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Management/Irritable Bowel Syndrome


Case

A 28-year-old woman is referred to a gastroenterologist by her primary care physician for evaluation and management of abdominal pain and constipation for the past year. The patient reports having intermittent abdominal pain and bloating that are associated with feeling constipated. Her constipation symptoms include hard stools, difficulty evacuating stools, and sensation of incomplete evacuation. She has a bowel movement every 1 to 2 days. Her abdominal pain and bloating improve after having a bowel movement. She has had similar symptoms since college, which she associated with stress, but they were milder and she never sought care for them. Now her symptoms, especially the pain and bloating, make it difficult for her to concentrate on her work, and she misses work 1-2 days per month. Her sleep is sometimes disturbed, particularly when her symptoms are worse and she feels tired during the day. She has tried increasing her fluid intake and different over-the-counter laxatives and fiber supplements. While these medications help to loosen her stool, she does not like taking them. The discomfort and urgency caused by the laxatives are very bothersome, and she still has pain and bloating which is sometimes increased with the medication. She denies unintentional weight loss, blood in the stool, and a family history of colon cancer. She has annual pelvic examinations by her gynecologist and they have been normal. Her physical examination is normal except for a mildly distended lower abdomen which is tender to palpation without rebound. A rectal examination is normal without paradoxical pelvic floor contraction during bear down command. The diagnosis of irritable bowel syndrome with constipation is discussed with the patient. She is reassured that while the symptoms can be debilitating and difficult to treat, they can be managed with appropriate care. Educational materials are given to the patient. After several regular visits with her provider, her symptoms have improved by avoiding certain food triggers and starting lubiprostone. Although her abdominal pain, bloating, and sensation of incomplete evacuation are improved, she continues to be bothered by these symptoms. A low dose of a tricyclic antidepressant as well as a probiotic are recommended.

Management

Assessing severity and impact of the symptoms on the patient’s HRQOL is important, as this will shape a management strategy. Although irritable bowel syndrome is characterized by altered stool frequency and/or consistency, the astute clinician will not assume that the patient seeks care primarily for the relief of these symptoms. Some patients seek care out of fear that they have a life-threatening illness such as colon cancer. These patients may find relief in receiving a positive diagnosis, reassurance, and education and may not require pharmacotherapy. However, patients with moderate to severe symptoms often require pharmacological and/or psychological therapies.

Table Alarm features

Recent symptom onset at age >50 years
Unintentional weight loss
Family history of human gastrointestinal malignancy
Severe, unrelenting large volume diarrhea
Fevers, chills, recent travel to endemic region
Nocturnal diarrhea
Hematochezia
Relevant findings on physical exam (arthritis, skin lesions,
lymphadenopathy, abdominal mass)

Patient-centered Care

A good health-care provider-patient relationship is the cornerstone of effective care of irritable bowel syndrome. The quality of this relationship has been shown to improve patient outcomes. Additionally, addressing psychosocial factors may improve health status and treatment response ,

Non-pharmacologic Therapies

Diet. While in most patients symptoms cannot be completely relieved through diet alterations alone, including elimination diets, diet-related exacerbations can be minimized. Trigger foods may be identified if the patient keeps a food and symptom diary. Common food triggers include high-fat foods, raw fruits and vegetables, and caffeinated beverages.

Psychotherapy and Hypnotherapy. There are several psychological and behavioral treatments for which there is convincing evidence of efficacy. Cognitive-behavioral therapy is a short-term, goal-oriented form of psychotherapy that focuses on the role that thoughts play in determining behaviors and emotional responses. Gut-directed hypnotherapy is hypnosis that is directed towards relaxation and control of intestinal motility by repeated suggestion of control over symptoms followed by ego-strengthening.

Pharmacologic Therapy

Pharmacologic therapies are summarized in Table Agents available to treat irritable bowel syndrome by predominant symptom, which is designed to be a practical clinical reference and includes recommended dosages, pertinent information, and numbers needed to treat where available.

Table Agents available to treat irritable bowel syndrome by predominant symptom

Drug class Generic name Dose Comments
Constipation
Bulking agents Psyllium 1-3tbsp daily First-line for mild-moderate

constipation. Start with 4g/d; gradually

increase over 2-3 weeks to 20-25g/d

Methycellulose 1-3tbsp daily
Polycarbophil 2-4 tablets daily
Osmotic laxatives Milk of Magnesia 1-2tbsp daily-bid
Magnesium citrate 6-12 oz (177-354 mL)
Lactulose 1-2tbsp daily-bid
Polyethylene glycol 17g in 237mL(8oz fluid)
Sorbitol 1-2tbsp daily-bid
Stimulant laxatives Senna 8.6mg tablets; 1-2 tablets qd
Ricinoleic acid (Castor oil) 1-2tbsp daily
Diphenylmethane derivatives (e.g., bisacodyl) 10mg 1-2 tablets qd or 1 suppository qd
Emollient laxatives Docusates 100mg; 1-3 tablets qd
Mineral oil 1tspn-1tbsp qd
5-HT4 agonist Tegaserod 6mg bid Emergency use only
Chloride channel activator Lubiprostone 8mg bid Also available in 24jig for chronic constipation
Diarrhea
Antidiarrheals Loperamide 1 tablet qid Use prophylactically (start at 1/d but

can use up to 8/d)

Diphenoxylate 1-2 tablets tid
Binding agents Cholestyramine 1 g bid to qid
5-HT3 antagonist Alosetron 0.5 mg to 1 mg daily-bid Women with severe irritable bowel syndrome-D, only through restricted use program
Tricyclic antidepressants Amitriptyline 10-150mg qhs Sedating
Doxepin 10-150mg qhs Sedating
Imipramine 10-150mg qhs
Clomipramine 25-100mg qhs
Trimipramine 10-150mg qhs
Desipramine 10-150mg qhs Most evidence for efficacy; less sedation and constipation
Nortriptyline 10-150mg qhs Least sedating
Antibiotics Rifaximin 400 mg tid for 10-14 days
Pain/bloating
Antispasmodics Hyoscamine sulfate 0.125mg sl/po qid prn, May be difficult for some patients to

tolerate due to side effects

0.375 mg po bid
Dicyclomine 10mg po bid
Propantheline

hydrocholoride

15 mg tid ac and 30 mg qhs
Clidinium + chlordiazepoxide 5-1 Omg tid — qid
Hyoscamine +

scopolamine + atropine + phenobarbital

1-2 tablets tid-qid
Tricyclic antidepressants See above
selective serotonin reuptake inhibitors Fluoxetine 10-40mg daily Long half-life; less withdrawal effects
Citalopram 20mg daily Less side effects and drug interactions
Paroxetine 20-50mg daily Short half-life; more withdrawal effects; more anticholinergic effect; use in irritable bowel syndrome-D
Sertraline 25-100mg daily
Escitalopram 10mg daily Less side effects and drug interactions
SNRIs Venlafaxine 37.5-75mg bid-tid Duloxetine is FDA approved for depression and diabetic neuropathy
Duloxetine 40-60mg daily Unlabeled uses include chronic pain

syndromes, fibromyalgia, stress

incontinence

Ongoing open labeled trial for irritable bowel syndrome

5 HT4 agonist Tegaserod See above
Antibiotics Rifaximin 400 mg tid
Probiotics Bifidobacterium infant’s 1 tablet daily
VSL# 3 1 packet bid

Bulking Agents. Bulking agents include psyllium, meth-ykellulose, corn fiber, and ispaghula husk. Fiber supplementation has often been used as initial management of irritable bowel syndrome. Fiber may increase stool frequency in irritable bowel syndrome-C, but this may not be well-correlated with relief of pain or other symptoms. Additionally, bulking agents in quantities that are therapeutic can cause adverse effects including bloating and abdominal pain and discomfort, and therefore it may be helpful to recommend a gradual initiation of the dose to minimize side effects, particularly in those who have relatively little fiber in their diets or those with predominant bloating. Soluble fiber (psyllium, ispaghula, calcium polycarbophil) is more effective than insoluble fiber (corn, wheat bran).

Antidiarrheal Agents. While loperamide appears to be effective at prolonging intestinal transit time and improving stool consistency in irritable bowel syndrome-D, the use of antidiarrheal agents has shown no benefit for global irritable bowel syndrome symptoms or abdominal pain. These agents, which can be used on a regular or an as-needed basis, may be very useful in some irritable bowel syndrome-D patients to manage stool urgency, frequency, and fecal incontinence. It is often useful for patients to use antidiarrheals prophylactically before leaving the house, a long car trip, meal, or a stressful event. This can decrease both the diarrhea during a flare and the anticipatory anxiety often felt by irritable bowel syndrome patients due to the unpredictable nature of symptom exacerbations.

Laxatives. Although no randomized, controlled studies evaluating the efficacy of osmotic or stimulant laxatives have been conducted in irritable bowel syndrome, they may be useful in treating constipation symptoms in those with irritable bowel syndrome-C. Osmotic laxatives are available over-the-counter and are widely used in the treatment of irritable bowel syndrome-C and chronic constipation. Polyethylene glycol or magnesium-containing products are generally safe and well tolerated. Polyethylene glycol can be easily titrated by the patient under the supervision of the physician. Lactulose and sorbitol may also increase stool frequency, but are often associated with the side effects of bloating and/or cramping in irritable bowel syndrome patients. Although there are insufficient data to determine their efficacy in irritable bowel syndrome, stimulant laxatives such as senna, cascara, or bisacodyl may be useful on an intermittent basis for refractory constipation, though frequently cause cramping, loose stools, and urgency.

Antispasmodics. Antispasmodics work by either by a direct effect on intestinal smooth muscle (e.g., mebever-ine, pinaverine) or via their anticholinergic or antimusca-rinic properties (e.g., dicyclomine, hyoscamine). A recent meta-analysis suggests good efficacy for antispasmodics for global relief of irritable bowel syndrome symptoms although most of the studies are not of high quality. An unfavorable side-effect profile, including dry mouth, constipation, urinary retention, and visual disturbances, may preclude treatment at therapeutic doses in some patients.

Serotonergic Agents. Tegaserod is a selective 5HT4 partial agonist that stimulates gut transit and may also have an effect on visceral sensation. Several large and well-designed trials have shown tegaserod to be more efficacious than placebo in improving symptoms of irritable bowel syndrome-C in women. In 2007, tegaserod was suspended and subsequently withdrawn by the FDA based on a small but statistically significant increase in the incidence of cardiovascular ischemic events in patients taking tegaserod compared to those taking placebo (0.1% vs. 0.01%). All of these patients had a history of cardiac disease or risk factors. It is currently only available through the FDA on an emergency basis.

Alosetron is a 5HT3 receptor antagonist that is currently available under a restricted use program and is approved only for women with severe irritable bowel syndrome-D who have failed conventional therapy. This restriction is due to the occurrence of gastrointestinal-related adverse events including ischemic colitis and serious complications of severe constipation. A systematic review concluded that there is a significantly increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15% vs. 0.0%), but no significant difference in the rate of serious complications of constipation. All of the alosetron-using patients with ischemic colitis had a reversible colopathy without long-term sequelae and most cases occurred within the first month of treatment. The restriction notwithstanding, alosetron has been proven efficacious in multiple clinical trials for relief of abdominal pain or discomfort and urgency.

Chloride Channel Activator. In 2008, the chloride channel (C1C-2) activator lubiprostone, which is used to treat chronic idiopathic constipation at a dose of 24μg twice daily, received an FDA indication for irritable bowel syndrome-C in women. Two 12-week, randomized, placebo-controlled trials evaluated the efficacy of lubiprostone at a dose of 8 μg twice daily in patients with irritable bowel syndrome-C. Compared to placebo, lubiprostone was found to significantly improve the secondary endpoints of stool consistency, straining, abdominal pain/discomfort, health-related quality of life (HRQOL), and constipation severity.

Antidepressants. The rationale of using antidepressants in irritable bowel syndrome is that these agents may alter pain perception via a central modulation of visceral afferent input and decreased firing of primary sensory afferent nerve fibers, slow human gastrointestinal transit, and treat of co-morbid psychological symptoms. Tricyclic antidepressants are the best studied in irritable bowel syndrome, and are often used at low doses, because their major impact in irritable bowel syndrome may be more associated with analgesic and motility effects rather than treatment of psychological symptoms. Desipramine and nortriptyline are less sedating than others in the same family such as amitriptyline due to their lower antihistamine effect. If a tricyclic antidepressants is used in irritable bowel syndrome-C, desipramine should be considered since it has less anticholinergic effects and is therefore less constipating than the other Tricyclic antidepressants.

A recent meta-analysis of placebo-controlled trials of selective serotonin reuptake inhibitors in irritable bowel syndrome suggests good efficacy for these agents although most studies have small sample sizes. Selective serotonin reuptake inhibitors have an effect on the physical component of HRQOL, symptom frequency and abdominal pain, and these effects appear to be independent of effects on mood ,

Antibiotics. Small intestinal bacterial overgrowth has been theorized to play a role in irritable bowel syndrome. Rifaximin is an antibiotic which has very low systemic absorption and broad-spectrum activity against Gram-positive and Gram-negative aerobes and anaerobes. In a Phase lib, multicenter, placebo-controlled study, treatment of irritable bowel syndrome-D patients with rifaximin was associated with significantly greater adequate relief of global irritable bowel syndrome symptoms (52% vs. 44%) and bloating (46% vs. 40%) which was maintained at the end of the 12-week follow-up period. Future studies including an ongoing phase III RCT will likely provide more information on the efficacy of this antibiotic treatment in irritable bowel syndrome-D.

Probiotics

Probiotics are hypothesized to work by several mechanisms. These include a shift from a proinflammatory to an anti-inflammatory cytokine profile and enhanced epithelial barrier function. While many species of probiotics subjectively reduced flatulence and bloating, the best evidence for global improvement in irritable bowel syndrome symptoms is for formulations containing species of Bifidobacterium.

Complementary and Alternative Medicine

Because even the most effective treatments for irritable bowel syndrome do not help all patients, many turn to Complementary and Alternative Medicine in search of other treatment options. Additionally, Complementary and Alternative Medicine treatments often provide a more holistic approach and meaningful clinician-patient relationship than western medicine. Acupuncture is popular therapy for irritable bowel syndrome patients. The authors of a recent Cochrane review concluded that acupuncture was likely no better than sham acupuncture, but may have been better than usual care; however, more research is required to make any recommendations. Other alternative or herbal medicines that have been studied are Chinese herbal medicine, peppermint oil, extract of artichoke, carmint, the herbal mixture STW 5, and melatonin.

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