Irritable Bowel Syndrome Management

Irritable bowel syndrome patients do not have an increased risk of organic diseases compared to individuals without irritable bowel syndrome; therefore, the routine use of extensive diagnostic tests in irritable bowel syndrome suspected patients is not necessary. An accurate history collection is needed for establishing the probability of a patient having an underlying organic cause of symptoms. Patients who present with any of the alarm signs and symptoms listed below may have a higher incidence of organic disease, and therefore routine diagnostic tests in these patients are considered appropriate.

Alarm Signs and Symptoms

The alarm signs and symptoms that should be monitored include:

• Age ≥50 years
• Ascites
• Family history of colon cancer, ovarian cancer, inflammatory bowel disease, celiac sprue, or recurring fever
• Inflammatory markers for inflammatory bowel disease
• More loose or more frequent stools or both, persisting for >6 weeks in an individual >60 years old
• Nocturnal symptoms (eg pain, defecation)
• Palpable lymphadenopathy, abdominal or rectal mass
• Recent change in bowel habit
• Recent medication use (antibiotics)
• Rectal bleeding, hematochezia, melena, or occult blood in the stool
• Unexplained iron-deficiency anemia
• Unintended weight loss

Determine Severity of Symptoms

Irritable bowel syndrome symptoms can significantly diminish the quality of life of the patient. There is no data available to guide recommendations about the threshold to treat irritable bowel syndrome. For some patients, it may be enough to be assured that their symptoms do not represent a life-threatening illness or cancer. Treatment should be offered to patients if it is felt that the symptoms are diminishing their quality of life. Below are general classification suggestions:

Mild

The symptoms are mild if there are infrequent symptoms with little or no functional impairment or psychologic disturbance. Treatment should be focused on the establishment of a physician-patient relationship, patient education, reassurance, dietary and medication modification, and fiber supplementation.

Moderate

The symptoms are moderate if there are disruptions of the patient’s normal daily activities due to the exacerbations of symptoms, and they may demonstrate psychologic distress. Symptom monitoring is recommended to identify precipitating factors. Diet modifications, behavioral changes, and psychotherapy may improve the clinical picture. Pharmacologic intervention should be used to control symptom flares.

Severe

The symptoms are severe if there is unrelenting pain often associated with underlying psychosocial difficulties. Treatment may involve behavioral modification, psychoactive drugs, and referral to a pain center.

Specialist Referral 

Specialist referral is recommended in patients who present with alarm signs and symptoms. This is indicated if specialized diagnostic procedures or other appropriate tests are warranted (eg colonoscopy, sigmoidoscopy, barium enema, fecal occult blood tests, stool for ova and parasites, or stool for culture). Though the diagnostic yield of colonoscopy is low among patients with irritable bowel syndrome, it may be of value in ruling out organic diseases (eg IBD and malignancy) and microscopic colitis in patients presenting with alarm signs (eg recent change in bowel habits, unexplained weight loss, blood in the stool, and anemia). Diagnostic colonoscopy may also be performed in patients <45 years old with irritable bowel syndrome without alarm signs who are unresponsive to treatment. A routine colon cancer screening is recommended for all patients ≥50 years old and >40 years old in areas with a high prevalence of gastric cancer.

Establishing Therapeutic Relationship

The cornerstone of irritable bowel syndrome therapy is a strong physician-patient relationship, education, and reassurance, which may reduce the need for further consultation and may be therapeutic. One should establish a therapeutic relationship by listening to the patient, by addressing concerns, by identifying and discussing the patient’s beliefs, by explaining the disease state such as the nature, causes, aggravating factors, and prognosis, by reassuring the patient of the benign nature of irritable bowel syndrome, and by educating the patient on trigger avoidance and stress management.

General Therapeutic Principles for Pharmacotherapy in Irritable Bowel Syndrome

The goal of therapy is to improve global irritable bowel syndrome symptoms, which include abdominal discomfort or bloating and altered bowel habits. Not only should therapy be directed at altered bowel habits (eg constipation, diarrhea, or fecal urgency) but should also address abdominal discomfort. Therapy should be given to those in whom there is an impact on the quality of life from irritable bowel syndrome symptoms. Treat comorbid psychiatric disease accordingly.

Symptom-Based Descriptions

Irritable bowel syndrome symptoms may fluctuate over time and vary between individuals. IBS-C often changes to constipation alone or irritable bowel syndrome alternating between constipation and diarrhea or any other functional GI disorders over time. Therefore, symptom-based descriptions may be used to guide management (eg IBS-D or IBS-C). 

PHARMACOLOGICAL THERAPY FOR IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C)

Bulk-Producing Laxatives

Example drugs: Ispaghula (Psyllium), Methylcellulose, Polycarbophil

Patients with constipation should first attempt to increase fiber in their diet; if this does not improve symptoms, then the addition of Ispaghula may be tried. A few small studies conducted in older adults showed similar effectiveness of Polycarbophil and Methylcellulose to Ispaghula. Ispaghula husk is moderately effective for constipation and is associated with an overall improvement in patients with irritable bowel syndrome. Patients should be warned that bloating and abdominal distension may occur, especially at the start of fiber therapy, but may decrease over time or with a dose reduction. Wheat or corn bran has not been found to improve global irritable bowel syndrome symptoms compared to placebo.

Osmotic Laxatives

Example drugs: Lactulose, Milk of Magnesia, Sorbitol, Magnesium citrate, Polyethylene glycol (PEG)/Macrogol

If dietary fiber and bulk-producing laxatives are not effective, osmotic laxatives may be tried, though there are no published studies with these laxatives in IBS-C patients, and they should not be given to patients with renal dysfunction. Polyethylene glycol improves the frequency and consistency of bowel movement but not pain and other symptoms of irritable bowel syndrome. This is widely available and has lesser side effects compared with Lactulose or Milk of Magnesia.

Guanylate Cyclase-C Receptor Agonists

 Linaclotide

Linaclotide is a non-absorbed 14-amino acid peptide that stimulates the guanylate cyclase-C receptor on enterocytes, resulting in intestinal chloride and bicarbonate secretion leading to increased intestinal fluid and transit. This is recommended for patients with moderate-severe IBS-C and also for overall symptom improvement. Randomized controlled trials showed improvement in global symptoms of irritable bowel syndrome.

Plecanatide

Plecanatide is a non-absorbed 16-amino acid peptide that stimulates the guanylate cyclase-C receptor on enterocytes, leading to fluid and electrolyte secretion and reduced visceral hypersensitivity. This is recommended for overall symptom improvement in patients with IBS-C and has comparable efficacy and safety as Linaclotide.

Serotonin 5-HT₄ Receptor Agonists

Prucalopride

Prucalopride is a prokinetic that has been shown in clinical trials to be effective for chronic constipation. This is an alternative for patients unresponsive to conventional laxatives. Further studies in patients with IBS-C are needed to confirm efficacy and safety.

Tegaserod 

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Tegaserod is a partial agonist of the 5-HT₄ receptor, which stimulates gastrointestinal motility and increases fluid in the GI tract. This has been shown to be more effective than placebo at relieving global irritable bowel syndrome symptoms in women with IBS-C and IBS-M. This is an alternative agent for women <65 years old with ≤1 risk factor for cardiovascular (CV) disease and without a history of ischemic CV disease (eg myocardial infarction [MI], transient ischemic attack [TIA], angina) who have inadequately responded to secretagogues.

Type 2 Chloride Channel Agonist

Lubiprostone

Lubiprostone activates type 2 chloride channels, thereby increasing chloride influx into the GI tract lumen and resulting in acceleration of intestinal transit. This may be considered in women with IBS-C with persistent constipation despite therapy with osmotic laxatives. This improves stool consistency and abdominal pain in women at 1 month of use and is better than placebo in improving abdominal bloating at 3 months. The initial response may be delayed, but improvement in global symptoms is maintained or increases over time.

Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitor

Tenapanor

Tenapanor is a locally acting and minimally absorbed small-molecule inhibitor of the GI sodium/hydrogen exchanger isoform 3, which is responsible for sodium absorption, resulting in decreased absorption of sodium and phosphate, increased water secretion into the intestinal lumen, shortened intestinal transit time, and softened stool consistency. This may be considered in patients with IBS-C who fail other therapies for constipation. Clinical trials showed improvement in spontaneous bowel movements and abdominal pain when compared with placebo in patients with IBS-C.

PHARMACOLOGICAL THERAPY FOR IRRITABLE BOWEL SYNDROME WITH DIARRHEA (IBS-D)

Antidiarrheals

Bile Acid Sequestrants

Example drugs: Cholestyramine, Colesevelam, Colestipol



Bile acid sequestrants may be considered in a subgroup of irritable bowel syndrome patients with diarrhea secondary to cholecystectomy or bile acid malabsorption.

Intestinal Adsorbents   

Example drugs: Dioctahedral smectite (Diosmectite)  

Intestinal adsorbents protect the GI mucosa by interacting with the glycoprotein of mucus, thus increasing the resistance of the mucosal gel in response to aggressive agents. 

Synthetic Opiates

Example drugs: Diphenoxylate/Atropine, Eluxadoline, Loperamide

Synthetic opiates may be used in patients suffering from diarrhea, as they can reduce loose stools, urgency, and fecal soiling.

Loperamide 

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Loperamide inhibits peristalsis and antisecretory activity and prolongs intestinal transit time with limited penetrance of the blood-brain barrier. This significantly improves diarrheal symptoms in patients with irritable bowel syndrome but is not recommended for continuous use due to lack of significant overall symptom improvement in irritable bowel syndrome patients.

Eluxadoline

Eluxadoline is a mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist in the enteric nervous system. This decreases muscle contractility, inhibits water and electrolyte secretion, and increases rectal sphincter tone. This may be considered for overall symptom improvement in patients with IBS-D. This is contraindicated in patients with a history of alcohol abuse or addiction, biliary duct obstruction, pancreatitis, severe liver problems, and patients who underwent cholecystectomy due to increased risk of pancreatitis.



Serotonin 5-HT₃ Receptor Antagonists

Alosetron

Alosetron has been shown to be more effective than placebo at relieving global irritable bowel syndrome symptoms in female IBS patients with diarrhea. The United States Food and Drug Administration (US FDA) approval is only for use in women with severe diarrhea-predominant irritable bowel syndrome for 6 months and who have failed to respond to conventional IBD therapy. Severe IBS-D is defined as ≥1 of the following symptoms: Frequent and severe abdominal pain or discomfort, frequent bowel urgency or fecal incontinence, and/or disability or restriction of daily activities due to irritable bowel syndrome. This decreases gut transit in non-IBS and irritable bowel syndrome patients, enhances basal sodium and fluid absorption, and relaxes the left colon, thereby reducing the perception of fluid distension in patients with IBD. Cases of ischemic colitis and serious constipation complications have occurred with the use of Alosetron; therefore, the patient and physician need to carefully consider the risk or benefit profile before deciding to use it.

Ondansetron

Ondansetron has been found to be helpful in improving stool consistency, urgency, and frequency and bloating in IBS-D.

Ramosetron

Ramosetron is a promising therapeutic agent for male patients with IBS-D. This inhibits 5-HT₃ receptor antagonism in the vagal afferent neurons and myenteric plexus. A study demonstrated higher rates of relief of overall irritable bowel syndrome symptoms in male patients with IBS-D than placebo. Trials show that the incidence of constipation is lower among patients treated with Ramosetron, and no ischemic colitis was reported.

Antibiotic

Rifaximin is a safe and effective agent for the treatment of abdominal pain and diarrhea in patients with IBS-D. This eradicates bacterial overgrowth, and retreatment with Rifaximin may be considered in patients with IBS-D with an initial response to Rifaximin who develop recurrent symptoms. Consider evaluating for severe infectious diarrhea (eg C difficile enterocolitis) if diarrhea does not improve or worsens following treatment with Rifaximin.

PHARMACOLOGICAL THERAPY FOR ABDOMINAL PAIN AND BLOATING

Antispasmodics 







Antispasmodics may be used in patients with all irritable bowel syndrome subtypes for the treatment of abdominal pain and spasms. This may be considered for pain or bloating, especially when exacerbated by meals. The smooth muscle relaxants, Alverine citrate, Cimetropium, Hyoscine, Hyoscyamine, Dicyclomine, Mebeverine, Octylonium bromide (Otilonium bromide), Pinaverium bromide, Trimebutine, and Peppermint oil may be more effective than placebo in improving irritable bowel syndrome symptoms. This is best used on a short-term, as-needed basis, up to three times a day for acute attacks of pain or before meals if there are postprandial symptoms.

Tricyclic Antidepressants (TCAs)

Though not an approved indication, low-dose TCAs may be considered for severe irritable bowel syndrome in which pain is more constant or disabling. Tricyclic antidepressants have been shown to significantly improve abdominal pain and symptoms in irritable bowel syndrome patients compared with placebo. These relieve abdominal pain associated with irritable bowel syndrome independent of their effect on mood and may be more effective in IBS-D. The effect may be due to a reduction in the sensitivity of peripheral nerves or to alterations in the brain.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors have been shown to be more effective than placebo at relieving global irritable bowel syndrome symptoms. These may be beneficial for patients exhibiting symptoms of anxiety and also proven to reduce abdominal pain greatly in IBS-C. These are recommended only when there is treatment failure after TCA therapy. Advise patients to strictly follow up after 4 weeks and every 6-12 months while on SSRI therapy.

Antibiotics

Some clinical trials have shown that a non-absorbable antibiotic, Rifaximin, is more effective for global improvement of irritable bowel syndrome and bloating as compared to placebo. No studies are available to support long-term use of antibiotics for the management of irritable bowel syndrome. There is not enough available evidence to support the use of Neomycin, Metronidazole, and Clarithromycin for improvement of symptoms of irritable bowel syndrome. 

Lifestyle and Dietary Modification

Exercise

Increasing exercise can result in overall symptom improvement in patients with irritable bowel syndrome. A randomized trial showed that increased physical activity at 20-60 minutes of moderate to vigorous level improved the severity of irritable bowel syndrome symptoms with less likelihood of worsening than compared with the control group.

Dietary Modifications 

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Dietary monitoring may be helpful to have patients keep a diary of food intake, symptoms including severity, and possible exacerbating factors (eg emotional issues) for 2-3 weeks. The physician may then be able to make lifestyle or diet modification suggestions based on these. Elimination or an empirical diet is recommended for 2-4 weeks when specific foods are suspected of causing irritable bowel syndrome symptoms; if no improvement after 4 weeks, consider other factors or refer to a specialist.

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is recommended to reduce irritable bowel syndrome symptoms. Low FODMAP diet (LFD) consists of three phases: Restriction phase wherein dietary FODMAP intake is reduced substantially to determine whether symptoms in patients with irritable bowel syndrome can be linked to FODMAP intake, which should not last >4-6 weeks followed by a reintroduction phase of FODMAP foods for 6-10 weeks, then personalization based on results from reintroduction.

Supplementation with soluble and poorly fermentable fiber is recommended for overall symptom improvement. Psyllium, but not wheat bran, is recommended for overall symptom improvement. If lactose intolerance is suspected, a trial period of a low-lactose diet may be advised; if confirmed via a positive lactose hydrogen breath test, a low-lactose diet is highly recommended. A gluten-free diet may be advised to patients with IBS-D without celiac disease.

Probiotics (eg Lactobacillus spp, Bifidobacterium spp and Saccharomyces spp) may be considered to improve symptoms such as pain and bloating or flatulence. The use of metabolomic markers or unidentified gut biomarkers may help improve the efficacy of probiotics, but further studies are needed. Additional evidence supporting the efficacy of probiotics is necessary before they can be recommended for the treatment of irritable bowel syndrome.

Other general dietary modifications include drinking at least 2,000 mL of fluid daily, reducing intake of alcohol, caffeinated drinks, or soft drinks; avoiding dairy products, fatty foods, and foods that produce gas (eg beans, raisins, prunes, onions, etc), restricting fresh fruit intake to three portions daily; and avoiding Sorbitol if the patient has diarrhea.

Irritable Bowel Syndrome with Constipation (IBS-C)

A 3-month trial with ground linseeds is recommended for IBS-C patients with abdominal pain and bloating. Suggest to the patient to increase dietary intake of fiber to 20-35 g/day. Dietary fiber assists with constipation but does not improve abdominal pain.

Behavioral Therapy 

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Identify the signs of a psychological disorder, as psychological disorders and irritable bowel syndrome are often comorbid conditions. Consider administering psychological treatments in cases wherein a significant association between stress and symptoms exists or in patients who are unresponsive after 3-6 months of treatment with first- or second-line agents. Psychological treatments that have been used include relaxation therapy, biofeedback, hypnotherapy, cognitive therapy, and psychotherapy. Various clinical trials have shown that cognitive behavioral therapy, dynamic psychotherapy and hypnotherapy are beneficial for irritable bowel syndrome patients except relaxation therapy. Cognitive behavioral therapy can be very effective for patients with persistent irritable bowel syndrome symptoms and may also benefit those with poor stress management.