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Medications for Irritable Bowel Syndrome
Initial treatments prescribed by doctors
Medications may consist of stool softeners and
laxatives in constipation-predominant IBS, and antidiarrheals
(e.g., opioid or opioid analogs such as loperamide,
diphenoxylate or codeine in diarrhea-predominant IBS for mild
symptoms.[83][84][85]
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.[86] 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).[83] 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
Drugs affecting serotonin (5-HT) in the
intestines can help reduce symptoms.[87] 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).[88]
* 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[89] and randomized controlled
trials[90][91][92] 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).[93] A separate randomized
controlled trial found that TCAs are best for patients with
diarrhea-predominant IBS.[94]
Recent studies have suggested that rifaximin
can be used as an effective treatment for abdominal bloating and
flatulence,[95][51] giving more credibility to the potential
role of bacterial overgrowth in some patients with IBS.[96]
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