As with other functional disorders, the most important interventions the clinician can offer are reassurance, education, and support. This includes identifying and responding to the patient’s concerns, careful explanation of the pathophysiology and natural history of the disorder, setting realistic treatment goals, and involving the patient in the treatment process. Because irritable bowel symptoms are chronic, the patient’s reasons for seeking consultation at this time should be determined. These may include major life events or recent psychosocial stressors, dietary or medication changes, concerns about serious underlying disease, or reduced quality of life and impairment of daily activities. In discussing with the patient the importance of the mind-gut interaction, it may be helpful to explain that alterations in visceral motility and sensitivity may be exacerbated by environmental, social, or psychological factors such as foods, medications, hormones, and stress. Symptoms such as pain, bloating, and altered bowel habits may lead to anxiety and distress, which in turn may further exacerbate bowel disturbances due to disordered communication between the gut and the central nervous system. Fears that the symptoms will progress, require surgery, or degenerate into serious illness should be allayed. The patient should understand that irritable bowel syndrome is a chronic disorder characterized by periods of exacerbation and quiescence. The emphasis should be shifted from finding the cause of the symptoms to finding a way to cope with them. Moderate exercise is beneficial. Clinicians must resist the temptation to chase chronic complaints with new or repeated diagnostic studies.
Patients commonly report dietary intolerances. Proposed mechanisms for dietary intolerance include food allergy, hypersensitivity, effects of gut hormones, changes in bacterial flora, increased bacterial gas production (arising in the small or large intestine), and direct chemical irritation. Fatty foods, alcohol, caffeine, spicy foods, and grains are poorly tolerated by many patients with irritable bowel syndrome. In patients with diarrhea, bloating, and flatulence, lactose intolerance should be excluded with a hydrogen breath test or a trial of a lactose-free diet. A host of poorly absorbed, fermentable, monosaccharides and short-chain carbohydrates (FODMAPs) may exacerbate bloating, flatulence, and diarrhea in some patients. These include six food groups: fructose (corn syrups, apples, pears, honey, watermelon, raisins), lactose, fructans (garlic, onions, leeks, asparagus, artichokes), wheat-based products (breads, pasta, cereals, cakes), sorbitol (stone fruits), and raffinose (legumes, lentils, brussel sprouts, soybeans, cabbage). Dietary restriction of these fermentable carbohydrates for 2–4 weeks may improve symptoms (especially abdominal pain and bloating) in 50–65% of patients. Responders should gradually reintroduce different FODMAPs to identify food triggers. In a 2018 randomized placebo-controlled crossover trial, ingestion of alpha-galactosidase supplement (“Beano”) with meals containing foods with high galactoside content (eg, beans, peas, lentils, soy) significantly improved bowel symptoms. Gluten has not been demonstrated to increase bowel symptoms independent of other FODMAPs, and a gluten-free diet is not recommended.
Poorly fermentable soluble fiber (psyllium, oatmeal) improves global symptoms in many patients and is recommended by the 2018 American College of Gastroenterology guideline. Fermentable or insoluble fiber (bran) may increase gas and bloating. The guideline does not recommend a gluten-free diet.
C. Pharmacologic Measures
More than two-thirds of patients with irritable bowel syndrome have mild symptoms that respond readily to education, reassurance, and dietary interventions. Drug therapy should be reserved for patients with moderate to severe symptoms that do not respond to conservative measures. These agents should be viewed as being adjunctive rather than curative. Given the wide spectrum of symptoms, no single agent is expected to provide relief in all or even most patients. Nevertheless, therapy targeted at the specific dominant symptom (pain, constipation, or diarrhea) may be beneficial.
Anticholinergic agents are used by some practitioners for treatment of acute episodes of pain or bloating despite a lack of well-designed trials demonstrating efficacy. Available agents include hyoscyamine, 0.125 mg orally (or sublingually as needed) or sustained-release, 0.037 mg or 0.75 mg orally twice daily; dicyclomine, 10–20 mg orally; or methscopolamine 2.5–5 mg orally before meals and at bedtime. Anticholinergic side effects are common, including urinary retention, constipation, tachycardia, and dry mouth. Hence, these agents should be used with caution in older patients and in patients with constipation. Peppermint oil formulations (which relax smooth muscle) may be helpful.
Loperamide (2 mg orally three or four times daily) is effective for the treatment of patients with diarrhea, reducing stool frequency, liquidity, and urgency. It may best be used “prophylactically” in situations in which diarrhea is anticipated (such as stressful situations) or would be inconvenient (social engagements). Increased intracolonic bile acids due to alterations in enterohepatic circulation may contribute to diarrhea in a subset of patients with diarrhea. An empiric trial of bile salt-binding agents (cholestyramine 2–4 g with meals; colesevelam, 625 mg, 1–3 tablets twice daily) may be considered. Eluxadoline (75–100 mg twice daily) is an opioid antagonist that was approved by the FDA in 2016 for treatment of irritable bowel with diarrhea. In phase III trials, eluxadoline decreased abdominal pain and improved stool consistency in approximately 25% of patients versus 16–19% with placebo; however, sphincter of Oddi dysfunction and pancreatitis developed in a small percentage (0.5%) of patients. Given its minimal efficacy, adverse side effect profile, and unproven benefit versus loperamide, further study is needed before its use can be recommended.
3. Anticonstipation agents
Treatment with oral osmotic laxatives polyethylene glycol 3350 (Miralax, 17–34 g/day) may increase stool frequency, improve stool consistency, and reduce straining. Lactulose or sorbitol produces increased flatus and distention, which are poorly tolerated in patients with irritable bowel syndrome and should be avoided. Lubiprostone (8 mcg orally twice daily), linaclotide (290 mcg orally once daily), plecanatide (3 mg orally once daily), and tegaserod (6 mg orally twice daily) are newer agents approved for treatment of irritable bowel syndrome with constipation. Through different mechanisms, they stimulate increased intestinal chloride and fluid secretion, resulting in accelerated colonic transit. In clinical trials, lubiprostone led to global symptom improvement in 18% of patients compared with 10% of patients who received placebo. Trials of linaclotide included similar patient populations but measured different, FDA-defined primary end points. Higher combined response rates (defined as greater than 30% reduction in abdominal pain and more than three spontaneous bowel movements per week, including an increase of one or more from baseline) were found in 12.5% of linaclotide-treated patients compared with 4% of placebo-treated patients. Plecanatide was FDA approved in 2018 for the treatment of irritable bowel syndrome with constipation. Across two phase III trials, the proportion of patients with clinical response after 12 weeks of therapy (FDA-defined primary end points) with plecanatide (3 mg orally once daily) was 26% versus 16% with placebo. Tegaserod, a 5-HT4-receptor agonist, was originally approved by the FDA in 2002 for irritable bowel syndrome with constipation, but voluntarily withdrawn from the market in 2007 because of cardiovascular safety concerns. But in March 2019, it was reapproved by the FDA for women under age 65 after evaluation of clinical data from 29 placebo-controlled trials and newer treatment outcome data. Patients with intractable constipation should undergo further assessment for slow colonic transit and pelvic floor dysfunction (see Constipation, above).
Patients with predominant symptoms of pain or bloating may benefit from low doses of tricyclic antidepressants, which are believed to have effects on motility, visceral sensitivity, and central pain perception that are independent of their psychotropic effects. Because of their anticholinergic effects, these agents may be more useful in patients with diarrhea-predominant than constipation-predominant symptoms. Oral nortriptyline, desipramine, or imipramine may be started at a low dosage of 10 mg at bedtime and increased gradually to 50–150 mg as tolerated. Response rates do not correlate with dosage, and many patients respond to doses of 50 mg or less daily. Side effects are common, and lack of efficacy with one agent does not preclude benefit from another. Agents with higher anticholinergic activity may improve diarrhea but worsen constipation. Improvement should be evident within 4 weeks. The oral serotonin reuptake inhibitors (sertraline, 25–100 mg daily; citalopram, 10–20 mg; paroxetine, 20–50 mg daily; or fluoxetine, 10–40 mg daily) may be used to treat irritable bowel symptoms as well as treat mood disorders. SSRIs may accelerate gastrointestinal transit and improve constipation. Anxiolytics should not be used chronically in irritable bowel syndrome because of their habituation potential. Patients with major depression or anxiety disorders should be identified and treated with therapeutic doses of appropriate agents.
5. Serotonin receptor antagonists
Serotonin is an important mediator of gastrointestinal motility and sensation. In patients with irritable bowel syndrome with diarrhea, 5-HT3 antagonists may reduce diarrhea and improve overall symptoms through central and peripheral mechanisms. Alosetron is a 5-HT3 antagonist that is FDA-approved for the treatment of women with severe irritable bowel syndrome with predominant diarrhea. Alosetron (0.5–1 mg orally twice daily) reduces symptoms of pain, cramps, urgency, and diarrhea in 50–60% of women compared with 30–40% treated with placebo. Efficacy in men has not been demonstrated. Unfortunately, due to cases of severe constipation and a small (1:1000) but significant risk of ischemic colitis, alosetron is restricted to women with severe irritable bowel syndrome with diarrhea who have not responded to conventional therapies and who have been educated about the relative risks and benefits of the agent. It should not be used in patients with constipation. A randomized crossover trial of another 5-HT3 antagonist, ondansetron 4–8 mg three times daily, showed overall superior symptom improvement, including stool frequency, consistency, and urgency. At this time, 5-HT3 antagonists may be considered after careful discussion of the risks and benefits in carefully selected patients with severe diarrhea-predominant irritable bowel syndrome.
6. Nonabsorbable antibiotics
Rifaximin may be considered in patients with refractory symptoms, especially bloating. A 2012 meta-analysis identified a 9.9% greater improvement in bloating with rifaximin compared with placebo, a modest gain that is similar to other less expensive therapies. Symptom improvement may be attributable to suppression of bacteria in either the small intestine or colon, resulting in decreased bacterial carbohydrate fermentation, diarrhea, and bloating.
Meta-analyses of small controlled clinical trials of probiotics report improved symptoms of pain, bloating, and flatulence in some patients. It is hypothesized that alterations in gut flora may reduce symptoms through suppression of inflammation or reduction of bacterial gas production, resulting in reduced distention, flatus, and visceral sensitivity. Such therapy is attractive because it is safe, well tolerated, and inexpensive. Although promising, further study is needed to define the efficacy and optimal formulations of probiotic therapy. The 2018 American College of Gastroenterology guideline gave probiotics a weak recommendation.
D. Psychological Therapies
Cognitive-behavioral therapies, relaxation techniques, and hypnotherapy appear to be beneficial in some patients. Patients with underlying psychological abnormalities may benefit from evaluation by a psychiatrist or psychologist. Patients with severe disability should be referred to a pain treatment center.