |vauthors=Loening-Baucke V, Pashankar DS |title=A randomized, prospective, comparison study of polyethylene glycol 3350 without electrolytes and milk of magnesia for children with constipation and fecal incontinence |journal=Pediatrics |volume=118 |issue=2 |pages=528–35 |year=2006 |pmid=16882804 |doi=10.1542/peds.2006-0220 |url=}}</ref><ref name="pmid22969980">{{cite journal |vauthors=Wang Y, Wang B, Jiang X, Jiang M, Xu C, Shao C, Jia L, Huang Z, Xu X, Liu H, Shang L |title=Polyethylene glycol 4000 treatment for children with constipation: A randomized comparative multicenter study |journal=Exp Ther Med |volume=3 |issue=5 |pages=853–856 |year=2012 |pmid=22969980 |pmc=3438798 |doi=10.3892/etm.2012.491 |url=}}</ref><ref name="pmid23591910">{{cite journal |vauthors=Alper A, Pashankar DS |title=Polyethylene glycol: a game-changer laxative for children |journal=J. Pediatr. Gastroenterol. Nutr. |volume=57 |issue=2 |pages=134–40 |year=2013 |pmid=23591910 |doi=10.1097/MPG.0b013e318296404a |url=}}</ref>
 
'''Lubiprostone''' — Lubiprostone is a locally acting chloride channel activator that enhances chloride-rich intestinal fluid secretion. <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>
 
'''Guanylate cyclase agonists''' — Linaclotide is a guanylate cyclase agonist that stimulates intestinal fluid secretion and transit.
Diarrhea was the most common side effect.<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>
 
'''5-hydroxytryptamine (serotonin) 4 receptor agonists'''  prokinetics or secretagogues for patients with constipation predominant
<ref name="pmid16393297">{{cite journal |vauthors=Khoshoo V, Armstead C, Landry L |title=Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=23 |issue=1 |pages=191–6 |year=2006 |pmid=16393297 |doi=10.1111/j.1365-2036.2006.02705.x |url=}}</ref><ref name="pmid10493276">{{cite journal |vauthors=Scott LJ, Perry CM |title=Tegaserod |journal=Drugs |volume=58 |issue=3 |pages=491–6; discussion 497–8 |year=1999 |pmid=10493276 |doi= |url=}}</ref>
Agonists of the 5-hydroxytryptamine-4 (5-HT4) receptor stimulate the release of neurotransmitters and increase colonic motility.
 
However, the first partial 5-HT4 receptor agonist, tegaserod has cardiovascular side effects.
 
'''Diarrhea''' —
Use antidiarrheals (eg, loperamide) as initial treatment
Use bile acid sequestrants as second-line therapy
 
'''Antidiarrheal agents''' — loperamide 2 mg 45 minutes before a meal on regularly scheduled doses.
Antidiarrheal agents inhibit peristalsis, prolong transit time, and reduce fecal volume.
 
*Eluxadoline is an agent that combines a mu-opioid receptor agonist and a delta-opioid receptor antagonist.<ref name="pmid26092951">{{cite journal |vauthors=Traynor K |title=Eluxadoline approved for irritable bowel syndrome with diarrhea |journal=Am J Health Syst Pharm |volume=72 |issue=13 |pages=1078 |year=2015 |pmid=26092951 |doi=10.2146/news150043 |url=}}</ref><ref name="pmid23583433">{{cite journal |vauthors=Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS |title=Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study |journal=Gastroenterology |volume=145 |issue=2 |pages=329–38.e1 |year=2013 |pmid=23583433 |doi=10.1053/j.gastro.2013.04.006 |url=}}</ref><ref name="pmid26789872">{{cite journal |vauthors=Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS |title=Eluxadoline for Irritable Bowel Syndrome with Diarrhea |journal=N. Engl. J. Med. |volume=374 |issue=3 |pages=242–53 |year=2016 |pmid=26789872 |doi=10.1056/NEJMoa1505180 |url=}}</ref>
Adverse events associated with eluxadoline were nausea, constipation, and abdominal pain. 
 
Pancreatitis developed in a small fraction of patients treated with eluxadoline.
 
'''Bile acid sequestrants''' — 
side effects including bloating, flatulence, abdominal discomfort, and constipation.
50 percent of patients with functional diarrhea and IBS-D have bile acid malabsorption <ref name="pmid19570102">{{cite journal |vauthors=Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ |title=Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=30 |issue=7 |pages=707–17 |year=2009 |pmid=19570102 |doi=10.1111/j.1365-2036.2009.04081.x |url=}}</ref><ref name="pmid17680846">{{cite journal |vauthors=Fernández-Bañares F, Esteve M, Salas A, Alsina M, Farré C, González C, Buxeda M, Forné M, Rosinach M, Espinós JC, Maria Viver J |title=Systematic evaluation of the causes of chronic watery diarrhea with functional characteristics |journal=Am. J. Gastroenterol. |volume=102 |issue=11 |pages=2520–8 |year=2007 |pmid=17680846 |doi=10.1111/j.1572-0241.2007.01438.x |url=}}</ref><ref name="pmid19879973">{{cite journal |vauthors=Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, Lamsam J, Singh R, Zinsmeister AR |title=Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function |journal=Clin. Gastroenterol. Hepatol. |volume=8 |issue=2 |pages=159–65 |year=2010 |pmid=19879973 |pmc=2822105 |doi=10.1016/j.cgh.2009.10.020 |url=}}</ref><ref name="pmid19879973">{{cite journal |vauthors=Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, Lamsam J, Singh R, Zinsmeister AR |title=Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function |journal=Clin. Gastroenterol. Hepatol. |volume=8 |issue=2 |pages=159–65 |year=2010 |pmid=19879973 |pmc=2822105 |doi=10.1016/j.cgh.2009.10.020 |url=}}</ref>
 
Cholestyramine <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>
 
Bile acids cause diarrhea by stimulating colonic secretion and motility.
 
'''5-hydroxytryptamine (serotonin) 3 receptor antagonists'''<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=}}</ref><ref name="pmid12776000">{{cite journal |vauthors=Gershon MD |title=Serotonin and its implication for the management of irritable bowel syndrome |journal=Rev Gastroenterol Disord |volume=3 Suppl 2 |issue= |pages=S25–34 |year=2003 |pmid=12776000 |doi= |url=}}</ref><ref name="pmid24334242">{{cite journal |vauthors=Garsed K, Chernova J, Hastings M, Lam C, Marciani L, Singh G, Henry A, Hall I, Whorwell P, Spiller R |title=A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea |journal=Gut |volume=63 |issue=10 |pages=1617–25 |year=2014 |pmid=24334242 |pmc=4173656 |doi=10.1136/gutjnl-2013-305989 |url=}}</ref><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>
 Alosetron, a 5-hydroxytryptamine-3 receptor (5HT-3) antagonist, for the treatment of severe diarrhea-predominant IBS who have failed to respond to all other conventional treatment. Alosetron modulates visceral afferent activity from the gastrointestinal tract, thereby decreasing colonic motility and secretion, and may improve abdominal pain
Side effects of ischemic colitis and complications of severe constipation <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="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="pmid8359066">{{cite journal |vauthors=Drossman DA, Li Z, Andruzzi E, Temple RD, Talley NJ, Thompson WG, Whitehead WE, Janssens J, Funch-Jensen P, Corazziari E |title=U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact |journal=Dig. Dis. Sci. |volume=38 |issue=9 |pages=1569–80 |year=1993 |pmid=8359066 |doi= |url=}}</ref><ref name="pmid12454866">{{cite journal |vauthors=Drossman DA, Camilleri M, Mayer EA, Whitehead WE |title=AGA technical review on irritable bowel syndrome |journal=Gastroenterology |volume=123 |issue=6 |pages=2108–31 |year=2002 |pmid=12454866 |doi=10.1053/gast.2002.37095 |url=}}</ref>
 
'''Abdominal pain and bloating''' — In patients with abdominal pain due to IBS, we use antispasmodics.
In patients with persistent abdominal pain despite antispasmodics, we recommend a trial of antidepressants.
 
'''Antispasmodic agents''' <ref name="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref><ref name="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref><ref name="pmid11207510">{{cite journal |vauthors=Poynard T, Regimbeau C, Benhamou Y |title=Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=15 |issue=3 |pages=355–61 |year=2001 |pmid=11207510 |doi= |url=}}</ref><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="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>
— Antispasmodic include those that directly affect intestinal smooth muscle relaxation (eg, mebeverine and pinaverine), and those that act via their anticholinergic properties (eg, dicyclomine and hyoscyamine). <ref name="pmid25632806">{{cite journal |vauthors=Zheng L, Lai Y, Lu W, Li B, Fan H, Yan Z, Gong C, Wan X, Wu J, Huang D, Wang Y, Mei Y, Li Z, Jiang Z, Liu X, Ye J, Yang Y, Huang H, Xiao J |title=Pinaverium Reduces Symptoms of Irritable Bowel Syndrome in a Multicenter, Randomized, Controlled Trial |journal=Clin. Gastroenterol. Hepatol. |volume=13 |issue=7 |pages=1285–1292.e1 |year=2015 |pmid=25632806 |doi=10.1016/j.cgh.2015.01.015 |url=}}</ref><ref name="pmid7016973">{{cite journal |vauthors=Page JG, Dirnberger GM |title=Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride) |journal=J. Clin. Gastroenterol. |volume=3 |issue=2 |pages=153–6 |year=1981 |pmid=7016973 |doi= |url=}}</ref><ref name="pmid12454866">{{cite journal |vauthors=Drossman DA, Camilleri M, Mayer EA, Whitehead WE |title=AGA technical review on irritable bowel syndrome |journal=Gastroenterology |volume=123 |issue=6 |pages=2108–31 |year=2002 |pmid=12454866 |doi=10.1053/gast.2002.37095 |url=}}</ref>
*S/E constipation <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>
 
MOA: The selective inhibition of gastrointestinal smooth muscle by antispasmodics and peppermint oil reduce stimulated colonic motor activity and may be beneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency. <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>
 
Typical doses include: 
 
●Dicyclomine 20 mg orally four times daily 
 
●Hyoscyamine 0.125 to 0.25 mg orally or sublingually three to four times daily as needed 
 
●Sustained release hyoscyamine 0.375 to 0.75 mg orally every 12 hours
 
Side effects:
 
constipation
 
dry mouth 
 
visual disturbances
 
urinary retention
 
'''Antidepressants''' — <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="pmid21833945">{{cite journal |vauthors=Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW |title=Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=8 |pages=CD003460 |year=2011 |pmid=21833945 |doi=10.1002/14651858.CD003460.pub3 |url=}}</ref><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="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>
Antidepressants have analgesic properties independent of their mood improving effects. 
 
Tricyclic antidepressants (TCAs), via their anticholinergic properties, also slow intestinal transit time, which may provide benefit in diarrhea-predominant IBS. <ref name="pmid19001059">{{cite journal |vauthors=Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P |title=Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis |journal=Gut |volume=58 |issue=3 |pages=367–78 |year=2009 |pmid=19001059 |doi=10.1136/gut.2008.163162 |url=}}</ref><ref name="pmid7821126">{{cite journal |vauthors=Gorard DA, Libby GW, Farthing MJ |title=Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome |journal=Dig. Dis. Sci. |volume=40 |issue=1 |pages=86–95 |year=1995 |pmid=7821126 |doi= |url=}}</ref><ref name="pmid9136853">{{cite journal |vauthors=Bueno L, Fioramonti J, Delvaux M, Frexinos J |title=Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations |journal=Gastroenterology |volume=112 |issue=5 |pages=1714–43 |year=1997 |pmid=9136853 |doi= |url=}}</ref><ref name="pmid7986966">{{cite journal |vauthors=Clouse RE, Lustman PJ, Geisman RA, Alpers DH |title=Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience |journal=Aliment. Pharmacol. Ther. |volume=8 |issue=4 |pages=409–16 |year=1994 |pmid=7986966 |doi= |url=}}</ref>
 
Due to the delayed onset of action of antidepressants, three to four weeks of therapy should be attempted before increasing the dose. 
 
Amitriptyline, nortriptyline, and imipramine can be started at a dose of 10 to 25 mg at bedtime.
 
Desipramine should be started at a dose of 12.5 to 25 mg at bedtime.
If the patient is intolerant of one TCA, another may be tried.
 
'''Antibiotics''' — In patients with moderate to severe IBS without constipation, particularly those with bloating, who have failed to respond to other therapies (eg, a diet low in fermentable oligo-, di-, and monosaccharides and polyols [FODMAPs], antispasmodics, and TCAs), we suggest a two-week trial of rifaximin. <ref name="pmid17043337">{{cite journal |vauthors=Pimentel M, Park S, Mirocha J, Kane SV, 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 |pmid=17043337 |doi= |url=}}</ref><ref name="pmid21208106">{{cite journal |vauthors=Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP |title=Rifaximin therapy for patients with irritable bowel syndrome without constipation |journal=N. Engl. J. Med. |volume=364 |issue=1 |pages=22–32 |year=2011 |pmid=21208106 |doi=10.1056/NEJMoa1004409 |url=}}</ref><ref name="pmid21208106">{{cite journal |vauthors=Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP |title=Rifaximin therapy for patients with irritable bowel syndrome without constipation |journal=N. Engl. J. Med. |volume=364 |issue=1 |pages=22–32 |year=2011 |pmid=21208106 |doi=10.1056/NEJMoa1004409 |url=}}</ref><ref name="pmid11151884">{{cite journal |vauthors=Pimentel M, Chow EJ, Lin HC |title=Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome |journal=Am. J. Gastroenterol. |volume=95 |issue=12 |pages=3503–6 |year=2000 |pmid=11151884 |doi=10.1111/j.1572-0241.2000.03368.x |url=}}</ref><ref name="pmid21208106">{{cite journal |vauthors=Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP |title=Rifaximin therapy for patients with irritable bowel syndrome without constipation |journal=N. Engl. J. Med. |volume=364 |issue=1 |pages=22–32 |year=2011 |pmid=21208106 |doi=10.1056/NEJMoa1004409 |url=}}</ref>
 
'''Probiotics''' — Probiotics are not routinely recommended in patients with IBS. <ref name="pmid19091823">{{cite journal |vauthors=Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM |title=The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review |journal=Gut |volume=59 |issue=3 |pages=325–32 |year=2010 |pmid=19091823 |doi=10.1136/gut.2008.167270 |url=}}</ref><ref name="pmid12656692">{{cite journal |vauthors=Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, Zinsmeister AR |title=A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=17 |issue=7 |pages=895–904 |year=2003 |pmid=12656692 |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="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="pmid12578506">{{cite journal |vauthors=Spanier JA, Howden CW, Jones MP |title=A systematic review of alternative therapies in the irritable bowel syndrome |journal=Arch. Intern. Med. |volume=163 |issue=3 |pages=265–74 |year=2003 |pmid=12578506 |doi= |url=}}</ref><ref name="pmid19277023">{{cite journal |vauthors=Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS |title=The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review |journal=Am. J. Gastroenterol. |volume=104 |issue=4 |pages=1033–49; quiz 1050 |year=2009 |pmid=19277023 |doi=10.1038/ajg.2009.25 |url=}}</ref><ref name="pmid16441466">{{cite journal |vauthors=Hussain Z, Quigley EM |title=Systematic review: Complementary and alternative medicine in the irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=23 |issue=4 |pages=465–71 |year=2006 |pmid=16441466 |doi=10.1111/j.1365-2036.2006.02776.x |url=}}</ref>
 
 Use: reduce pain, bloating, and defecatory difficulty and to normalize stool habit in IBS patients, regardless of predominant bowel habit.
 
'''REFRACTORY SYMPTOMS''' —presence of alarm features that should prompt further evaluation.
 
'''Behavior modification''' — Patients with unrelenting symptoms that are associated with psychiatric impairment may benefit from behavioral modification 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''' —  '''limited''' to short-term (less than two weeks) reduction of acute situational anxiety that may be contributing to symptoms. Side effects of anxiolytics include the risk of habituation, rebound withdrawal, and drug interactions. Furthermore, benzodiazepines may lower pain thresholds by stimulating gamma aminobutyric acid (GABA) receptors, thereby decreasing brain serotonin. 
 
'''Other therapies''' — <ref name="pmid12578506">{{cite journal |vauthors=Spanier JA, Howden CW, Jones MP |title=A systematic review of alternative therapies in the irritable bowel syndrome |journal=Arch. Intern. Med. |volume=163 |issue=3 |pages=265–74 |year=2003 |pmid=12578506 |doi= |url=}}</ref><ref name="pmid16437473">{{cite journal |vauthors=Liu JP, Yang M, Liu YX, Wei M, Grimsgaard S |title=Herbal medicines for treatment of irritable bowel syndrome |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004116 |year=2006 |pmid=16437473 |doi=10.1002/14651858.CD004116.pub2 |url=}}</ref><ref name="pmid21649455">{{cite journal |vauthors=Yoon SL, Grundmann O, Koepp L, Farrell L |title=Management of irritable bowel syndrome (IBS) in adults: conventional and complementary/alternative approaches |journal=Altern Med Rev |volume=16 |issue=2 |pages=134–51 |year=2011 |pmid=21649455 |doi= |url=}}</ref><ref name="pmid16441466">{{cite journal |vauthors=Hussain Z, Quigley EM |title=Systematic review: Complementary and alternative medicine in the irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=23 |issue=4 |pages=465–71 |year=2006 |pmid=16441466 |doi=10.1111/j.1365-2036.2006.02776.x |url=}}</ref><ref name="pmid12578506">{{cite journal |vauthors=Spanier JA, Howden CW, Jones MP |title=A systematic review of alternative therapies in the irritable bowel syndrome |journal=Arch. Intern. Med. |volume=163 |issue=3 |pages=265–74 |year=2003 |pmid=12578506 |doi= |url=}}</ref>
Other therapies have been evaluated in patients with IBS (eg, herbs, acupuncture, enzyme supplementation, and mast cell stabilizers) but their role in the treatment of IBS remains uncertain.
* herbal medicines
 
* Apuncture<ref name="pmid19455132">{{cite journal |vauthors=Lembo AJ, Conboy L, Kelley JM, Schnyer RS, McManus CA, Quilty MT, Kerr CE, Drossman D, Jacobson EE, Davis RB |title=A treatment trial of acupuncture in IBS patients |journal=Am. J. Gastroenterol. |volume=104 |issue=6 |pages=1489–97 |year=2009 |pmid=19455132 |pmc=2694961 |doi=10.1038/ajg.2009.156 |url=}}</ref><ref name="pmid18694764">{{cite journal |vauthors=Tian SL, Wang XY, Ding GH |title=Repeated electro-acupuncture attenuates chronic visceral hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat irritable bowel syndrome model |journal=Life Sci. |volume=83 |issue=9-10 |pages=356–63 |year=2008 |pmid=18694764 |doi=10.1016/j.lfs.2008.06.027 |url=}}</ref>:  specific targets for acupuncture on serotonergic, cholinergic, and glutamatergic pathways as well as reductions in blood cortisol level <ref name="pmid18054727">{{cite journal |vauthors=Schneider A, Weiland C, Enck P, Joos S, Streitberger K, Maser-Gluth C, Zipfel S, Bagheri S, Herzog W, Friederich HC |title=Neuroendocrinological effects of acupuncture treatment in patients with irritable bowel syndrome |journal=Complement Ther Med |volume=15 |issue=4 |pages=255–63 |year=2007 |pmid=18054727 |doi=10.1016/j.ctim.2006.12.002 |url=}}</ref><ref name="pmid19891022">{{cite journal |vauthors=Ma XP, Tan LY, Yang Y, Wu HG, Jiang B, Liu HR, Yang L |title=Effect of electro-acupuncture on substance P, its receptor and corticotropin-releasing hormone in rats with irritable bowel syndrome |journal=World J. Gastroenterol. |volume=15 |issue=41 |pages=5211–7 |year=2009 |pmid=19891022 |pmc=2773902 |doi= |url=}}</ref>
 
* mind-body therapies: <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>
** hypnotherapy
** cognitive-behavioral therapy
 
* Relaxation techniques <ref name="pmid17767479">{{cite journal |vauthors=van der Veek PP, van Rood YR, Masclee AA |title=Clinical trial: short- and long-term benefit of relaxation training for irritable bowel syndrome |journal=Aliment. Pharmacol. Ther. |volume=26 |issue=6 |pages=943–52 |year=2007 |pmid=17767479 |doi=10.1111/j.1365-2036.2007.03437.x |url=}}</ref><ref name="pmid21691341">{{cite journal |vauthors=Gaylord SA, Palsson OS, Garland EL, Faurot KR, Coble RS, Mann JD, Frey W, Leniek K, Whitehead WE |title=Mindfulness training reduces the severity of irritable bowel syndrome in women: results of a randomized controlled trial |journal=Am. J. Gastroenterol. |volume=106 |issue=9 |pages=1678–88 |year=2011 |pmid=21691341 |doi=10.1038/ajg.2011.184 |url=}}</ref>
Ketotifen, a mast cell stabilizer, has been studied for the treatment of IBS based upon the theory that mast cell activation contributes to visceral hypersensitivity.<ref name="pmid20650926">{{cite journal |vauthors=Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE |title=The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome |journal=Gut |volume=59 |issue=9 |pages=1213–21 |year=2010 |pmid=20650926 |doi=10.1136/gut.2010.213108 |url=}}</ref><ref name="pmid19114087">{{cite journal |vauthors=Zhou EH, Liu HR, Wu HG, Shi Y, Wang XM, Tan LY, Yao LQ, Zhong YS, Jiang Y, Zhang LL |title=Suspended moxibustion relieves chronic visceral hyperalgesia via serotonin pathway in the colon |journal=Neurosci. Lett. |volume=451 |issue=2 |pages=144–7 |year=2009 |pmid=19114087 |doi=10.1016/j.neulet.2008.12.026 |url=}}</ref>
 
Tight-junction modulators (e.g., larazotide) for patients with evidence of immune activation or increased mucosal permeability.
 
===Disease Name===
 
* '''1 Stage 1 - Name of stage'''
** 1.1 '''Specific Organ system involved 1'''
*** 1.1.1 '''Adult'''
**** 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'''
** 2.1 '''Specific Organ system involved 1 '''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 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

Irritable bowel syndrome Microchapters

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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.
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  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.
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  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.
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  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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