Irritable bowel syndrome : Managing the Patient with Abdominal Pain and Altered Bowel Habits

COMMON MEDICAL PROBLEMS IN AMBULATORY CARE

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IRRITABLE BOWEL SYNDROME Managing the Patient with Abdominal Pain and Altered Bowel Habits Richard B. Lynn, MD, and Lawrence S. Friedman, MD

Abdominal pain and altered bowel habits are nonspecific symptoms that may occur in patients with a wide variety of illnesses. In practice, these symptoms are frequently related to irritable bowel syndrome (IBS). IBS is considered a functional disorder because no specific structural, biochemical, or infectious cause has been found. Although the diagnosis of IBS is often made by excluding organic intestinal diseases, optimal care of the patient may be facilitated by approaching the diagnosis in a positive manner, based in large part on eliciting a characteristic history. One goal of this article is to assist the practitioner in reaching a diagnosis of IBS efficiently by using a carefully obtained history, physical examination, and appropriate laboratory tests. With this approach, it may be possible to keep diagnostic testing to a minimum, thereby reducing the risk and cost to the patient. In addition, making a positive diagnosis of IBS can have important therapeutic benefit. IBS is likely a heterogeneous group of disorders. Numerous studies have demonstrated altered gastrointestinal motility or abnormal visceral sensation in patients with IBS. Although none of the findings is present in all patients, it is possible that there are subgroups of patients for whom the reported findings are characteristic. In addition, psychosocial factors have important effects on the clinical expression of IBS. Another goal of this article is to make the practitioner aware of advances in This work was supported in part by Grant No. DK02094 from the National Institutes of Health. From the Department of Medicine, Jefferson Medical College, Thomas Jefferson University (RBL), Philadelphia, Pennsylvania; Harvard Medical School (LSF); and Gastrointestinal Unit, Massachusetts General Hospital (LSF), Boston, Massachusetts MEDICAL CLINICS OF NORTH AMERICA VOLUME 79 • NUMBER 2 • MARCH 1995

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understanding of pathophysiologic and psychosocial processes in IBS so that treatment may be tailored to an individual patient's needs. DEFINITION AND CLINICAL PRESENTATION

Patients with IBS present with a broad range of complaints wellknown to most clinicians. Symptoms may be continuous or intermittent but should be present for at least 3 months before the diagnosis of IBS is considered. The most common presentation is with abdominal pain associated with altered bowel habits, specifically constipation, diarrhea, or alternating constipation and diarrhea. 10 A less common presentation is with painless diarrhea,lO which has been presumed to be a variant of IBS. Recommendations to define the syndrome more rigorously require the presence of both abdominal pain and altered bowel habits (Table 1).21,89 These more rigorous definitions are important for standardizing research in this field but may not be relevant to the care of the individual patient. Similarly, abdominal pain without altered bowel habits, although not considered to be part of the spectrum of IBS, may be closely related. Chronic constipation without abdominal pain is generally considered to be a separate disorder. Particularly useful observations regarding identification of patients with IBS were made by Manning and colleagues,56 who found that six symptoms were more common in IBS than in other gastrointestinal diseases considered to be organic: 1. 2. 3. 4. 5. 6.

Pain relief with bowel action. More frequent stools with the onset of pain. Looser stools with the onset of pain. Passage of mucus. Sensation of incomplete evacuation. Abdominal distention as evidenced by tight clothing or visible appearance.

Subsequent studies have confirmed the usefulness of these six symptoms in supporting a diagnosis of IBS.37, 86 Talley and associates 86 reported one additional symptom that had predictive value in IBS: stools that are loose and watery more than 25% of the time. The likelihood of IBS increases as the number of the so-called Manning criteria increases. 56, 86 For example, among 20-year-old women, 92% had IBS when all six symptoms were present compared with only 64% when two symptoms were present. 86 The predictive ability of the six criteria diminishes with increasing age; for example, among 60-year-old women, 80% had IBS when all six symptoms were present compared with only 38% when two symptoms were present. 86 In general, the Manning criteria are less useful in men than in women?8, 86 The clinical features of IBS include symptoms other than those referable to the lower gastrointestinal tract. Patients with IBS are more likely than controls to have gastroesophageal reflux and other symptoms

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Table 1. DIAGNOSTIC CRITERIA FOR IRRITABLE BOWEL SYNDROME

At least 3 months of continuous or recurrent symptoms of: Abdominal pain or discomfort that is Relieved with defecation, Associated with a change in frequency of stool, or Associated with a change in consistency of stool and Two or more of the following, at least on one fourth of occasions or days Altered stool frequency (for research purposes, altered may be defined as more than three bowel movements each day or less than three bowel movements each week) Altered stool form (lumpy/hard or loose/watery stool) Altered stool passage (straining, urgency, or feeling of incomplete evacuation) Passage of mucus Bloating or feeling of abdominal distention From Thompson WG, Drossman DA, Funch-Jensen P, et al: Functional bowel disorders and functional abdominal pain. In Drossman DA, Richter JE, Talley NJ, et al (eds): The Functional Gastrointestinal Disorders. Boston, Little, Brown and Company, 1994, p 120; with permission.

referable to the upper gastrointestinal tract, such as heartburn, dysphagia, globus sensation/7 and noncardiac chest pain. 7o Patients with IBS may also have a broad range of nongastrointestinal symptoms, such as fatigue, urologic dysfunction, and gynecologic complaints. 107 EPIDEMIOLOGY

Gastrointestinal symptoms are common, occurring in more than one third of adults. In questionnaire studies, symptoms compatible with IBS are reported by 10% to 22% of adults in the general population, with a slight female predominance. 22 • 35, 39, 87 The prevalence of IBS is similar in elderly and younger adults,67, 84 although the onset of symptoms is typically in young adulthood. It is a worldwide disorder affecting persons in both industrialized and nonindustrialized countries; for example, a Chinese survey reported a prevalence of functional gastrointestinal symptoms similar to that in Western countries. 3 Of adults with symptoms of IBS, only 14% to 50% actually seek medical attention. 22 , 35, 39, 87 The reason some patients with IBS seek medical attention and others do not has become an important area of investigation and is not accounted for by the number and severity of symptoms but appears to be related to psychosocial factors (see later).39,87 Patients presenting with symptoms of IBS represent an extraordinarily large group, constituting up to 25% to 50% of outpatient referrals to gastroenterologists. 24 ,50 PATHOPHYSIOLOGY

Numerous studies have demonstrated motility or sensory abnormalities in the colon, rectum, or small bowel of patients with IBS, as reviewed recently.33, 51, 60,61 Unfortunately, none of the reported findings

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is sufficiently sensitive or specific to serve as a diagnostic marker of IBS. A fundamental problem with most of the reported studies is that the pain of IBS is typically intermittent, but laboratory investigation of patients is usually performed at a single point in time, when patients may not be experiencing abdominal pain. Moreover, abnormalities in intestinal motility or sensation (or the lack of abnormalities) at baseline or in response to an artificial stimulus may not be relevant to the symptomatic patient with IBS and spontaneously recurring abdominal pain. Continuous recording methods may be required for optimal study of patients with IBS. IBS is often assumed to be caused by altered colonic motility because many of the characteristic symptoms identified by Manning and colleagues56 are attributable to colonic dysfunction and because the pain of IBS is frequently located in areas referable to the colon.· An early report by Snape and coworkers79 described an increase in three-cydeper-minute slow-wave activity (associated with nonpropulsive segmenting contractions) in the distal colon and rectum of patients with IBS as compared with normal controls; however, this finding has not been confirmed by all investigators. Alterations in colonic motility in response to stimuli such as eating,66, 80 anger,95 and psychological stress9h, 103 have been reported more consistently in patients with IBS. These studies, however, have employed acute models of stress, which may not be relevant to the chronic life stresses reported by patients with IBS. Attention has focused on the role of the ascending colon in the pathophysiology of IBS. In one study,9 the onset of pain, particularly in the right lower quadrant, was associated with the arrival of the test meal in the cecum in 74% of patients. In another study,93 patients with diarrhea-predominant IBS were found to have accelerated transit through the proximal colon, presumably resulting in impaired intestinal absorption of water. The relevance of these findings to the pathophysiology of IBS remains to be determined. Motility of the small intestine has been studied with continuous recording techniques. Several studies have reported an increase in hypercontractile events in the fasting state in some patients with IBS,42, 44, 45 and in some cases hypercontractile events were associated with spontaneous abdominal pain. 45 A recent study, however, did not confirm these findings. 27 Altered visceral sensation has received much attention and has proved to be a reproducible finding in patients with IBS. Lasser and associates 49 originally reported that although patients with IBS do not have increased intestinal gas, they experience abdominal pain at intestinal gas volumes that are lower than those that cause pain in healthy controls. Studies have demonstrated further that balloon distention in the sigmoid colon/I, 104 rectum,69 and small intestine 46 in patients with IBS results in pain at volumes that usually are not painful to controls. Detailed analysis of these studies suggests that in patients with IBS the lower pain threshold in response to gut distention is due to altered

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visceral pain sensation,59 even though patients with IBS actually have a higher threshold for pain in response to somatic pain stimuli, such as electrocutaneous stimulation13 or hand immersion in ice water.1ll4 Interestingly, patients with IBS also have been found to have an enhanced perception of nonpainful physiologic intestinal motility eventsY Presumably, altered visceral sensation in patients with IBS is related to abnormal central nervous system transmission and modulation of pain sensation, although it could be the result of an abnormality in the gut. A study describing decreased [3-endorphins in the cerebrospinal fluid of patients with functional abdominal pain (but without altered bowel habits) suggests a possible mechanism for central nervous system dysfunction in IBS.40 Other pathophysiologic processes in IBS have been suggested but remain unproven. For example, neuroimmune mechanisms ll could mediate stress-induced gastrointestinal responses, bile acid malabsorption by the terminal ileum could result in altered fluid secretion and motility in the colon or rectum,23, 63 and increased numbers of mast cells in the terminal ileum in patients with IBS could cause local release of histamine and enhanced visceral sensation.'!? IBS appears to be closely related to other functional disorders of the gastrointestinal tract, such as chest pain of unexplained origin, nonulcer dyspepsia, and biliary dyskinesia. Similar pathophysiologic findings have been described in all of these disorders. It is possible that these functional disorders share the same underlying pathophysiology, but that the clinical presentation depends on the specific site in the gastrointestinal tract that is affected. There is also evidence that the clinical spectra of these disorders overlap. For example, patients with IBS have a lower pain threshold to esophageal balloon distention 14 and are more likely than controls to have noncardiac chest pain?O Similarly, patients with chest pain of unexplained origin frequently have symptoms compatible with IBS/G,76 and functional dyspepsia has been shown to coexist frequently with IBS.15 IBS may even be a part of a more generalized disorder affecting pulmonary98 and urologic106, 107 function.

PSYCHOSOCIAL FACTORS

Psychosocial factors have been found to play an important role in the clinical expression of IBS. Patients presenting with IBS have an increased prevalence of psychiatric diagnoses,4, 20, 75, 101 including personality disorders, anxiety, depression, hysteria, and somatization, although at least one study reported a lack of significant psychopathology in patients with IBS.sS Conflicting reports may be reconciled by the observation that patients presenting to a physician with symptoms of IBS have a higher frequency of psychological disturbances than persons with symptoms of IBS who do not seek medical attention. 18, 100 In fact, persons with symptoms of IBS who do not seek medical attention are not significantly different psychologically from healthy subjects. Therefore,

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although psychosocial factors do not cause the symptoms of IBS, they influence how the illness is experienced and acted on by the patient. Although presenters also report more severe gastrointestinal distress than nonpresenters, it remains unclear whether they actually experience more pain or merely report their pain as more severe. Indeed, the presence of psychosocial dysfunction predicts presentation to a physician independently of the reported severity of symptoms, and patients with IBS are more likely to seek medical attention for nongastrointestinal as well as gastrointestinal problems?3 Whitehead and Crowell101 have hypothesized that patients with IBS who seek medical attention have a learned illness behavior originating in childhood experiences. In particular, recent observations suggest that patients with IBS are more likely than controls to have a history of childhood sexual or physical abuse (or both)Y' 53, 74, 94 Moreover, when compared with nonabused patients, patients with IBS and a history of abuse have a lower pain threshold as well as greater frequency of psychiatric disorders?4 Often a history of sexual or physical abuse is not reported by the patient to the physicianY Stress is known to cause exacerbations of bowel symptoms in a majority of patients with IBSlO, 19 as well as in healthy subjects. 19 Stressful life events have been reported to be more frequent in patients with IBS,62,102 but other reports have disputed this finding. IS In fact, a review of emotional stress and gut dysfunction concluded that despite extensive investigation, a definite link between stress and IBS remains unproven? The mechanism of a possible brain-gut connection mediating the effects of stress on intestinal function has not been defined, although the vagus nerve is the likely conduit via a discrete population of vagal motor and sensory neurons innervating the cecum2 and colon. 1 EVALUATION

The goal of the initial evaluation of the patient presenting with chronic abdominal pain and altered bowel habits and presumed to have IBS is to establish a positive diagnosis of IBS based on characteristic symptoms and to exclude other potential causes by thorough history taking and physical examination. The presence of the specific symptoms described by Manning and associates 56 (see earlier under Definition and Clinical Presentation) is useful in supporting the diagnosis of IBS, especially in young women. If the diagnosis of IBS is made by exclusion, an expensive evaluation that is unnerving to the patient may ensue. Anxiety and insecurity may be fostered by an exhaustive search for specific diagnostic findings to account for the symptoms, adding to the fear that something may be missed and the belief that symptomatic relief depends on finding a specific underlying abnormality. Clearly, physician and patient insecurity are minimized by approaching the diagnosis in a positive manner. 88 A detailed description of the abdominal pain and bowel habits

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should be obtained, but wide variations in these symptoms are compatible with IBS. The pain is most often located in the lower abdomen but may occur in any quadrant. Balloon distention throughout the colon of patients with IBS and normals has been shown to cause pain perceived in any abdominal site, although lower abdominal sites are most common. 83 A careful description of bowel frequency, consistency, and volume should be elicited, but it is important not to accept the patient's conclusion that he or she has diarrhea or constipation because bowel habits have a wide range of normal. Any significant change from the individual's customary pattern may be significant. Voluminous diarrhea is unusual in IBS and suggests either malabsorption or a secretory diarrhea. Greasy, foul-smelling stools that are difficult to flush suggest malabsorption. The sensation of incomplete evacuation is often described by patients with IBS as a feeling of constipation leading to multiple attempts at stool passage. Incomplete evacuation may be difficult to distinguish from mild tenesmus owing to proctitis. Some patients complaining of incomplete evacuation actually have otherwise normal bowel habits; these patients seem to have a sensory or perhaps psychological disorder but erroneously report constipation leading to abuse of cathartics, even to the point of inducing diarrhea. The cycle may be broken (after excluding rectal inflammation) by convincing the patient that the sensation is erroneous and that the rectum is in fact empty. Careful history taking should also serve to exclude symptoms incompatible with IBS and suggestive of organic disease (Table 2), such as abdominal pain or diarrhea that awakens the patient from sleep, visible or occult blood in the stool, weight loss, or fever. Panic disorders often present with gastrointestinal symptoms suggestive of IBS and are important to recognize because they may be amenable to specific therapy.41,54 A complete list of medications used by the patient should be elicited because numerous medications can cause diarrhea or constipation (Table 3). Causes of chronic diarrhea are shown in Table 4. A dietary history is important, and the patient should be questioned specifically about symptoms suggestive of lactose intolerance, which can cause symptoms that mimic IBS but which should not be considered a cause of IBS. A 3-week trial of a lactose-free diet is a useful way to exclude lactose intolerance as a cause of the symptoms. Alternatively, a hydrogen breath test following ingestion of lactose may be considered in confusing cases. Excessive use of foods, beverages, or medications sweetened with fructose or sorbitol also can cause gastrointestinal symptoms as a result of malabsorption,38, 72 Other diagnoses that can be confused with IBS should be considered carefully: L Colonic adenocarcinoma, villous adenoma. 1. Crohn's disease, ulcerative colitis. 3, Ischemic colitis, chronic mesenteric vascular insufficiency. 4. Chronic idiopathic intestinal pseudo-obstruction. 5. Fecal impaction, intermittent sigmoid volvulus, megacolon. 6. Giardiasis. 7. Lactase deficiency (lactose intolerance). 8. Endometriosis. 9. Depression, somatization, anxiety, panic disorders.

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Table 2. SUGGESTED EVALUATION OF PATIENTS WITH SYMPTOMS OF IRRITABLE BOWEL SYNDROME History Presence of typical symptoms for at least 3 months Identify Manning criteria (see text)56 Exclude symptoms suggestive of organic disease Pain that awakens patient from sleep Pain that interferes with normal sleep patterns Diarrhea that awakens patient from sleep Visible or occult blood in the stool Weight loss Fever Dietary history to exclude lactase insufficiency or excessive use of sorbitol, fructose, or aspartame Review medications for gastrointestinal side effects (see Table 3) Identify psychosocial factors precipitating presentation Consider depression or panic disorders Physical Examination Should be unremarkable; significant findings require further evaluation Laboratory Examination Complete blood count, erythrocyte sedimentation rate, chemistry panel Flexible sigmoidoscopy If diarrhea-predominant Examination of stool for ova and parasites, fecal leukocytes, excessive fat Thyroid function tests Sigmoidoscopic biopsies Adapted from Lynn RB, Friedman LS: Irritable bowel syndrome. N Engl J Med 329:1942, 1993; with permission.

Table 3. MEDICATIONS THAT COMMONLY CAUSE DIARRHEA OR CONSTIPATION Diarrhea*

Constipation

Antacids containing magnesium Antibiotics Colchicine Digoxin Guanethidine Lactulose Loop diuretics Propranolol Quinidine Theophylline Thyroxine

Antacids containing aluminum or calcium Anticholinergics Anticonvulsants Diuretics Ganglionic blockers Iron supplements Opiate analgesics Monoamine oxidase inhibitors Phenothiazines Parkinsonism drugs Tricyclic antidepressants

*Many medications contain sorbitol, which can cause diarrhea; for a complete list of such medications, see Johnston et al. 38

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It may be useful to determine the precipitating factor, such as a major life stress, that has prompted the patient to seek medical attention. Consideration should be given to the possibility of a psychological disturbance, as discussed previously.20 The possibility of childhood or sexual abuse may need to be explored in selected patients. Because these issues are sensitive, they may need to be addressed in subsequent visits after a solid physician-patient relationship has been established. The physical examination in IBS is generally unremarkable. Nevertheless, the "laying on of hands" and reassurance that the physical examination is normal can have therapeutic value. Abdominal tenderness may be detected but is typically unimpressive. Findings such as a mass lesion, lymphadenopathy, hepatosplenomegaly, jaundice, ascites, or a positive fecal occult blood test are incompatible with the diagnosis of IBS alone and require further evaluation. Routine laboratory studies are generally normal in IBS but may help exclude a number of "organic" diseases. A reasonable evaluation includes a complete blood count, erythrocyte sedimentation rate, and chemistry panel. If diarrhea is the predominant symptom, stool examination for enteric pathogens, ova and parasites, and fecal leukocytes as well as thyroid function tests should be obtained. A stool collection may be useful because stool weight in excess of 300 g per day or the detection of excessive fecal fat are unlikely in IBS. Flexible sigmoidoscopy is generally included in the evaluation of IBS in all patients over age 40 to exclude colonic neoplasms and in younger patients with persistent diarrhea to exclude inflammatory

Table 4. CAUSES OF CHRONIC DIARRHEA

Dietary factors Lactase deficiency (lactose intolerance) Excessive intake of food or beverages with sorbitol or fructose Infections Giardiasis, amebiasis Opportunistic infections associated with the acquired immunodeficiency syndrome Inflammatory bowel disease Crohn's disease or ulcerative colitis Malabsorption Small bowel diseases: celiac disease, Whipple's disease, short bowel syndrome Pancreatic insufficiency Bacterial overgrowth Metabolic Addison's disease, diabetes, hyperthyroidism Collagenous or lymphocytic colitis Postgastrectomy and other postsurgical syndromes Fecal impaction Diverticulitis Laxative abuse Tumors Colon cancer, villous adenoma Gastrinoma, carcinoid, VIPoma, medullary carcinoma of the thyroid

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bowel disease. Any abnormalities, such as friable mucosa, ulceration, or mass lesions, are incompatible with the diagnosis of IBS alone. In patients with persistent diarrhea, sigmoidoscopic biopsies should be performed to exclude collagenous or lymphocytic colitis. Sigmoidoscopic biopsies in patients with other symptom complexes suggestive of IBS (e.g., alternating diarrhea and constipation), however, have a low diagnostic yield and are probably not cost-effective. 55 A barium enema or colonoscopy is generally not needed in the evaluation of patients with suspected IBS but should be considered if the patient is over age 40 or if there is a strong family history of colorectal neoplasms. Symptoms suggestive of upper gastrointestinal or biliary tract disease should be evaluated with appropriate barium, endoscopic, or ultrasonographic studies.

MANAGEMENT The most important component of the treatment of IBS is establishing a therapeutic physician-patient relationship. In an authoritative review focusing on the biopsychosocial aspects of managing IBS, Drossman and Thompson2o have emphasized the importance of a relationship that is nonjudgmental, is concerned with the patient's understanding of his or her illness, establishes realistic expectations and consistent limits, and involves the patient in treatment decisions. The chronic nature of the illness requires a long-term relationship, which is best established with the primary care physician. Consultants may be needed in selected cases to help confirm the diagnosis, suggest or reinforce treatment strategies, or address significant psychosocial disturbances, especially when there has been a breakdown in the physicianpatient relationship. Armed with a confident positive diagnosis, the physician should begin by explaining that the patient's symptoms are common and that the prognosis is excellent. The patient should be told that IBS is a benign disorder that does not progress to, or increase the risk of, any other disease. Often, it is particularly helpful to emphasize to the patient that he or she does not have cancer. Improving the patient's understanding of the origin of the symptoms with an oversimplified explanation of bowel motility may also be helpful. It is important to establish realistic expectations; there is no cure for IBS, but there are some steps the physician and patient can take to improve the symptoms, and the patient should be involved in treatment decisions. The earlier in the process these reassurances are provided, the more effective they will be. A second visit shortly after the laboratory evaluation is complete is an opportunity to confirm the positive diagnosis of IBS and to restate the aforementioned explanations and assurances. This second visit also reinforces to the patient that the physician will work with him or her on an ongoing basis. After this second visit, it is usually possible to lengthen the time between visits, especially if the patient knows the physician is available when needed.

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Initial therapeutic recommendations to the patient generally focus on dietary modifications that may lessen symptoms. These include the avoidance of certain foods, such as dairy products; foods, beverages, or medications sweetened with fructose or sorbitoPS, 72; or other gas-forming foods such as legumes. Emphasis is often placed on fiber supplementation, although the efficacy of this treatment has not been proven, in part because of a high placebo response rate (63% to 71 %) for any drug used to treat IBS.12, 47, 52 A literature review by Muller-Lissner 64 found that wheat bran increases stool weight, hastens gut transit, and is likely to improve constipation in patients with constipation-predominant IBS. One study found, however, that in 55% of patients with IBS, symptoms actually worsened with bran, whereas in only 10% did symptoms improve. 25 The authors of this study even raised the question of whether fiber supplementation should be abandoned in the treatment of IBS. Clinical experience suggests, however, that although some patients do not tolerate fiber supplements, others may experience bloating and discomfort for the first few weeks but benefit thereafter. Synthetic fiber supplements, such as polycarbophil, methylcellulose, and psyllium, are more soluble than natural fibers, but whether they cause less bloating or are more effective than natural fiber supplements has not been determined. One study 91 found polycarbophil to be effective in patients with IBS and alternating diarrhea and constipation as well as in most IBS patients with constipation alone. Because of its safety and large placebo response, a trial of fiber seems reasonable in all patients with IBS. Most patients with IBS improve with the simple measures just outlined. In one study, most patients responded to treatment, and two thirds remained symptom-free after 5 years. 32 A large number of patients, however, continue to complain of symptoms. 31 , 36, 82 Further diagnostic investigation is often undertaken in these chronic patients, although it rarely leads to successful therapy. A number of medications are frequently used to treat IBS (Table 5), but in a review of the literature on drug therapy of IBS, Klein 47 concluded that "not a single study offers convincing evidence that any therapy is effective in treating the IBS symptom complex." Inability to prove efficacy, however, was due mostly to poor study design, small numbers of subjects, and large placebo responses, not necessarily to the lack of efficacy of the medications. Certainly an individual patient may benefit from one of the frequently prescribed medications, if only because of its placebo effect. A shotgun, trial-and-error approach to the medical therapy of IBS is to be discouraged, in great part because of its potential to mislead the patient into believing there is a "magic-bullet" cure, if only it can be found. Camilleri and Prather8 have recommended a pathophysiologic approach based on alleviating the predominant symptom. For example, in patients with diarrhea-predominant IBS, an antidiarrheal agent (e.g., loperamide, diphenoxylate) may be recommended, whereas in patients experiencing pain-gas-bloat symptoms, antispasmodic agents such as anticholinergics (e.g., belladonna, dicyclomine) may be tried.

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Table 5. MEDICATIONS FOR IRRITABLE BOWEL SYNDROME (IBS) Drug Type and Examples (Suggested Starting Dose) Fiber supplements Wheat bran ('12 cup to 1 bowl qd, 10-30 9 qd) Psyllium ('12 to 1 tbsp qd to bid) Ispaghula48 (20 9 qd) Antispasmodics (anticholinergics) Tincture of belladonna (5-10 drops po tid) Dicyclomine (10-20 mg tid-qid) Cimetropium bromide '6 (50 mg tid) Antidiarrheals Diphenoxylate (2.5-5 mg qid) Loperamide (2 mg bid) Cholestyramine ('12-1 pck qd-bid) Tricyclic antidepressants Amitriptyline (10-25 mg qhs) Desipramine (50 mg qhs) Prokinetic agents Cisapride (5-10 mg tid) Domperidone (10-20 mg qid) Benzodiazepine-type anxiolytics Somatostatin agonists Calcium channel-blockers Gonadotropin-releasing hormone analogs Serotonin receptor antagonists

Indications Constipation-predominant IBS: may be tried for any IBS symptom complex

Pain-predominant IBS; prevention of predictable postmeal abdominal pain

Diarrhea-predominant IBS

Pain-predominant IBS; chronic pain syndrome Constipation-predominant IBS Anxiety, use for brief periods Experimental Experimental Experimental Experimental

Adapted from Lynn RB, Friedman LS: Irritable bowel syndrome. N Engl J Med 329:1943, 1993; with permission.

Anticholinergics are the most frequently used medications for the treatment of ms. Side effects are dose related: The lowest doses may have no side effects; low doses decrease salivary and bronchial secretions and sweating; and large doses cause pupillary dilation, tachycardia, and perhaps urinary retention. Newer anticholinergics (e.g., dicyclomine, cimetropium bromide 16 ) are purported to act selectively on gastrointestinal smooth muscle and may have fewer side effects than nonselective anticholinergics. Anticholinergics may have a direct inhibitory effect on the gastrocolic reflex, and for patients with predictable abdominal pain after meals, these agents may be taken before meals to have their maximum effect at the time of expected symptoms. 33,90 Tricyclic antidepressants have proved useful in a number of chronic pain syndromes and have been tried in patients with pain-predominant mS. 28 ,65 Whether a response to these drugs relates to their anticholinergic or antidepressant effects or to a direct effect on pain perception is unclear. 20 Although the antidepressant effects of tricyclic agents generally require 6 to 8 weeks to occur, the anticholinergic and analgesic effects occur within 24 to 48 hours. Tricyclics should be used cautiously in patients with heart disease and in the elderly. Anxiolytic agents are not indicated in most patients with ms but

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may be used for brief periods in the treatment of episodic stress-related exacerbations of IBS.20 Benzodiazepines can cause drowsiness and impaired judgment and coordination. In addition, they can be habit forming and may have a rebound effect on withdrawal. Buspirone, a newer agent, may cause less impairment of intellectual or motor performance than other benzodiazepines. 26 A number of other medications have been considered for use in IBS. In one study,92 treatment with the pro kinetic agent cisapride resulted in improvement in constipation and abdominal pain in patients with constipation-predominant IBS. Because calcium channel-blockers relax gastrointestinal smooth muscle, they have been suggested as a treatment for IBS but have not been studied adequately. The somatostatin analog octreotide inhibits sensitivity to rectaP4 and colonic" balloon distention in patients with IBS, in addition to its effects on gastrointestinal motility and secretion, but has not been studied adequately in clinical trials. Serotoninergic neurons influence colonic motility and sensation and are important in central nervous system modulation of pain sensation, and selective serotonin receptor antagonists have a potential but unproven future in the treatment of IBS. Cholestyramine, which binds intestinal bile salts, may be helpful in some patients with diarrhea-predominant IBS.8 Initial studies of gonadotropin-releasing hormone analog (leuprolide acetate) in the treatment of functional bowel disorders have been promising,57, 58 but results in patients with well-defined IBS have not yet been reported. Alternative therapies have been demonstrated to be efficacious in some, often selected patients with IBS. These include psychotherapy/9, 30, 81 hypnotherapy,68, J05 and biofeedback,99 alone or in combination. 5 Referral to a psychiatrist is appropriate for patients believed to have significant psychiatric illness, but further studies are needed before these alternative therapies can be recommended more widely. Brief psychotherapy or counseling, within the capability of any concerned physician, is likely to be worthwhile in many patients with IBS.88 The content of this interaction, as emphasized elsewhere in this article, should focus on confirmation of the diagnosis, reassurance, an exploration of issues that may have prompted the patient to seek medical attention, and strategies to reduce stress in the patient's life. Patients with IBS can be demanding with their repeated insistence on further testing and treatment. The physician must keep in mind that the prognosis of IBS in terms of life expectancy or major morbidity is excellent. Moreover, diagnostic testing and therapeutic trials can result in complications and side effects. Efforts are best directed toward firm and empathetic psychosocial support in the context of a sustained physician-patient relationship. References 1. Altschuler SM, Escardo J, Lynn RB, et al: The central organization of the vagus nerve innervating the colon of the rat Gastroenterology 104:502, 1993

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