Irritable bowel syndrome: a practical review.Abstract: The epidemiology and current understanding of the pathophysiology pathophysiology /patho·phys·i·ol·o·gy/ (-fiz?e-ol´ah-je) the physiology of disordered function. path·o·phys·i·ol·o·gy n. 1. of irritable bowel syndrome irritable bowel syndrome (IBS), condition characterized by frequently alternating constipation and diarrhea in the absence of any disease process. It is usually accompanied by abdominal pain, especially in the lower left quadrant, bloating, and flatulence. is reviewed, beginning with a historical perspective. The roles of genetics, environment, allergy, infection and inflammation, bacterial overgrowth bacterial overgrowth GI disease The multiplication of opportunistic bacteria in the lower GI tract, often due to antibiotic therapy. See Pseudomembranous colitis Lab medicineThe multiplication of contaminating bacteria in a specimen–eg, blood, urine, due to , hormones and motility motility /mo·til·i·ty/ (mo-til´ite) the ability to move spontaneously.mo´tile Motility Motility is spontaneous movement. abnormalities are discussed. Using the current evidence-based literature, the practical approach of diagnosis and treatment is outlined, including traditional modalities and newer therapeutic agents such as serotonin modulators. Key Words: irritable bowel syndrome, functional bowel disorder In medicine, the term functional bowel disorder refers to a group of bowel disorders which are characterised by chronic abdominal complaints without a structural or biochemical cause that could explain symptoms. , diarrhea, constipation Irritable bowel syndrome (IBS IBS Irritable bowel syndrome, see there ) comprises a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation defecation or bowel movement Elimination of feces from the digestive tract. Peristalsis moves feces through the colon to the rectum, where they stimulate the urge to defecate. or a change in bowel habits, and has features of disordered defecation. (1) The diagnosis is based on a series of symptom criteria and limited investigations to exclude organic disease. The effort of defining IBS based on clinical symptoms resulted in the 1978 Manning criteria (Table 1). Manning et al (2) presented the first set of criteria based on a study comparing 32 patients with IBS and 33 patients with organic disorders. His criteria, very popular with the clinicians, were followed in 1984 by Kruis (3) criteria, which are not as frequently used by clinicians (Table 2). The Kruis criteria, together with Manning criteria, represent the basis for the contemporary Rome criteria. In 1992, the first Rome criteria were published and readily incorporated into research but were considered too cumbersome for clinical use. The revised criteria, published in 2006, were created to improve the clarity and internal consistency and reflect the new research data. (1) In Rome II criteria (see Table 3), the frequency of symptoms is further refined and the subtypes of IBS by predominant stool pattern are clarified. Abdominal distention dis·ten·tion or dis·ten·sion n. The act of distending or the state of being distended. distention, n a state of dilation. is no longer considered a diagnostic criterion. In subsequent analyses, Rome II proved to be more sensitive than Rome I in identifying women with IBS. (1) Further validation of Rome III is awaited. Epidemiology The prevalence of IBS is considered to be between 9 to 22% in the US, and 4 to 35% worldwide. (4-6) In the US it accounts for 12% of primary care provider visits and 28% of visits to the gastroenterologist. (7-9) The direct and indirect costs from IBS are estimated to be between 15 and 30 billion dollars per year (estimated 8 billion only for healthcare costs). (10,11) IBS incidence peaks in the third and fourth decade of life and decreases in the sixth and seventh. The diagnosis of IBS is based on the interpretation of clinical criteria, and the prevalence is influenced by social and cultural factors. What is considered disease and the reasons for seeking medical attention varies with populations, and this may explain the differences in the prevalence of IBS worldwide: IBS is as common in China as in the western countries, but less common in Thailand. (1) In South African rural areas, IBS is not as common when compared with the cities. (1) There is a female predominance in the western world, where women are 3 to 4 times more likely than men to be diagnosed with IBS, but females represent only 20 to 30% of IBS patients in India and Sri Lanka. (1) Race does not appear to be a factor; the prevalence is similar in whites and blacks. Once IBS is diagnosed, 75% of patients remain symptomatic 5 years later. (12) Understanding IBS The symptom association that defines IBS has been described by physicians starting in the 19th century. (13) Most of the major current hypotheses for the etiology and pathophysiology of IBS appear to have been formulated before the 1950s: hormonal influences, (14) food intolerance food intolerance Nutrition Food sensitivity An adverse reaction to specific foods, seen in ±10% of the population, which are often chronic and may cause severe illness; FI is not synonymous with food allergies, which are predictable, often severe, involve , (15) postinfectious, (14) and hypersensitivity hypersensitivity, heightened response in a body tissue to an antigen or foreign substance. The body normally responds to an antigen by producing specific antibodies against it. The antibodies impart immunity for any later exposure to that antigen. . (16) In the last 15 years, human physiologic studies and more rigorous randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. control trials (RCTs) have focused upon substantiating many of these clinical observations on a pathophysiological basis, in an attempt to separate cause from effect. Hypothesis for the Etiology and Pathophysiology of IBS Motility Disturbance Studies of gastrointestinal motility showed different patterns of abnormal motility in patients with IBS, but none have proven to be pathognomonic pathognomonic /pa·thog·no·mon·ic/ (path?ug-no-mon´ik) specifically distinctive or characteristic of a disease or pathologic condition; denoting a sign or symptom on which a diagnosis can be made. ; delayed or accelerated migrating motor complexes migrating motor complexes regularly occurring motor complexes are recorded in the intestine of turkeys and chickens. (MMCs) and high amplitude propagating contractions within the colon have been found. (17-19) Hormonal Hypothesis The hypothesis of estrogen involvement in the etiology of IBS is raised by clinical observations that IBS is more likely to be found in women and reports of symptom exacerbation during the menstrual cycle menstrual cycle n. The recurring cycle of physiological changes in the uterus, ovaries, and other sexual structures that occur from the beginning of one menstrual period through the beginning of the next. by some patients. Mathias et al (20-22) found significant improvement of abdominal pain in functional bowel disorders by inhibition of hypothalamopituitary-ovarian axis with leuprolide acetate leu·pro·lide acetate n. A synthetic polypeptide analog of naturally occurring gonadotropin-releasing hormone used in the treatment of advanced prostate cancer. . In a case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. , hormone replacement therapy Hormone Replacement Therapy Definition Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body. is associated with an increased risk of IBS. (23) Heitkemper et al (24) followed the symptom profile of IBS and controls across the menstrual cycle and found the IBS group to have not only more GI symptoms, but also more somatic and menstrual symptoms. They found the pattern of IBS symptoms over the menstrual cycle to be no different in patients when compared with normal controls. (24) Role of Genetics and Environment Two different twin studies have shown higher concordance concordance /con·cor·dance/ (-kord´ins) in genetics, the occurrence of a given trait in both members of a twin pair.concor´dant con·cor·dance n. for IBS in monozygotic monozygotic /mono·zy·got·ic/ (mon?o-zi-got´ik) pertaining to or derived from a single zygote; as monozygotic twins. mon·o·zy·got·ic adj. than in dizygotic twins dizygotic twins Fraternal twins Twins resulting from 2 separate fertilized eggs, liberated simultaneously from the ovaries, which develop in separate or partially fused chorion and placenta, and usually a separate amniotic sac. Cf Monozygotic twins. . (25,26) On the other hand, Lembo et al found the concordance rate concordance rate n. A quantitative statistical expression for the concordance of a given genetic trait, especially in pairs of twins in genetic studies. for IBS symptoms to be similar in monozygotic and dizygotic twins. There is probably a genetic component, although other environmental factors are also required. Parental rejection, parental history of somatization disorder somatization disorder n. A disorder characterized by an individual's seeking help for and acquiring a complicated medical history of multiple physical symptoms referring to a variety of organ systems, but for whose complaints there is no detectable , and history of abuse are associated with higher risk of IBS. (27-29) Bacterial Overgrowth The role of bacterial overgrowth is controversial. Symptoms of bacterial overgrowth are similar with symptoms of IBS. Pimantel et al (30,31) reported a high likelihood of abnormal lactulose lactulose /lac·tu·lose/ (lak´tu-los) a synthetic disaccharide used as a laxative and to enhance excretion or formation of ammonia in the treatment of hepatic encephalopathy. breath test in IBS patients as compared with healthy subjects and resolution of some IBS symptoms, especially bloating bloating Vox populi A lay term for post-prandial abdominal fullness or swelling and distention, with eradication of intestinal bacteria. The type of gas produced by gut bacteria may be an important factor in IBS symptom production. Pimantel et al (32) show that isolated methane excretion was found in constipation-predominant IBS. Methane as a gas slows intestinal transit (33) and reduces postprandial postprandial /post·pran·di·al/ (-pran´de-al) occurring after a meal. post·pran·di·al adj. Following a meal, especially dinner. plasma levels of serotonin. (34) The question remains if the observed bacterial overgrowth is a cause of disease or just a consequence of altered bowel motility, but the association for part of the IBS population is certain. Food Allergy Many IBS patients experience symptoms after a meal, (35) so the hypothesis that food intolerance is involved in the symptomatology symptomatology /symp·to·ma·tol·o·gy/ (simp?to-mah-tol´ah-je) 1. the branch of medicine dealing with symptoms. 2. the combined symptoms of a disease. symp·to·ma·tol·o·gy n. of IBS has been intensely investigated. The increased symptomatology after eating may be explained by the physiologic increase in the motor activity of the colon (36) or by the hypersensitivity state of IBS patients. Different studies of exclusion diets showed significant improvement of symptoms associated with the exclusion of different foods, mostly involving milk, eggs, and wheat. (37-43) Administration of enteral enteral /en·ter·al/ (en´ter'l) enteric. en·ter·al adj. 1. Within or by way of the intestine, as distinguished from parenteral. 2. Enteric. fats was proven to exacerbate symptoms, especially bloating. (44) The role of fiber is controversial, despite the belief that IBS is due to fiber deficiency. (45) Even if fiber supplementation improves the constipation, the increase in cereal fiber consumption is associated with worsening symptomatology. (39,46) Newer studies look at the association of IgG or IgE antibody against different foods and the improvement of symptoms when the foods are eliminated from the diet. (42,47) The foods which patients were most likely to have antibodies against included yeast, milk, egg, wheat, cashew cashew (kăsh`  , kəsh`), tropical American tree (Anacardium occidentale nuts, peas, almonds,
and barley. (47)
Infection and Inflammation The association of IBS symptoms and a recent infectious enteritis enteritis (ĕn'tərī`tĭs), inflammation of the gastrointestinal tract. Acute enteritis is not usually serious except in infants and older people, in whom the accompanying diarrhea can cause dehydration through the loss of fluids. was first noticed and described more than 75 years ago. (14,48) A few epidemic episodes of gastroenteritis gastroenteritis: see enteritis. gastroenteritis Acute infectious syndrome of the stomach lining and intestines. Symptoms include diarrhea, vomiting, and abdominal cramps. with different organisms (Entamoeba entamoeba Any protozoan of the genus Entamoeba. Most are parasites in the intestines of vertebrates, including humans. E. histolytica causes human amebic dysentery. Infection of the large intestine with E. , (49) Salmonella, (50,51) Campylobacter Campylobacter Genus of gram-negative spiral-shaped bacteria infecting mammals. Many species, especially C. fetus, cause miscarriage in sheep and cattle. C. jejuni is a common cause of food poisoning. Sources include meats (particularly chicken) and unpasteurized milk. (52,51)) were followed by a high incidence of IBS in the affected population. The risk of developing postinfectious IBS is associated with an increased duration of the episode, pathogenicity of the infectious agent, but also genetic factors. The individual's genetically determined immune response is an important factor in determining the risk to develop IBS. Gene polymorphism associated with overproduction o·ver·pro·duce tr.v. o·ver·pro·duced, o·ver·pro·duc·ing, o·ver·pro·duc·es To produce in excess of need or demand. o of TNF-alpha was significantly more prevalent in IBS as compared with controls. (53) A recent study of full thickness biopsy specimens from patients with IBS (54) found that 9 of 10 presented with signs of chronic inflammation, while others had signs of neuronal degeneration. The hypothesis is that an infection can cause IBS symptoms by several mechanisms, including injuries to the enteric nervous system The enteric nervous system (ENS) is the part of the nervous system that directly controls the gastrointestinal system. It is capable of autonomous functions such as the coordination of reflexes, although it receives considerable innervation from the autonomic nervous system which may alter the function of enteroendocrine cells and T lymphocytes and induce a chronic state of inflammation and visceral sensitivity. (54-58) Serotonin Serotonin is a neurotransmitter vital to normal GI motility, visceral sensitivity, GI immune function and blood flow. Studies at the molecular level have shown abnormalities in the serotonin reuptake reuptake /re·up·take/ (re-up´tak) reabsorption of a previously secreted substance. re·up·take n. transport system in patients with IBS. (59,60) A recent study reports that the polymorphism of 5-HT2A receptor gene may be associated with the development of IBS. (61) Altered Visceral Sensitivity Using intraluminal balloon distention, patients with IBS were proven to be more sensitive than control healthy subjects. (62) Lowered rectal pain threshold is considered a hallmark of IBS patients. (63-65) A study of the prevalence of rectal hypersensitivity showed that 64% of IBS patients were hypersensitive hy·per·sen·si·tive adj. Responding excessively to the stimulus of a foreign agent, such as an allergen; abnormally sensitive. hy . Eighty-nine percent of patients with alternating IBS were hypersensitive, while only 68% and 26% of patients with diarrhea-predominant IBS and constipation-predominant IBS, respectively, presented hypersensitivity. (66) Brain-gut Axis Changes in central nervous system perception, such as dysfunctional brain-gut axis, are currently considered the foundation of understanding IBS. Both PET and fMRI studies showed differences in the intensity of brain activation in regions like the anterior cingulate cortex The Anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex, which resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain. (ACC See adaptive cruise control. ), prefrontal cortex, insula INSULA, Latin. An island. In the Roman law the word is applied to a house not connected with other houses, but separated by a surrounding space of ground. Calvini Lex; Vicat, Vocab. ad voc. and thalamus thalamus (thăl`əməs), mass of nerve cells centrally located in the brain just below the cerebrum and resembling a large egg in size and shape. . Data suggests heightened pain sensitivity of the brain-gut axis in IBS, with either a normal (67) or abnormal (68) pattern of activation. Due to neuroplasticity from the effects of IBS, patients interpret differently the information that comes from the GI tract. New fMRI data suggests that the altered sensory processing in IBS may not be restricted to visceral sensation (69) and that looking only at the gut may mean neglecting the rest of the picture. Therefore, the approach to an IBS patient should be multisystemic mul·ti·sys·tem·ic adj. Relating to a disease or condition that affects many organ systems of the body. multisystemic affecting more than one body system. , targeting both the gut and the brain. Diagnosing IBS IBS is a diagnosis made by identification of clinical symptoms consistent with the disorder--Manning and Rome criteria should be used to raise the clinical suspicion. IBS is a functional disorder, so signs or symptoms that suggest an organic cause (Table 4) should put IBS lower on a differential diagnosis list and should require attempts to rule out other organic causes of symptoms. IBS is a chronic disorder, with symptom fluctuation, and despite a large number of therapeutic alternatives, 75% of patients are still symptomatic after 5 years. (12) Once IBS is diagnosed based on the clinical picture and minimal initial investigations to exclude other diseases are performed, the essential factors to successful management of the patient are a good doctor-patient relationship, patient education and reassurance. In the evaluation of a patient with IBS, searching for psychosocial factors, stress, and history of physical or sexual abuse may identify areas that require special attention. These issues need to be addressed to have a complete and effective management plan for the patient. When addressing a history of abuse, a decision has to be made if the issue should be addressed at the first visit, or after the doctor-patient relationship has been formed. Positive abuse history requires referral to a doctor with appropriate expertise while continuing to care for the patient's gastroenterological problems. Six studies have addressed the probability of organic disease in patients with IBS symptoms. (30,70-74) The diagnosis of IBS was made using symptom-based criteria, either Manning, Rome or modified Rome criteria. Organic disease was identified using flexible sigmoidoscopy, colonoscopy or barium enema in 0 to 1.3% of patients. (70-73) Abdominal ultrasound (73) and rectal biopsy (72) failed to identify organic diseases. Complete blood cell count blood cell count, n an estimation of the number and types of circulating blood cells (e.g., red blood cells [erythrocytic series], white blood cells, differential). , chemistry, and fecal occult blood test Fecal Occult Blood Test Definition The fecal occult blood test (FOBT) is performed as part of the routine physical examination during the examination of the rectum. identified an organic cause in 0 to 1.3% of patients, (71,74) positive stool test for ova ova (o´vah) plural of ovum. Ova Eggs. Mentioned in: Stool O & P Test ova plural of ovum. and parasites were found in 0 to 1.6%. (70,71) Abnormal TSH TSH thyroid-stimulating hormone; see thyrotropin. TSH abbr. thyroid-stimulating hormone Thyroid-stimulating hormone (TSH) was found in 0.6 to 6% of patients, and abnormal breath test for lactose intolerance was found in 22 to 26%. (70,71) One study found prevalence of celiac sprue in the IBS group to be 5%, while in the general population, it is <1%, (74) so routine evaluation for celiac sprue may be considered. One study evaluating bacterial overgrowth through breath tests found that 78% of patients had bacterial overgrowth, but the study examined only a select population of patients referred to rule out bacterial overgrowth. (30) Overall, available data does not support the performance of diagnostic tests in IBS, unless there is a need for the reassurance value of a negative evaluation for organic diseases. Based on the previous studies, once IBS is diagnosed based on clinical symptoms, we recommend minimal investigations (hematology and chemistry, erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Definition The erythrocyte sedimentation rate (ESR), or sedimentation rate (sed rate), is a measure of the settling of red blood cells in a tube of blood during one hour. , stool examination for occult blood), patient reassurance and starting symptomatic treatment. Treatments depend on the predominant symptoms of diarrhea or constipation with the use of laxatives/antidiarrheal drugs and fiber. If there is no significant improvement or there is a change in symptomatology suggestive for organic disease, then more tests may be required. There are disorders that may mimic IBS and must be excluded if the initial treatment fails (Table 5). If the IBS patient cannot be successfully managed with symptomatic treatment such as fiber, laxatives Laxatives Definition Laxatives are products that promote bowel movements. Purpose Laxatives are used to treat constipation—the passage of small amounts of hard, dry stools, usually fewer than three times a week. or antidiarrheal antidiarrheal /an·ti·di·ar·rhe·al/ (-di?ah-re´al) counteracting diarrhea, or an agent that does this. an·ti·di·ar·rhe·al n. A substance used to prevent or treat diarrhea. and antispasmodic drugs, the patient should be referred to a gastroenterologist so that further testing can be considered and therapies such as visceral analgesics Analgesics Definition Analgesics are medicines that relieve pain. Purpose Analgesics are those drugs that mainly provide pain relief. (tricyclics and serotonin modulators) can be considered. Treatment Options: Conventional Pharmacological Treatment Bulking Agents Bulking agents include various types of fiber, such as psyllium psyllium /psyl·li·um/ (sil´e-um) 1. a plant of the genus Plantago. 2. the husk (psyllium husk) or seed (plantago or psyllium seed) of various species of Plantago , methylcellulose methylcellulose /meth·yl·cel·lu·lose/ (-sel´ul-os) a methyl ester of cellulose; used as a bulk laxative and as a suspending agent for drugs and applied topically to the conjunctiva to protect and lubricate the cornea during certain , corn fiber, calcium polycarbophil, and ispaghula husk. Fiber provides bulk to the stool and is prescribed to increase stool frequency and improve stool passage. Thirteen randomized control trials (RCTs) have evaluated the effectiveness of bulking agents. (75-87) One meta-analysis suggests that soluble types of fiber may be effective at improving global IBS symptoms. Overall, bulking agents appear to be similar to placebo. Several potential side effects should be remembered--the metabolism of bulking agents by gut bacteria produces bowel gas, which may increase bloating and exacerbate the abdominal discomfort. Different bulking agents have been associated with anaphylactic anaphylactic /ana·phy·lac·tic/ (an?ah-fi-lak´tik) pertaining to anaphylaxis. anaphylactic (an´ reactions, esophageal obstruction and bowel obstruction if large quantities are used without sufficient water. Osmotic osmotic, adj pertaining to osmosis. osmotic pressure, n See pressure, osmotic. osmotic emanating from or pertaining to the pressure of osmosis. Laxatives Patients with constipation-predominant IBS have delayed intestinal transit, so osmotic laxatives may be useful in improving the stool frequency and consistency. Currently, there are no RCTs looking at the efficacy of osmotic laxatives (lactulose, PEG-3350, magnesium hydroxide, and milk of magnesia milk of magnesia, common name for the chemical compound magnesium hydroxide, Mg(OH)2. The viscous, white, mildly alkaline mixture that is used medicinally as an antacid and laxative is a suspension of approximately 8% magnesium hydroxide in water. ) in IBS patients. Antidiarrheal Agents Patients with diarrhea-predominant IBS have accelerated transit and may benefit from antidiarrheal agents. Three RCTs have evaluated the effectiveness of loperamide loperamide /lo·per·amide/ (lo-per´ah-mid) an antiperistaltic used as the hydrochloride salt as an antidiarrheal and to reduce the volume of discharge from ileostomies. for treating IBS. (88-90) The results showed that loperamide decreased stool frequency and consistency, but not abdominal discomfort or global IBS symptoms when compared with placebo. Antispasmodic Agents Antispasmodic agents decrease the intestinal smooth muscle activity, which might decrease abdominal discomfort if the pain is secondary to spasm of the intestinal smooth muscle. There are two types of smooth muscle relaxants: direct type (mebeverine, pinaverine--not available in the US), and anticholinergic/antimuscarinic agents (dicyclomine, hyoscyamine hyoscyamine /hyo·scy·amine/ (hi?o-si´ah-men) an anticholinergic alkaloid that is the levorotatory component of racemic atropine and has similar actions but twice the potency; used as an antispasmodic in gastrointestinal and urinary tract ). Three RCTs have examined the efficacy of anticholinergics available in the US. (85,91,92) The first two studies found no significant difference in the outcome of patients when compared against placebo, (85,91) while one study demonstrated significant improvement in global IBS symptoms with dicyclomine hydrochloride 40 mg four times daily. (92) Due to the high dose used in the study, 15% of the treated subjects withdrew from the study. The high dose of anticholinergics is associated with atropine-like side effects and may exacerbate the underlying constipation. Based on the current data, the antispasmodics available in the US have similar benefits as the placebo but should still be considered in the management of IBS, particularly with diarrheal symptoms. Antidepressants Antidepressants Medications prescribed to relieve major depression. Classes of antidepressants include selective serotonin reuptake inhibitors (fluoxetine/Prozac, sertraline/Zoloft), tricyclics (amitriptyline/ Elavil), MAOIs (phenelzine/Nardil), and heterocyclics Patients with IBS have visceral hypersensitivity. Tricyclic antidepressants (TCAs) in low doses are effective for chronic pain conditions, including migraine headache, neuropathic pain, noncardiac chest pain, functional dyspepsia dyspepsia: see indigestion. and IBS. The mechanism is unknown; it may be due to either reduction of sensitivity in peripheral nerves or alterations in the brain. Eight RCTs (93-100) and one meta-analysis (101) have evaluated the efficacy of tricyclic antidepressants in IBS. The data demonstrated significant improvement of abdominal discomfort in patients treated with antidepressants, as compared against placebo treatment. The odds ratio for improvement with antidepressant antidepressant, any of a wide range of drugs used to treat psychic depression. They are given to elevate mood, counter suicidal thoughts, and increase the effectiveness of psychotherapy. therapy was 4.2, with a 95% confidence interval of 2.3 to 7.9. When effectiveness of TCAs were compared in patients with diarrhea-predominant IBS versus constipation-predominant IBS, TCAs improved global IBS symptoms among the diarrhea-predominant patients, but not in the constipation-predominant group. The anticholinergic anticholinergic /an·ti·cho·lin·er·gic/ (-ko?lin-er´jik) parasympatholytic; blocking the passage of impulses through the parasympathetic nerves; also, an agent that so acts. an·ti·cho·lin·er·gic n. side effects profile (dry mouth, dizziness and constipation) makes TCAs more suitable for diarrhea-predominant IBS. Newer Pharmacological Treatments Diarrhea-predominant IBS: 5-H[T.sub.3] Antagonists-Alosetron Alosetron is a 5-H[T.sub.3] receptor antagonist that decreases small intestine and colonic transit and mediates colonic afferent nerve activity, making it a drug for diarrhea-predominant IBS. Four RCTs (102-105) have evaluated the effectiveness of alosetron in IBS management. All trials demonstrated significant improvement in global IBS symptoms, stool frequency, consistency and abdominal discomfort among women with diarrhea-predominant IBS. Alosetron use is limited by the side effect profile (ischemic colitis and constipation). The FDA FDA abbr. Food and Drug Administration FDA, n.pr See Food and Drug Administration. FDA, n.pr the abbreviation for the Food and Drug Administration. approved alosetron only for severe, diarrhea-predominant IBS in women who have failed conventional therapies. Constipation-predominant IBS: 5-H[T.sub.4] Agonists-Tegaserod The 5-H[T.sub.4] receptor agonist, tegaserod, stimulates the peristaltic peristaltic pertaining to or emanating from peristalsis. peristaltic reflex onward movement of a bolus of ingesta in the intestine is preceded by a reflex dilation of the intestine. reflex, increases small intestine and colonic transit and mediates visceral hypersensitivity by reducing the activity of colonic afferent nerves. (106) Tegaserod is approved by the FDA for treating constipation-predominant IBS in women. Six RCTs have evaluated the effectiveness of tegaserod. (107-112) All six trials demonstrated that tegaserod is more effective than placebo, with improvement of global IBS symptoms, bloating, abdominal discomfort and altered bowel habits in constipation-predominant IBS. The most common side effects of tegaserod are diarrhea and headaches. Newer agents are currently being explored in phase II trials: cholecystokinin cholecystokinin /cho·le·cys·to·ki·nin/ (CCK) (-ki´nin) a polypeptide hormone secreted in the small intestine that stimulates gallbladder contraction and secretion of pancreatic enzymes. antagonists, (113) [alpha]2 adrenergic agonists (clonidine clonidine /clo·ni·dine/ (klo´ni-den) a centrally acting antihypertensive agent, used as the hydrochloride salt; also used in the prophylaxis of migraine and the treatment of dysmenorrhea, menopausal symptoms, opioid withdrawal, and ), (114) k-opioid agonists (fedotozine), (115-117) a SSRI SSRI selective serotonin reuptake inhibitor. SSRI n. Selective serotonin reuptake inhibitor; a class of drugs that inhibit the reuptake of serotonin in the central nervous system, used to treat depression and other (citalopram citalopram /ci·tal·o·pram/ (si-tal´o-pram) 1. an antidepressant compound used in the treatment of major depressive disorder, administered orally as the hydrobromide. 2. ), (118) and neurokinin antagonists. (119-122) Alternative Therapies Acupuncture -- Despite early studies that showed the effectiveness of acupuncture in IBS, (123,124) newer, placebo-controlled studies show a placebo type effect--both acupuncture and placebo cause improvements, with no difference between the two groups. (125,126) Hypnotherapy Hypnotherapy Definition Hypnotherapy is the treatment of a variety of health conditions by hypnotism or by inducing prolonged sleep. Pioneers in this field, such as James Braid and James Esdaile discovered that hypnosis could be used to -- Hypnotherapy has been shown in RCTs to have a small but significant improvement in abdominal pain, abdominal distention and general well being, with long-lasting benefits. (127,128) Chinese herbal medicine Chinese herbal medicine see herbal medicine. -- A placebo-controlled trial reported that Chinese herbal medicine significantly improved bowel symptom scores and global symptom improvement, with reported benefits beyond the actual treatment period. (129) References 1. Longstreth GF, Thompson WG, Chevy WD, et al. Functional bowel disorders. Gastroenterology 2006;130:1480-1491. 2. Manning AP, Thompson WG, Heaton KW, et al. Towards positive diagnosis of the irritable bowel. Br Med J 1978;2:653-654. 3. Kruis W, Thieme C, Weinzierl M, et al. A diagnostic score for the irritable bowel syndrome: its value in the exclusion of organic disease. Gastroenterology 1984;87:1-7. 4. Talley NJ, Zinsmeister AR, Van Dyke C, et al. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991;101:927-934. 5. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders: prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38:1569-1580. 6. Saito YA, Locke GR, Talley NJ, et al. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol 2000;95:2816-2824. 7. Schuster MM. Defining and diagnosing irritable bowel syndrome. Am J Manag Care 2001;7 (Suppl 8):S246-S251. 8. National Ambulatory Medical Care Survey. National Center for Health Statistics National Center for Health Statistics (NCHS) is part of the Centers for Disease Control and Prevention (CDC), which is part of the United States Department of Health and Human Services. NCHS is the United States' principal health statistics agency. . Available at: http://www.cdc.gov/nchs/about/major/ahcd/namcsdes.htm. Accessed April 2006. 9. Mitchell CM, Drossman DA. Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology 1987;92:1282-1284. 10. Talley NJ, Gabriel SE, Harmsen WS, et al. Medical costs in community subjects with irritable bowel syndrome. Gastroenterology 1995;109:1736-1741. 11. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002;122:1500-1511. 12. Harvey RF, Mauad EC, Brown AM. Prognosis in the irritable bowel syndrome: a 5-year prospective study. Lancet 1987;1:963-965. 13. Cumming W. Electro-galvanism in a peculiar affection of the mucous membrane of the bowels. London Medical Gazette 1849:969-973. 14. Ryle JA. Chronic spasmodic spasmodic /spas·mod·ic/ (spaz-mod´ik) of the nature of a spasm; occurring in spasms. spas·mod·ic adj. 1. Relating to, affected by, or having the character of a spasm; convulsive. affections of the colon. Lancet 1928;2:1115-1119. 15. Hollander E. Mucous colitis due to food allergy with a report of five cases. Am J Med Sci 1927;174:495-500. 16. Bockus HL, Bank J, Wilkinson SA. Neurogenic neurogenic /neu·ro·gen·ic/ (-jen´ik) 1. forming nervous tissue. 2. originating in the nervous system or from a lesion in the nervous system. mucous colitis. Am J Med Sci 1928;176:813-823. 17. Kellow JE, Phillips SF. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987;92:1885-1893. 18. Kellow JE, Phillips SF, Miller LJ, et al. Dysmotility of the small intestine in irritable bowel syndrome. Gut 1988;29:1236-1243. 19. Chey WY, Jin HO, Lee MH, et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001;96:1499-1506. 20. Mathias JR, Clench MH. Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract. Dig Dis 1998;16:3-13. 21. Mathias JR, Clench MH, Abell TL, et al. Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal pre·me·no·paus·al adj. Of or relating to the years or the stage of life immediately before the onset of menopause. premenopausal adjective women with functional bowel disease: a double-blind, placebo-controlled, randomized study. Dig Dis Sci 1998;43:1347-1355. 22. Mathias JR, Ferguson KL, Clench MH. Debilitating de·bil·i·tat·ing adj. Causing a loss of strength or energy. Debilitating Weakening, or reducing the strength of. Mentioned in: Stress Reduction 'functional' bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog. Dig Dis Sci 1989;34:761-766. 23. Ruigomez A, Garcia Rodriguez LA, Johansson S, et al. Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Maturitas 2003;44:133-140. 24. Heitkemper MM, Cain KC, Jarrett ME, et al. Symptoms across the menstrual cycle in women with irritable bowel syndrome. Am J Gastroenterol 2003;98:420-430. 25. Morris-Yates A, Talley NJ, Boyce PM, et al. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol 1998;93:1311-1317. 26. Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 2001;121:799-804. 27. Levy RL, Whitehead WE, Von Korff MR, et al. Intergenerational transmission of gastrointestinal illness behavior. Am J Gastroenterol 2000;95:451-456. 28. Drossman DA, Leserman J, Nachman G, et al. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med 1990;113:828-833. 29. Drossman DA, Talley NJ, Leserman J, et al. Sexual and physical abuse and gastrointestinal illness: review and recommendations. Ann Intern Med 1995;123:782-794. 30. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth intestinal bacterial overgrowth Afferent loop syndrome, gastrojejunal loop obstruction, stagnant loop syndrome Infectious disease A condition characterized by excess growth of opportunistic bacteria, which occurs when normal gut flora is eradicated with antibiotics reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000;95:3503-3506. 31. Pimentel M, Chow EJ, Lin HC. Normalization In relational database management, a process that breaks down data into record groups for efficient processing. There are six stages. By the third stage (third normal form), data are identified only by the key field in their record. of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2003;98:412-419. 32. Pimentel M, Mayer AG, Park S, et al. Methane production during lactulose breath test is associated with gastrointestinal disease presentation. Dig Dis Sci 2003;48:86-92. 33. Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile contractile /con·trac·tile/ (kon-trak´til) able to contract in response to a suitable stimulus. con·trac·tile adj. Capable of contracting or causing contraction, as a tissue. activity. Am J Physiol Gastrointest Liver Physiol 2006;290:G1089-G1095. 34. Pimentel M, Kong Y, Park S. IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen. Dig Dis Sci 2004;49:84-87. 35. Ragnarsson G, Bodemar G. Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS): patients' description of diarrhea, constipation and symptom variation during a prospective 6-week study. Eur J Gastroenterol Hepatol 1998;10:415-421. 36. Rogers J, Raimundo AH, Misiewicz JJ. Cephalic phase of colonic pressure response to food. Gut 1993;34:537-543. 37. Bentley SJ, Pearson DJ, Rix KJ. Food hypersensitivity in irritable bowel syndrome. Lancet 1983;2:295-297. 38. Farah DA, Calder I, Benson L, et al. Specific food intolerance: its place as a cause of gastrointestinal symptoms. Gut 1985;26:164-168. 39. Jones VA, McLaughlan P, Shorthouse M, et al. Food intolerance: a major factor in the pathogenesis of irritable bowel syndrome. Lancet 1982;2:1115-1117. 40. McKee AM, Prior A, Whorwell PJ. Exclusion diets in irritable bowel syndrome: are they worthwhile? J Clin Gastroenterol 1987;9:526-528. 41. Nanda R, James R, Smith H, et al. Food intolerance and the irritable bowel syndrome. Gut 1989;30:1099-1104. 42. Petitpierre M, Gumowski P, Girard JP. Irritable bowel syndrome and hypersensitivity to food. Ann Allergy 1985;54:538-540. 43. Zwetchkenbaum J, Burakoff R. The irritable bowel syndrome and food hypersensitivity. Ann Allergy 1988;61:47-49. 44. Serra J, Salvioli B, Azpiroz F, et al. Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology 2002;123:700-706. 45. Bijkerk CJ, de Wit NJ, Stalman WA, et al. Irritable bowel syndrome in primary care: the patients' and doctors' views on symptoms, etiology and management. Can J Gastroenterol 2003;17:363-368; quiz 405-366. 46. Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet 1994;344:39-40. 47. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised Adj. 1. randomised - set up or distributed in a deliberately random way randomized irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" controlled trial. Gut 2004;53:1459-1464. 48. Chaudhary NA, Truelove SC. The irritable colon syndrome: a study of the clinical features, predisposing causes, and prognosis in 130 cases. Q J Med 1962;123:307-322. 49. Stewart GT. Post-dysenteric colitis. Br Med J 1950;1:405-409. 50. McKendrick MW, Read NW. Irritable bowel syndrome: post salmonella infection. J Infect 1994;29:1-3. 51. Rodriguez LA, Ruigomez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study. BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift 1999;318:565-566. 52. Thornley JP, Jenkins D, Neal K, et al. Relationship of Campylobacter toxigenicity toxigenicity /tox·i·ge·nic·i·ty/ (tok?si-je-nis´i-te) the property of producing toxins. toxigenicity the capacity to produce toxins. in vitro to the development of postinfectious irritable bowel syndrome. J Infect Dis 2001;184:606-609. 53. van der Veek PP, van den Berg Van den Berg is the surname of:
n. pl. kroon·i See Table at currency. [Estonian, from German Krone, from Middle High German kr YE, et al. Role of tumor necrosis factor-alpha Tumor necrosis factor (TNF, cachexin or cachectin and formally known as tumor necrosis factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol 2005;100:2510-2516. 54. Tornblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of the jejunum jejunum: see intestine. reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002;123:1972-1979. 55. Gwee KA. Postinfectious irritable bowel syndrome. Curr Treat Options Gastroenterol 2001;4:287-291. 56. Gwee KA, Graham JC, McKendrick MW, et al. Psychometric psy·cho·met·rics n. (used with a sing. verb) The branch of psychology that deals with the design, administration, and interpretation of quantitative tests for the measurement of psychological variables such as intelligence, aptitude, and scores and persistence of irritable bowel after infectious diarrhoea. Lancet 1996;347:150-153. 57. Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut 1999;44:400-406. 58. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000;47:804-811. 59. Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics Pharmacogenetics Definition Pharmacogenetics is the study of how the actions of and reactions to drugs vary with the patient's genes. Description in diarrhea-predominant irritable bowel syndrome. Gastroenterology 2002;123:425-432. 60. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 2004;126:1657-1664. 61. Pata C, Erdal E, Yazc K, et al. Association of the -1438 G/A G/A Gate/Array (NEC) G/A Ground/Air G/A Ground-to-Air and 102 T/C T/C Table of Contents T/C To Consider T/C Take Care T/C Thermocouple T/C Telephone Call T/C Teleconference T/C Transfer Case T/C Time Charter T/C Torque Converter T/C Textile and Clothing (industry sector) T/C Terry Cloth polymorphism of the 5-Ht2A receptor gene with irritable bowel syndrome 5-Ht2A gene polymorphism in irritable bowel syndrome. J Clin Gastroenterol 2004;38:561-566. 62. Mertz H, Naliboff B, Munakata J, et al. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 1995;109:40-52. 63. Bouin M, Plourde V, Boivin M, et al. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology 2002;122:1771-1777. 64. Ritchie J. Pain from distension dis·ten·tion also dis·ten·sion n. The act of distending or the state of being distended. [Middle English distensioun, from Old French, from Latin of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 1973;14:125-132. 65. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology 1990;98:1187-1192. 66. Rey E, Diaz-Rubio M. Prevalence of rectal hypersensitivity in patients with irritable bowel syndrome and its clinical subgroups. Rev Esp Enferm Dig 2002;94:247-258. 67. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and non-painful rectal distention. Gastroenterology 2000;118:842-848. 68. Silverman DH, Munakata JA, Ennes H, et al. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997;112:64-72. 69. Andresen V, Bach DR, Poellinger A, et al. Brain activation responses to subliminal subliminal /sub·lim·i·nal/ (-lim´i-n'l) below the threshold of sensation or conscious awareness. sub·lim·i·nal adj. 1. Below the threshold of conscious perception. Used of stimuli. or supraliminal supraliminal /su·pra·lim·i·nal/ (-lim´i-n'l) above the threshold of sensation. su·pra·lim·i·nal adj. Being above the threshold of consciousness or of sensation. Used of stimuli. rectal stimuli and to auditory stimuli in irritable bowel syndrome. Neurogastroenterol Motil 2005:17:827-837. 70. Hamm LR, Sorrells SC, Harding JP, et al. Additional investigations fail to alter the diagnosis of irritable bowel syndrome in subjects fulfilling the Rome criteria. Am J Gastroenterol 1999;94:1279-1282. 71. Tolliver BA, Herrera JL, DiPalma JA. Evaluation of patients who meet clinical criteria for irritable bowel syndrome. Am J Gastroenterol 1994;89:176-178. 72. Macintosh DG, Thompson WG, Patel DG, et al. Is rectal biopsy necessary in irritable bowel syndrome? Am J Gastroenterol 1992;87:1407-1409. 73. Francis CY, Duffy JN, Whorwell PJ, et al. Does routine abdominal ultrasound enhance diagnostic accuracy in irritable bowel syndrome? Am J Gastroenterol 1996;91:1348-1350. 74. Sanders DS, Carter MJ, Hurlstone DP, et al. Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. Lancet 2001;358:1504-1508. 75. Manning AP, Heaton KW, Harvey RF. Wheat fibre and irritable bowel syndrome: a controlled trial. Lancet 1977;2:417-418. 76. Arthurs Y, Fielding JF. Double blind trial of ispaghula/poloxamer in the irritable bowel syndrome. Ir Med J 1983;76:253. 77. Arffmann S, Andersen JR, Hegnhoj J, et al. The effect of coarse wheat bran in the irritable bowel syndrome: a double-blind cross-over study. Scand J Gastroenterol 1985;20:295-298. 78. Longstreth GF, Fox DD, Youkeles L, et al. Psyllium therapy in the irritable bowel syndrome: a double-blind trial. Ann Intern Med 1981;95:53-56. 79. Prior A, Whorwell PJ. Double blind study of ispaghula in irritable bowel syndrome. Gut 1987;28:1510-1513. 80. Lucey MR, Clark ML, Lowndes J, et al. Is bran efficacious in irritable bowel syndrome? A double blind placebo controlled crossover study. Gut 1987;28:221-225. 81. Cook IJ, Irvine EJ, Campbell D, et al. Effect of dietary fiber on symptoms and rectosigmoid motility in patients with irritable bowel syndrome: a controlled, crossover study. Gastroenterology 1990;98:66-72. 82. Toskes PP, Connery KL, Ritchey TW. Calcium polycarbophil compared with placebo in irritable bowel syndrome. Aliment al·i·ment n. 1. Something that nourishes; food. 2. Something that supports or sustains. v. To supply with sustenance, such as food. aliment food; nutritive material. Pharmacol Ther 1993;7:87-92. 83. Snook snook: see bass, fish. snook Any of about eight species (genus Centropomus) of tropical marine fishes that are long and silvery and have two dorsal fins, a long head, and a large mouth with a projecting lower jaw. J, Shepherd HA. Bran supplementation in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 1994;8:511-514. 84. Soltoft J, Krag B, Gudmand-Hoyer E, et al. A double-blind trial of the effect of wheat bran on symptoms of irritable bowel syndrome. Lancet 1976;1:270-272. 85. Ritchie JA, Truelove SC. Treatment of irritable bowel syndrome with lorazepam lorazepam /lor·a·ze·pam/ (lor-az´e-pam) a benzodiazepine used as an antianxiety agent, sedative-hypnotic, preanesthetic medication, and anticonvulsant. lor·az·e·pam n. , hyoscine hyoscine (hī`ōsēn, –sĭn): see scopolamine. butylbromide, and ispaghula husk. Br Med J1979;1:376-378. 86. Jalihal A, Kurian G. Ispaghula therapy in irritable bowel syndrome: improvement in overall well-being is related to reduction in bowel dissatisfaction. J Gastroenterol Hepatol 1990;5:507-513. 87. Golechha AC, Chadda VS, Chadda S, et al. Role of ispaghula husk in the management of irritable bowel syndrome (a randomized double-blind crossover study). J Assoc Physicians India 1982;30:353-355. 88. Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol Suppl 1987;130:81-84. 89. Efskind PS, Bernklev T, Vain MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996;31:463-468. 90. Cann PA, Read NW, Holdsworth CD, et al. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984;29:239-247. 91. Wheatley D. Irritable colon syndrome treated with an antispasmodic antispasmodic /an·ti·spas·mod·ic/ (-spaz-mod´ik) 1. preventing or relieving spasms. 2. an agent that so acts. an·ti·spas·mod·ic adj. drug. Practitioner 1976;217:276-280. 92. Page JG, Dirnberger GM. Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol 1981: 3:153-156. 93. Heefner JD, Wilder RM, Wilson ID. Irritable colon and depression. Psychosomatics 1978;19:540-547. 94. Steinhart MJ, Wong PY, Zarr ML. Therapeutic usefulness of amitriptyline amitriptyline /am·i·trip·ty·line/ (am?i-trip´ti-len) a tricyclic antidepressant with sedative effects; also used in treating enuresis, chronic pain, peptic ulcer, and bulimia nervosa. in spastic colon syndrome, bit J Psychiatry Med 1981:11:45-57. 95. Myren J, Groth H, Larssen SE, et al. The effect of trimipramine in patients with the irritable bowel syndrome: a double-blind study. Scand J Gastroenterol 1982;17:871-875. 96. Myren J, Lovland B, Larssen SE, et al. A double-blind study of the effect of trimipramine in patients with the irritable bowel syndrome. Scand J Gastroenterol 1984;19:835-843. 97. Greenbaum DS, Mayle JE, Vanegeren LE, et al. Effects of desipramine desipramine /de·sip·ra·mine/ (des-ip´rah-men) a tricyclic antidepressant of the dibenzazepine class; used as the hydrochloride salt. desipramine a tricyclic antidepressant. on irritable bowel syndrome compared with atropine atropine (ăt`rəpēn, –pĭn), alkaloid drug derived from belladonna and other plants of the family Solanaceae (nightshade family). and placebo. Dig Dis Sci 1987:32:257-266. 98. Vij JG, Jiloha RG, Kumar N. Effect of antidepressant drug (doxepin) on irritable bowel syndrome patients. Indian J Psychiatry 1991:243-246. 99. Rajagopalan M, Kurian G, John J. Symptom relief with amitriptyline in the irritable bowel syndrome. J Gastroenterol Hepatol 1998;13:738-741. 100. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 2003;125:19-31. 101. Jackson JL, O'Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med 2000;108:65-72. 102. Lembo T, Wright RA, Bagby B, et al. Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2001:96:2662-2670. 103. Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Titer 1999;13:1149-1159. 104. Camilleri M, Northcutt AR, Kong S. et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000;355:1035-1040. 105. Jones RH, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female non-constipated irritable bowel syndrome patients. Aliment Pharmacol Titer 1999;13:1419-1427. 106. Camilleri M. Review article: tegaserod. Aliment Pharmacol Titer 2001;15:277-289. 107. Muller-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001;15:1655-1666. 108. Whorwell PJ, Krumholz S, Muller-Lissner SA. Tegaserod has a favorable safety and tolerability profile in patients with constipation-predominant and alternating forms of irritable bowel syndrome. Gastroenterology 2000:118: A1204. 109. Schoenfeld P, Chey WD, Drossman D. Effectiveness and safety of tegaserod in the treatment of irritable bowel syndrome: a meta-analysis of randomized controlled trials. Gastroenterology 2002:112:A 1486. 110. Novick J, Miner P, Krause R, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2002;16:1877-1888. 111. Kellow J, Lee OY, Chang FY, et al. An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut 2003;52:671-676. 112. Nyhlin H, Bang C, Elsborg T. Tegaserod is an effective and safe therapy for IBS in a Nordic population. Gastroenterology 2003:124: M1645. 113. Cremonini F, Camilleri M, McKinzie S, et al. Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study. Am J Gastroenterol 2005;100:652-663. 114. Camilleri M, Kim DY, McKinzie S, et al. A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2003;1:111-121. 115. Corazziari E. Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol 1999;13(suppl A):71A-75A. 116. Dapoigny M, Abitbol JL, Fraitag B. Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome: a multicenter dose-response study. Dig Dis Sci 1995;40:2244-2249. 117. Delvaux M, Louvel D, Lagier E, et al. The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome. Gastroenterology 1999;116:38-45. 118. Masand PS, Gupta S, Schwartz TL, et al. Open-label treatment with citalopram in patients with irritable bowel syndrome: a pilot study. Prim Care Companion J Clin Psychiatry 2005;7:162-166. 119. Lecci A, Maggi CA. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin Ther Targets 2003;7:343-362. 120. Tough IR, Lewis CA, Fozard J, et al. Dual and selective antagonism of neurokinin NK(1) and NK(2) receptor-mediated responses in human colon mucosa. Naunyn Schmiedebergs Arch Pharmacol 2003;367:104-108. 121. Furness JB. TAK-637: Takeda. Curr Opin Investig Drugs 2001;2:1437-1440. 122. Evangelista S. Eziopitant: Pfizer. Curr Opin Investig Drugs 2001;2:1441-1443. 123. Xiao WB, Liu YL. Rectal hypersensitivity reduced by acupoint acupoint /acu·point/ (ak´u-point) any of the specific sites for needle insertion in acupuncture; also used in other therapies, including acupressure and moxibustion. Most are areas of high electrical conductance on the body surface. TENS in patients with diarrhea-predominant irritable bowel syndrome: a pilot study. Dig Dis Sci 2004;49:312-319. 124. Chan J, Carr I, Mayberry JF. The role of acupuncture in the treatment of irritable bowel syndrome: a pilot study. Hepatogastroenterology 1997;44:1328-1330. 125. Forbes A, Jackson S, Walter C, et al. Acupuncture for irritable bowel syndrome: a blinded placebo-controlled trial. World J Gastroenterol 2005;11:4040-4044. 126. Rohrbock RB, Hammer J, Vogelsang H, et al. Acupuncture has a placebo effect on rectal perception but not on distensibility dis·ten·si·ble adj. That can be distended: a fish with a distensible stomach. dis·ten and spatial summation: a study in health and IBS. Am J Gastroenterol 2004;99:1990-1997. 127. Whorwell PJ, Prior A, Colgan SM. Hypnotherapy in severe irritable bowel syndrome: further experience. Gut 1987;28:423-425. 128. Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. Lancet 1984;2:1232-1234. 129. Bensoussan A, Talley NJ, Hing M, et al. Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA JAMA abbr. Journal of the American Medical Association 1998;280:1585-1589. Mihaela Podovei, MD, and Braden Kuo, MD From the GI Unit, Massachusetts General Hospital Massachusetts General Hospital Health care The major teaching hospital for Harvard Medical School, widely regarded as one of the best health care centers in the world , Boston, MA. Reprint requests to Braden Kuo, GRJ GRJ George, South Africa - George (Airport Code) GRJ Gatekeeper Rejection (Cisco) 719, GI Unit, Massachusetts General Hospital, Boston, MA 02114. Email: bkuo@partners.org Dr. Kuo receives research grants from Smartpill, Forrest, Novartis, and Trine. He is a consultant for Smartpill and GlaxoSmithKline. He is also on the speaker's bureau for Novartis and receives fellowship support from Smartpill. Dr. Podovei has no disclosures to declare. Accepted April 11, 2006. RELATED ARTICLE: Key Points * Irritable bowel syndrome (IBS) is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or changes in bowel habits, with symptoms present for at least 12 weeks out of the previous 12 months. * IBS is a common disorder, more commonly present in women, that accounts for 28% of the visits to gastroenterologist. * Diagnosis is based on the clinical symptoms, keeping the investigations to a minimum. * Symptomatic treatment depends on the predominant symptom: antidiarrheal drugs in diarrhea-predominant IBS, fiber and laxatives in constipation-predominant IBS, antispasmodics for abdominal pain. * If the initial treatment fails to improve symptoms or if changes suggestive of organic disease appear, more investigations/referral may be necessary. * Newer drugs to be used are antidepressants, 5-HT3 antagonists (alosetron) for diarrhea-predominant IBS, 5-HT4 agonists (tegaserod) for constipation-predominant IBS.
Table 1. Manning criteria (1978) for the diagnosis of IBS
Manning criteria (1978)
* Abdominal pain relieved by defecation
* Looser stools with the onset of pain
* More frequent stool with the onset of pain
* Abdominal distention
* Passage of mucus in stools
* Sensation of incomplete evacuation
Table 2. Kruis criteria (1984) for the diagnosis of IBS
Kruis criteria (1984)
* Are you here because of abdominal pain?
* Do you suffer from flatulence?
* Do you suffer from irregular bowel movements?
* Have you suffered from your complaints for more than 2 years?
* How can your abdominal pain be described--burning, cutting, very
strong, terrible, feeling of pressure, dull, boring, not so bad?
* Have you noticed alternating diarrhea and constipation?
* Does your stool have any of the following properties: pencil-like,
rabbit pellets, mucus, formed and hard and then loose?
* Presence of abnormal physical exam findings or abnormal laboratory
tests (weight loss, low weight, low hemoglobin, elevated sedimentation
rate, elevated white blood cell count, fever during last week)
Table 3. Rome III criteria for the diagnosis of IBS
Rome III criteria (2006)
Recurrent abdominal pain or discomfort at least 3 days per month in the
last 3 months with symptom onset at least 6 months prior to diagnosis
associated with 2 or more of the following:
* Relieved with defecation, and/or
* Onset associated with change in frequency of stool, and/or
* Onset associated with change in form (appearance) of stool Symptoms
that cumulatively support the diagnosis of IBS:
* IBS with constipation (IBS-C)-hard or lump stools = 25% and loose
(mushy) or watery stools <25% of bowel movements
* IBS with diarrhea (IBS-D)-loose (mushy) or watery stools = 25% and
hard or lump stool <25% of bowel movements
* Mixed IBS (IBS-M)-hard or lumpy stools = 25% and loose (mushy) or
watery stools <25% of bowel movements
* Unsubtyped IBS-insufficient abnormality of stool consistency to meet
criteria for IBS C, D, or M
* IBS with constipation (IBS-C)-hard or lump stools = 25% and loose
(mushy) or watery stools <25% of bowel movements
Table 4. Red flags/alarm signs negatively associated with IBS
Alarm signs negatively associated with IBS
* Hematochezia
* Anemia
* Fever
* Weight loss more than 10 pounds
* Strong family history of colorectal cancer
Table 5. Disorders that may mimic IBS
Diarrhea-predominant Constipation-predominant
Disease Diagnostic tests Disease Diagnostic tests
Lactose, fructose Detailed dietary Pelvic floor Colonic transit,
or sorbitol history may dysfunction anorectal
intolerance identify manometry,
aggravating rectal emptying
factors, lactose studies,
hydrogen breath defecation
test, lactose proctogram
exclusion diet
Celiac disease Serologic testing,
intestinal
biopsy,
gluten-free diet
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