US Pharm. 2012;37(12):45-48.
ABSTRACT: Irritable bowel syndrome (IBS) is a
common functional gastrointestinal disorder that typically affects
adults between the ages of 30 and 50 years, with female predominance.
Its hallmark features include abdominal discomfort, bloating, and
abnormal defecation, which may be constipation or diarrhea predominant.
IBS is difficult to diagnose and does not have an established cure at
this time. Currently, treatment strategies are patient specific,
focusing on symptom control and improvement in quality of life.
Nonpharmacologic options such as exclusion diets, dietary changes,
peppermint oil, exercise, relaxation therapy, or acupuncture have been
evaluated. Pharmacologic therapy includes antidiarrheals, laxatives,
probiotics, anticholinergics, antidepressants, antibiotics, and the
newly approved drug linaclotide. New treatment options are also
currently in the pipeline. Pharmacists can play an important role in
assisting the patient with IBS, as they are easily accessible health
Irritable bowel syndrome (IBS) is a common functional
gastrointestinal (GI) disorder that is characterized by abdominal
discomfort, bloating, and abnormal defecation.1,2 The two
main classifications of IBS are IBS with constipation predominant
(IBS-C) and IBS with diarrhea predominant (IBS-D). Patients with IBS-C
experience hard stools more than 25% of the time and loose stools less
than 25% of the time, while patients with IBS-D experience loose stools
more than 25% of the time and hard stools less than 25% of the time.3 Some patients may also have IBS with alternating diarrhea and constipation (IBS-A).4
This change in frequency and form of stool found with IBS-C, IBS-D, or
IBS-A can be noted in the symptom-based (Rome III) criteria for IBS
diagnosis (TABLE 1).
The prevalence of IBS in the United States is estimated to
be between 3% and 20%, depending on the criteria used, and it decreases
slightly with advanced age.4 Patients with new onset of IBS symptoms are typically between the ages of 30 and 50 years and are twice as likely to be women.1,3
In the U.S., IBS accounts for a significant financial
burden estimated at $1.6 billion in direct and $19.2 billion in indirect
costs.1 It also accounts for at least 1 in 10 primary care
visits and a number of specialty referrals. Unfortunately, only a
limited number of patients actually seek medical care; hence, the
disease often goes unrecognized.4 Lack of insurance or access to care may be a contributing factor.
Although the pathophysiology of IBS is not fully
understood, there are many theories regarding the etiology of the
condition. Some possible causes include genetic mutations, abnormal GI
motility, enhanced gut pain sensation (visceral hypersensitivity),
bacterial flora and inflammatory cell alteration, or psychological
changes.1,3,5 Most likely a combination of these factors leads to IBS.5
One theory concerning the pathophysiology of IBS involves
the neurotransmission between the central nervous system (CNS) and the
intestines. Numerous structures in the CNS connect to the GI tract
through serotonergic nerves that help regulate GI motility, sensation,
and secretion. In patients with IBS, an imbalance in the function of
serotonin leads to the deregulation of intestinal motility. Based on
this serotonin imbalance theory, various treatment approaches have been
IBS is difficult to diagnose. There is no reliable
biological marker for this condition, and the symptoms can mimic other
GI disorders. In an attempt to guide clinicians in establishing a
diagnosis, symptom-based criteria have been developed for IBS. The most
recent, the Rome III criteria (TABLE 1), is typically used in clinical research to diagnose and classify patients.7
Historically, IBS has been a diagnosis of exclusion.2
However, more recently, clinicians are encouraged to diagnose IBS based
on a comprehensive history, using symptom-based criteria and
considering the presence or absence of specific alarm features. These
alarm features include unintended weight loss of more than 10 lbs,
fevers or chills, high-volume diarrhea, nocturnal diarrhea, family
history of GI malignancy, and older age (≥50 years). If these features
are present, further testing is warranted, but if absent, further
testing is typically not recommended.7
SIGNS AND SYMPTOMS
IBS has a wide spectrum of symptoms with significant
interpatient variability. It is generally characterized by cramps or
lower abdominal pain. Patients may present with altered bowel habits in
volume, frequency, and consistency, as well as abdominal bloating and
flatulence. Other symptoms may include gastroesophageal reflux,
dysphagia, dyspepsia, nausea, impaired sexual function, dysmenorrhea,
and an increase in frequency and urgency to urinate.6
Since the causes of IBS have yet to be elucidated, there
are no set treatments. Currently, management depends primarily on
patient-specific symptoms and clinical response.1 A summary of pharmacologic treatments is located in TABLE 2.8 There is no cure for IBS at this time.
Nonpharmacologic Treatment Options
Dietary modification is a nonpharmacologic option for
patients with IBS. Various foods such as beans, alcohol, caffeine, and
fatty meals, and gas-producing foods such as broccoli, legumes, cabbage,
and avocado may aggravate symptoms in some patients.1,9 This
has led many patients to exclude these suspected aggravating foods from
their diet (exclusion diets), although the effectiveness of such
practices remains controversial.9 Increased intake of dietary
fiber has also been proposed as a treatment, with best evidence
supporting ispaghula/psyllium (e.g., Metamucil) over other formulations.9
Patients with IBS should monitor their symptoms using a
daily diary for 2 to 3 weeks to help identify times and severity of
symptoms, presence of aggravating factors, and possible exclusion diets.1
Homeopathic treatments have been used in the treatment of
IBS, although their effectiveness has not been fully established. One
homeopathic treatment option is acupuncture, an ancient traditional
Chinese medical practice. It is becoming more widely accepted in Western
society and may be of benefit. Peppermint oil may be another treatment
option, as it has shown to relieve symptoms and be well tolerated in
patients with IBS. Exercise, such as bicycle pedaling, and relaxation
techniques, such as muscle relaxation and conscious breathing, may help
patients by reducing stress and relieving IBS symptoms.5,10
Pharmacologic Treatment Options
IBS-Constipation Predominant: Patients with IBS-C may benefit from the use of laxatives, such as magnesium hydroxide, sorbitol, or polyethylene glycol (PEG).1 However, the only laxative that has been studied in patients with IBS is PEG.11
Lubiprostone, a chloride channel activator for the
management of IBS-C in women aged 18 years and older, increases the
movement of water and sodium into the lumen from the body, thereby
providing the desired clinical benefit. In clinical studies,
lubiprostone increased the number of weekly spontaneous bowel movements
consistency, straining, and bloating as well. Lubiprostone is
contraindicated in patients with mechanical bowel obstruction and should
be avoided in patients with preexisting diarrhea. Since lubiprostone
carries a Category C pregnancy rating, a negative pregnancy test and use
of contraception is recommended for women taking it.11
Tegaserod is indicated for the short-term treatment of women with IBS-C who are <55 years of age. This 5-HT4
receptor agonist, previously withdrawn from the market due to safety
concerns including increased risk of heart attack and stroke, is
currently available only through the FDA upon request in emergency
situations.11,12 The FDA may deny the request if there is no
reasonable basis for concluding that tegaserod may be effective for the
intended use, or if exposure to the medication would pose a significant
risk to the patient.12
The most widely used antidepressants in IBS are tricyclic
antidepressants (TCAs) and selective serotonin reuptake inhibitors
(SSRIs), as they reduce pain and improve global IBS symptoms. Their
analgesic and anxiolytic effect is thought to improve GI motility and
function. TCAs should be used with caution in elderly patients due to
the increased side effects such as urinary retention, sedation, and
Probiotics may be considered to help prevent overgrowth of
pathogenic bacteria in the GI tract as well as to reduce the
inflammatory state of the GI tract. Although efficacy studies for
probiotics are lacking due to study design, a systematic review of the
studies showed that Bifidobacterium species may be effective in improving abdominal pain, bloating, and flatulence.8
In August 2012, the FDA approved linaclotide as a
once-daily treatment for IBS-C. Linaclotide is the first-in-class
guanylate cyclase (GC-C) agonist and acts locally in the intestine with
minimal systemic exposure. It has been shown to reduce abdominal pain
and increase bowel movement frequency; however, it is contraindicated in
pediatric patients up to 6 years old and should be avoided in patients
aged 6 through 17 years because in nonclinical studies, administration
of a single, clinically relevant adult dose caused deaths in young
IBS-Diarrhea Predominant: IBS-D is
associated with increased GI motility; hence, antidiarrheals are
commonly used in symptom control. Loperamide, a widely available OTC
product, has shown to reduce GI transit time and improve diarrhea and
urgency. However, it does not improve abdominal pain and global IBS
A classic complaint in IBS-D is abdominal pain or
discomfort that is attributed to intestinal smooth-muscle spasm and an
exaggerated motility response of the small bowel and colon. As a result,
antispasmodics such as hyoscyamine, dicyclomine, belladonna, and
propantheline have been utilized to help relieve this symptom. Although
these products have traditionally been used, there is limited clinical
evidence supporting their use, especially concerning long-term
effectiveness. They are considered to provide short-term relief of
abdominal pain or discomfort. Some common side effects that limit use,
especially in the elderly, are dry mouth, dizziness, blurry vision, and
Alosetron, a 5-HT3 receptor antagonist approved by the FDA for the treatment of IBS-D, is indicated for women with severe IBS-D.11
If patients have experienced symptoms for over 6 months, have
anatomical or biochemical abnormalities of the GI tract excluded, and
have not responded adequately to conventional therapy, alosetron may be
effective.15 It has shown to significantly decrease abdominal
pain, urgency, and stool frequency while increasing stool consistency.
Due to infrequent but serious adverse events including ischemic colitis,
the product was withdrawn from the market from November 2000 to June
2002 but is now marketed with a risk management plan.11
The role of antibiotics in IBS is based on the assumption
that altered GI flora is partly responsible for the symptoms. Rifaximin,
a nonsystemic antibiotic, is indicated for traveler’s diarrhea and
hepatic encephalopathy. It has been tried in IBS patients with diarrhea
or bloating and has demonstrated improvement in symptoms.8 Antibiotics should be used with extreme caution, as bacterial resistance and side effects are a major concern.
Future Treatment Options
Due to the unmet need for treatment options, there are
various products in the pipeline for the treatment of IBS. For example,
asimadoline, an orally administered kappa opioid–receptor agonist is
being studied in IBS-D patients. Currently in phase III trials, it has
shown to produce significant improvements in pain, urgency, frequency,
and bloating.16 Pumosetrag (DDP-733), an orally available gastroprokinetic agent and locally acting 5-HT3 partial
agonist, is being developed for the potential treatment of IBS-C. It is
currently in phase II trials and has shown positive effects.17 Other emerging treatments for IBS include cholecystokinin antagonists such as loxiglumide and dexloxiglumide.18
ROLE OF PHARMACIST
Pharmacists can play an essential role for patients with
IBS by helping them identify symptoms, discussing possible treatment
options, and educating them about the disease. The community pharmacist
is in an ideal position to recognize patients who likely have IBS and
either attempt to self-medicate with various OTC products such as herbal
supplements or have prescriptions for antidiarrheals or laxatives.
Proactive questioning of the patient will allow the pharmacist to assess
the appropriateness of the medications or identify a need for referral
to other health care professionals for further evaluation. Finally, it
is also important for the pharmacist to reassure the patient that IBS
remains a manageable illness for the most part.
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Greenwood Village, CO: Thomson Reuters (Healthcare) Inc; updated
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