Irritable bowel syndrome medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical therapy
Initial treatments
Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opioidor opioid analogs such as loperamide, diphenoxylate or codeine in diarrhea-predominant IBS for mild symptoms.[1][2][3]
Laxatives
For patients who do not adequately respond to dietary fiber, osmotic agents such as polyethylene glycol, sorbitol, and lactulose can help avoid 'cathartic colon' which has been associated with stimulant laxatives.[4] Among the osmotic laxatives, 17 to 26 grams/day of polyethylene glycol (PEG) has been well studied.
Antispasmodics
The use of antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine) may help patients, especially those with cramps or diarrhea. A meta-analysis by the Cochrane Collaboration concludes that if 6 patients are treated with antispasmodics, 1 patient will benefit (number needed to treat = 6).[1] Antispasmodics can be divided in two groups: neurotropics and musculotropics. Neurotropics, such as atropine, act at the nerve fibre of the parasympathicus but also affect other nerves and have side effects. Musculotropics such as mebeverine act directly at the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since this action is not mediated by the autonomic nervous system, the usual anticholinergic side effects are absent. Antispasmodic drugs are also available in combination with tranquilizers or barbiturates, such as chlordiazepoxide and Donnatal. The value of the combination therapies has not been established.
Drugs affecting serotonin (5-HT)
Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms.[5] Serotonin stimulates the gut motility and so agonists can help constipation predominate irritable bowel while antagonists can help diarrhea predominant irritable bowel:
Agonists
- Tegaserod, a selective 5-HT4 agonist for IBS-C, is available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. On March 30, 2007, the Food and Drug Administration (FDA) requested that Novartis Pharmaceuticals voluntarily discontinue marketing of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events (heart problems) associated with use of the drug. Novartis agreed to voluntarily suspend marketing of the drug in the United States and in many other countries. On July 27, 2007 the Food and Drug Administration (FDA) approved a limited treatment IND program for Zelnorm in the USA to allow restricted access to the medication for patients in need if no comparable alternative drug or therapy is available to treat the disease. The USA FDA had issued two previous warnings about the serious consequences of Tegaserod. In 2005, Tegaserod was rejected as an IBS medication by the European Union. Tegaserod, marketed as Zelnorm in the United States, was the only agent approved to treat the multiple symptoms of IBS (in women only), including constipation, abdominal pain and bloating. A meta-analysis by the Cochrane Collaboration concludes that if 17 patients are treated with typical doses of tegaserod, 1 patient will benefit (number needed to treat = 17).[6]
- Selective serotonin reuptake inhibitor anti-depressants (SSRIs), because of their serotonergic effect, would seem to help IBS, especially patients who are constipation predominant. Initial crossover studies[7] and randomized controlled trials[8][9][10] support this role.
Antagonists
- Alosetron, a selective 5-HT3 antagonist for IBS-D, which is only available for women in the United States under a restricted access program, due to severe risks of side-effects if taken mistakenly by IBS-A or IBS-C sufferers.
- Cilansetron, also a selective 5-HT3 antagonist, is undergoing further clinical studies in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew Cilansetron from the United States regulatory approval process after receiving a "not approvable" action letter from the FDA requesting additional clinical trials.
Other agents
Anti-depressants include both tricyclic antidepressants (TCAs) and the newer selective serotonin reuptake inhibitors(SSRIs). In addition to improving symptoms via treating any co-existing depression, TCAs have anti-cholinergic actions while SSRIs are serotonergic. Thus in theory, TCAs would best treat diarrhea-predominant IBS while SSRIs would best treat constipation-predominant IBS. A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve (number needed to treat = 3).[11] A separate randomized controlled trial found that TCAs are best for patients with diarrhea-predominant IBS.[12]
Recent studies have suggested that rifaximin can be used as an effective treatment for abdominal bloating andflatulence,[13][14] giving more credibility to the potential role of bacterial overgrowth in some patients with IBS.[15]
The multi-herbal extract Iberogast was found to be significantly superior to placebo via both an abdominal pain scale and an IBS symptom score after four weeks of treatment.[16]
Enteric coated peppermint oil capsules has been advocated for IBS symptoms in adults and children;[17] however, results from trials have been inconsistent.[18][19]
For severe diarrhea-predominant IBS, more potent opioids may be used, such as codeine or propoxyphene; refractory cases may even be treated with paregoric, or, more rarely, deodorized tincture of opium or morphine sulfate. The use of opioids remains controversial due to the lack of evidence supporting their benefit and the potential risk of tolerance,physical dependence and addiction.[20]
Cannabis has theoretical support for its role,[21][22] but has not been subject of clinical studies. Although illegal in many counties, it has been prescribed to patients in nations such as Canada. Some of the argued benefits of cannabis are the reduction of pain and nausea, appetite stimulation, and assisting in falling asleep.
References
- ↑ 1.0 1.1 Quartero A, Meineche-Schmidt V, Muris J, Rubin G, de Wit N. "Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome". Cochrane Database Syst Rev: CD003460. PMID 15846668.
- ↑ 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.
- ↑ 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.
- ↑ Joo J, Ehrenpreis E, Gonzalez L, Kaye M, Breno S, Wexner S, Zaitman D, Secrest K (1998). "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". J Clin Gastroenterol. 26 (4): 283–6. PMID 9649012.
- ↑ Talley N (2001). "Serotoninergic neuroenteric modulators". Lancet. 358 (9298): 2061–8. PMID 11755632.
- ↑ Evans B, Clark W, Moore D, Whorwell P. "Tegaserod for the treatment of irritable bowel syndrome". Cochrane Database Syst Rev: CD003960. PMID 14974049.
- ↑ Tack J, Broekaert D, Fischler B, Oudenhove L, Gevers A, Janssens J (2006). "A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome". Gut. 55 (8): 1095–103. PMID 16401691.
- ↑ Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R (2005). "The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study". Aliment Pharmacol Ther. 22 (5): 381–5. PMID 16128675.
- ↑ Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B (2003). "The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome". Gastroenterology. 124 (2): 303–17. PMID 12557136.
- ↑ Tabas G, Beaves M, Wang J, Friday P, Mardini H, Arnold G (2004). "Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial". Am J Gastroenterol. 99 (5): 914–20. PMID 15128360.
- ↑ Jackson J, O'Malley P, Tomkins G, Balden E, Santoro J, Kroenke K (2000). "Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis". Am J Med. 108 (1): 65–72. PMID.
- ↑ Drossman D, Toner B, Whitehead W, Diamant N, Dalton C, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris C, Blackman C, Hu Y, Jia H, Li J, Koch G, Bangdiwala S (2003). "Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders". Gastroenterology. 125 (1): 19–31. PMID.
- ↑ Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I (2006). "A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence". Am J Gastroenterol. 101 (2): 326–33. PMID.
- ↑ Pimentel M, Park S, Mirocha J, Kane S, Kong Y (2006). "The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial". Ann Intern Med. 145 (8): 557–63. PMID.
- ↑ Quigley EM (2006). "Germs, gas and the gut; the evolving role of the enteric flora in IBS". Am J Gastroenterol. 101 (2): 334–5. PMID.
- ↑ Madisch A, Holtmann G, Plein K, Holz J (2004). "Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial". Aliment Pharmacol Ther. 19: 271&ndash, 9.
- ↑ Hadley SK, Gaarder SM (2005). "Treatment of irritable bowel syndrome". Am Fam Physician. 72 (12): 2501–6. PMID.
- ↑ Nash P, Gould S, Bernardo D (1986). "Peppermint oil does not relieve the pain of irritable bowel syndrome". Br J Clin Pract. 40 (7): 292–3. PMID.
- ↑ Liu J, Chen G, Yeh H, Huang C, Poon S (1997). "Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial". J Gastroenterol. 32 (6): 765–8. PMID.
- ↑ Warfield, Carol A. (2003). Principles and Practice of Pain Medicine. McGraw-Hill Professional. ISBN 0071443495. Unknown parameter
|coauthors=ignored (help) - ↑ Massa F, Storr M, Lutz B (2005). "The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract". J Mol Med. 83 (12): 944–54. PMID.
- ↑ Russo E. "Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?". Neuro Endocrinol Lett. 25 (1–2): 31–9. PMID.