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T h e n e w e ng l a n d j o u r na l o f m e dic i n e This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. A 28-year-old woman presents with a 7-month history of recurrent, crampy pain in
the left lower abdominal quadrant, bloating with abdominal distention, and fre-
quent, loose stools. She reports having had similar but milder symptoms since child-
hood. She spends long times in the bathroom because she is worried about uncon-
trollable discomfort and fecal soiling if she does not completely empty her bowels
before leaving the house. She feels anxious and fatigued and is frustrated that her
previous physician did not seem to take her distress seriously. Physical examination
is unremarkable except for tenderness over the left lower quadrant. How should her
case be evaluated and treated?
Irritable bowel syndrome (IBS), characterized by chronically recurring abdominal From the Center for Neurobiology of Stress, pain or discomfort and altered bowel habits, is one of the most common syndromes seen by gastroenterologists and primary care providers, with a worldwide prevalence ments of Medicine, Physiology, and Psy-chiatry, David Geffen School of Medicine of 10 to 15%.1 In the absence of detectable organic causes, IBS is referred to as a at UCLA, Los Angeles. Address reprint functional disorder, which is defined by symptom-based diagnostic criteria known requests to Dr. Mayer at the University of as the “Rome criteria” (Table 1).2 California, Los Angeles, Peter Ueberroth Bldg., Ste. 2338 F, 10945 Leconte Ave., IBS is one of several functional gastrointestinal disorders (including functional Los Angeles, CA 90095-6949, or at dyspepsia); these other functional disorders are frequently seen in patients with IBS,3 as are other pain disorders, such as fibromyalgia, chronic pelvic pain, and inter- stitial cystitis.4,5 Coexisting psychological conditions are also common, primarily Copyright 2008 Massachusetts Medical Society. anxiety, somatization, and symptom-related fears (e.g., “I am worried that I will have severe discomfort during the day if I don’t empty my bowels completely in the morning”); these contribute to impairments in quality of life6 and excessive use Symptoms characteristic of IBS are common in population-based samples of healthy persons. However, only 25 to 50% of persons with such symptoms (typi- cally those with more frequent or severe abdominal pain) seek medical care.1 Longitudinal studies suggest substantial fluctuations in symptoms over time. In a population-based longitudinal study over a period of 12 years, 55% of subjects who initially reported symptoms of IBS did not report these symptoms at the time of the final survey.3 Although the IBS symptoms resolved in the majority of subjects, transitions to other complexes of gastrointestinal symptoms, such as functional Symptoms of IBS (or other related functional gastrointestinal symptoms) fre- quently date back to childhood; the estimated prevalence of IBS in children is similar to that in adults.8 The female-to-male ratio is 2:1 in most population-based samples and is higher among those who seek health care.4 IBS-like symptoms de- velop in approximately 10% of adult patients after bacterial or viral enteric infections; n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. Table 1. The Rome Diagnostic Criteria for Irritable Bowel Syndrome (IBS).*
Recurrent abdominal pain or discomfort at least 3 days per month for the past 3 months, associated with two or more Improvement with defecationOnset associated with a change in frequency of stoolOnset associated with a change in form (appearance) of stool * Data are from Longstreth et al.2 Criteria must have been fulfilled for the past 3 months, with symptom onset at least 6 months before diagnosis. On the basis of the predominant bowel habit, IBS has been categorized into one of the fol- lowing subgroups: IBS with diarrhea (more common in men), IBS with constipation (more common in women), and IBS with mixed bowel habits. Each group accounts for about one third of all patients. According to current diagnostic criteria, IBS must be differentiated from functional abdominal pain syndrome (in IBS, symptoms of abdominal pain are associated with alterations in bowel movements) and from chronic functional constipation and chronic functional diar- rhea (in IBS, pain and discomfort are associated with altered bowel habits).
risk factors for the development of postinfectious (Table 1) and who do not have warning signs. IBS include female sex, a longer duration of gas- These warning signs include rectal bleeding, troenteritis, and the presence of psychosocial anemia, weight loss, fever, family history of colon factors (including a major life stress at the time cancer, onset of the first symptom after 50 years of infection and somatization).9 Both initial pre- of age, and a major change in symptoms. Pa- sentations and exacerbations of IBS symptoms tients should be asked about the specifics of their are often preceded by major psychological stress- bowel habits and stool characteristics; on the ba- ors1 or by physical stressors (e.g., gastrointestinal sis of this information, they can be subclassified as having diarrhea-predominant IBS, constipation- Given the direct association between symp- predominant IBS, or mixed bowel habits.2 toms of IBS and stress, the frequent coexisting In patients who meet the Rome criteria and psychiatric conditions,10 and the responsiveness have no warning signs, the differential diagnosis of symptoms in many persons to therapies di- includes celiac sprue (Fig. 1), microscopic and rected at the central nervous system, IBS is often collagenous colitis and atypical Crohn’s disease described as a “brain–gut disorder,” although its for patients with diarrhea-predominant IBS, and pathophysiology remains uncertain. Alterations chronic constipation (without pain) for those in gastrointestinal motility and in the balance of with constipation-predominant IBS. A relation- absorption and secretion in the intestines may ship between symptoms and food intake, as well underlie irregularities in bowel habits,1 and these as possible triggers for the onset of symptoms abnormalities may be mediated in part by dys- (e.g., gastrointestinal infection or marked stress- regulation of the gut-based serotonin signaling ors) should be assessed, since this may guide system.11 Increased perception of visceral stimuli treatment recommendations. In addition, atten- may contribute to abdominal pain and discom- tion should be paid to symptoms that suggest fort.12 Preliminary reports suggest that altera- other functional gastrointestinal and somatic tions in immune activation of the mucosa1,9 and pain disorders and psychological conditions often in intestinal microflora13 may contribute to symp- associated with IBS.
toms of IBS, yet a causative role remains to be Clinical experience suggests that accepting the patient’s symptoms and distress as real, and not simply as a manifestation of excessive worrying and somatization, and providing the patient with a plausible model of the disease (e.g., “brain–gut Evaluation
disorder”) facilitates the establishment of a posi- According to current clinical guidelines,1,2,14,15 tive patient–doctor relationship. Evidence sug- IBS can generally be diagnosed without additional gests that an approach that includes acknowl- testing beyond a careful history taking, a general edging the disease, educating the patient about physical examination, and routine laboratory the disease, and reassuring the patient may im- studies (not including colonoscopy) in patients prove the treatment outcome.19 Physical exami- who have symptoms that meet the Rome criteria nation frequently reveals tenderness in the left n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e Rectal bleedingAnemiaWeight lossFeverFamily history of colon cancerOnset of first symptom after 50 yr of ageMajor change in symptoms Complete cell countBlood chemical studiesMeasurement of thyrotropin Figure 1. Differential Diagnosis.
Testing for celiac sprue may be useful in patients who meet the Rome criteria16 (especially in those with diarrhea-
predominant IBS), in patients who have warning signs, and in populations in which the prevalence of celiac sprue is high.17 If there are no warning signs, then basic blood counts, serum biochemical 3rd measurement of thyrotropin levels are indRevised icated only if there is a supportive clinical ended only in patients who have warning si SIZE
e performed in patients at the age of 50 years or older, re- gardless of whether IBS symptoms are present. If there has been a major qualitative change in the pattern of chronic AUTHOR, PLEASE NOTE:
symptoms, a new coexisting conditio Figure has been redrawn and type has been reset.
n should be suspected, and a more comprehensive diagnostic approach is Please check carefully.
lower quadrant over a palpable sigmoid colon. Pharmacologic Treatment
A rectal examination is warranted to rule out rec- Symptomatic treatment (usually aimed at normal- tal disease and abnormal function of the ano- izing bowel habits or decreasing abdominal pain) rectal sphincter (e.g., paradoxical pelvic-floor con- by a reassuring health care provider typically traction during a defecation attempt), which may provides relief for patients with mild symptoms contribute to symptoms of constipation.
who are seen in primary care settings.20 However, n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. the treatment of patients who have more severe rience indicates that these agents are generally symptoms remains challenging. Only a small effective. Regular use of low doses (e.g., 2 mg of number of pharmacologic and psychological treat- loperamide every morning or twice a day) seems ments are supported by well-designed random- to be effective for the treatment of otherwise un- ized, controlled trials involving patients with IBS. controllable diarrhea and may decrease patients’ Treatment of IBS with currently available drugs anxiety about uncontrollable urgency and fecal usually is targeted to the management of indi- soiling.
vidual symptoms, such as constipation, diarrhea, In large, randomized, double-blind, placebo- controlled trials involving patients with diarrhea- predominant IBS, the 5-HT –receptor antagonist alosetron at a dose of 1 mg twice a day for 12 In clinical practice, osmotic laxatives are often weeks decreased stool frequency and bowel ur- useful in the treatment of constipation, although gency, relieved abdominal pain and discomfort, they have not been studied in clinical trials spe- improved scores for global IBS symptoms (i.e., cifically involving patients with IBS. Fiber and adequate relief of IBS symptoms), and improved other bulking agents have also been used as initial health-related quality of life.24 Based on phase 2 therapy for constipation. However, the frequent trials suggesting that efficacy might be limited side effects (in particular, an increase in bloating) to female patients, subsequent trials for FDA ap- and inconsistent, largely negative results of trials proval included only women, and FDA approval of dietary fiber in the treatment of IBS have de- was limited to female patients with diarrhea- predominant IBS. A later study showed efficacy Tegaserod, a partial 5-hydroxytryptamine4 in men as well, although the indication has not (5-HT4 )–receptor agonist, has been shown in ran- been approved by the FDA.25 domized, clinical trials to be moderately effective In pooled analyses of female patients, alose- for global relief of symptoms in patients with IBS. tron was associated with an odds ratio for ade- In an analysis of eight randomized trials, patients quate relief of pain or global relief of symptoms assigned to tegaserod were 20% more likely to of 1.8 (95% confidence interval [CI], 1.6 to 2.1; have global relief of symptoms than those assigned number needed to treat for adequate symptom to placebo, with a number needed to treat of 17 to relief, 7.3). However, the FDA has restricted the achieve clinically significant global relief. However, use of the drug because of rare but serious ad- marketing of tegaserod was suspended in March verse effects occurring in both clinical trials and 2007, when an analysis of the data from clinical post-marketing studies, including complications trials identified a significant increase in the num- from constipation (ileus, bowel obstruction, fecal ber of cardiovascular ischemic events (myocardial impaction, and perforation; combined prevalence, infarction, stroke, and unstable angina) in patients 0.10% in the alosetron group vs. 0.06% in the taking the drug (13 events in 11,614 patients) as placebo group [from clinical trials dating up to compared with those receiving placebo (1 event in 2000])26 and ischemic colitis (prevalence, 0.15% 7031 patients); all events occurred in patients with in the alosetron group vs. 0.06% in the placebo known cardiovascular disease, cardiovascular risk group). Thus, alosetron is indicated only for wom- factors, or both.23 In July 2007, the Food and Drug en with severe diarrhea-predominant IBS who Administration (FDA) approved an investigational- have had symptoms for at least 6 months and new-drug program for tegaserod with access who have not had a response to conventional restricted to women younger than 55 years of therapies (in particular, antidiarrheal agents).
age who have constipation-predominant IBS (or chronic constipation) without known cardiovascu- Abdominal Pain Antispasmodic agents (e.g., hyoscyamine or me- beverine) have been used for the treatment of pain in patients with IBS. However, data from high- Although data from randomized trials of tradi- quality randomized, controlled trials of their ef- tional antidiarrheal agents in patients with diar- fectiveness in reducing pain or global symptoms rhea-predominant IBS are lacking, clinical expe- are lacking.22 n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e FDA-Approved
Evidence
lso not listed are serotonin–norepinephrine reuptake inhibitors.
el-designed clinical trials of effectiveness for global IB el-designed, controled clinical trials, and − no evidence. FD Syndrome
Irritable
Treatment
eta-analysis of such trials, +++ strong evidence from per Medication
2. Medications
any selective serotonin-reuptake inhibitors are available. O This list is not exhaustive but includes m (e.g., constipation, diarrhea, or abdom al controled trials or from Dosages A Lubiprostone Marketing have Alosetron Symptoms
Constipation
Diarrhea
Bloating
n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. Tricyclic antidepressant medications are com- There is a high prevalence of coexisting anxi- monly used for IBS symptoms, often in low doses ety in patients with IBS. Nevertheless, benzodiaz- (e.g., 10 to 75 mg of amitriptyline). Hypothesized epines are not recommended for long-term mediators of their effects include antihyperalge- therapy because of the risk of habituation and sia, improvement in sleep, normalization of gas- the potential for dependency.8 trointestinal transit,27 and when used at higher doses (e.g., 100 mg or more at bedtime), treat- Cognitive–Behavioral Therapy
ment of coexisting depression and anxiety. De- Cognitive–behavioral therapy (a combination of spite their frequent use in practice, data on the cognitive and behavioral techniques) is the best- efficacy of tricyclic antidepressants in patients studied psychological treatment for IBS.15,33 Cog- with IBS are inconsistent. Two meta-analyses (in- nitive techniques (typically administered in a cluding 11 randomized, controlled trials) showed group or an individual format in 4 to 15 sessions) that low-to-moderate doses of tricyclic antide- are aimed at changing catastrophic or maladap- pressants significantly reduced pain and overall tive thinking patterns underlying the perception symptoms in patients with IBS,1,28,29 but the of somatic symptoms.1,34 Behavioral techniques analyses have been criticized for the inclusion of aim to modify dysfunctional behaviors through studies that enrolled subjects with functional relaxation techniques, contingency management dyspepsia. A third meta-analysis that excluded (rewarding healthy behaviors), or assertion train- these studies showed that tricyclic antidepres- ing. Some randomized, controlled trials have also shown reductions in IBS symptoms with the use In the largest published randomized, placebo- of gut-directed hypnosis (aimed at improving gut controlled trial to date, treatment with desipra- function), which involves relaxation, change in mine (with an escalating dose from 50 to 150 mg) beliefs, and self-management.33,35 was not superior to placebo in intention-to-treat Data from head-to-head comparisons of psy- analyses. However, a secondary analysis (per pro- chotherapy with pharmacotherapy for IBS or psy- tocol) limited to patients with detectable plasma chotherapy plus pharmacotherapy with pharma- levels of desipramine showed a significant bene- cotherapy alone are lacking. The magnitude of fit over placebo.30 These patients presumably ad- improvement that has been reported with psycho- hered better to the protocol. Also, given the high logical treatments seems to be similar to or great- dose of desipramine that was studied, it is un- er than that reported with medications studied clear whether reported improvement in IBS symp- specifically for bowel symptoms in IBS, although toms was secondary to treatment of coexisting comparisons are limited by, among other things, depression or anxiety. Effects of tricyclic antide- the lack of a true placebo control in trials of pressants on sensitivity to somatic pain31 and psychotherapies. In a meta-analysis of 17 random- sleep suggest that they may have particular bene- ized trials of cognitive treatments, behavioral fit in patients with IBS who have widespread treatments, or both for IBS (including hypnosis), somatic pain or who sleep poorly, although this as compared with control treatments (including waiting list, symptom monitoring, and usual med- Several small, randomized, controlled trials ical treatment), those patients who were random- suggest that selective serotonin-reuptake inhibi- ly assigned to cognitive–behavioral therapy were tors may have beneficial effects in patients with significantly more likely to have a reduction in IBS, most commonly on measures of general gastrointestinal symptoms of at least 50% (odds well-being and, in some studies, on abdominal ratio, 12; 95% CI, 6 to 260),33 and the estimated pain.32 However, it remains unclear whether a number needed to treat with cognitive–behavioral lessening of depression or anxiety explains the therapy or hypnotherapy for one patient to have benefits. Although serotonin–norepinephrine re- improvement was estimated to be two.33 uptake inhibitors (duloxetine and venlafaxine) have been shown to be effective in reducing pain in other chronic pain conditions, including fibro- myalgia,11 data from randomized, controlled The optimal means of treating patients with trials of their role in the treatment of IBS are moderate or severe symptoms remains uncertain, particularly given the implementation of restrict- n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e ed-access programs for the newer pharmacother- Clinical experience suggests that mild symp- apies for diarrhea-predominant IBS and constipa- toms may be managed effectively by symptomatic treatment of altered bowel habits (e.g., antidiar- Limited data from small, randomized, con- rheal agents or laxatives). I find it helpful to trolled trials have suggested benefits of nonab- make it clear to the patient that I accept his or sorbable antibiotics36 (400 mg of rifaximin three her symptoms as real and to provide a patho- times a day), and probiotics,37,38 particularly for physiological explanation of symptoms.
symptoms of gas and bloating. More data are For severe diarrhea, as in the case described, needed from larger, high-quality randomized, I typically recommend starting a low daily dose controlled trials that assess the effects of these of loperamide (2 to 4 mg every morning, noting and other therapies, including antidepressant that this can be increased if the patient has a agents, and provide information on factors that particularly important activity), with the expecta- may predict responsiveness to these therapies. tion that this treatment may also decrease anxi- Lubiprostone (24 μg twice a day) has been ap- ety about having uncontrollable bowel movements proved by the FDA for the treatment of chronic during the day. Although the data from random- constipation and was recently shown to be effec- ized trials are conflicting with regard to the role tive in the treatment of constipation-predominant of tricyclic antidepressant agents in patients with IBS.39 The roles of this agent and other new IBS, I would also consider this therapy (e.g., ami- treatments for constipation and global relief of triptyline, starting at a dose of 10 mg at bedtime symptoms (e.g., linaclotide40) in constipation- and gradually, over a period of several weeks, predominant IBS remain to be established.
increasing to the maximum tolerated dose, but not higher than 75 mg at bedtime), making it clear to the patient that low-dose therapy is not aimed at altering mood but rather is aimed at Guidelines for the management of IBS have been reducing IBS symptoms, including abdominal issued by the American Gastroenterological Asso- pain. I would recommend participation in a cog- ciation,1 by the American College of Gastroenter- nitive–behavioral therapy program (ideally in the ology,15 by the Rome Foundation,2 and by the Brit- form of a brief, self-administered program),34 ish Society of Gastroenterology.14 Because of the although there are no data showing that the com- limited data from randomized trials involving pa- bination of cognitive–behavioral therapy and tients with IBS, these guidelines are based large- pharmacotherapy is superior to either treatment ly on consensus opinion. My recommendations alone in cases of IBS. If symptoms failed to im- are generally consistent with these guidelines.
prove sufficiently in this patient with diarrhea, I would discuss with her the potential addition of Summ ary and R ecommendations alosetron, but with attention to its potential for rare serious adverse effects, including ischemic In patients such as the woman in the vignette, colitis.14 who present with symptoms suggestive of IBS, Supported by grants (P50 DK64539, R24 AT002681, R01 including chronic abdominal pain and discomfort DK48351, and R01 DK58173) from the National Institutes of associated with diarrhea, the first step in evalua- Health.
tion is a careful history taking to rule out warn- Dr. Mayer reports receiving research support from Glaxo- SmithKline, Novartis, and Avera and consulting fees from Boeh- ing signs, including unexplained weight loss and ringer Ingelheim, Johnson & Johnson, Prometheus, Dannon, and hematochezia. In the absence of any warning Nestlé. No other potential conflict of interest relevant to this signs, the diagnosis usually can be made clini- article was reported.
I thank Teresa Olivas and Cathy Liu for invaluable assistance cally without the need for further testing (Fig. 1). in preparing the manuscript, and Lin Chang, Douglas Dross- I would also determine whether a gastrointestinal man, Jeff Lackner, and Brennan Spiegel for valuable com- infection or any major life event preceded the re- ments.
cent flare of symptoms, since these are common An audio version of this article is available at www.nejm.org.
n engl j med 358;16 www.nejm.org april 17, 2008 Downloaded from www.nejm.org by SOFA BERGERET MD on January 25, 2010 . Copyright 2008 Massachusetts Medical Society. All rights reserved. References
1. Drossman DA, Camilleri M, Mayer EA, et al. Systematic review on the manage-
28. Jackson JL, O’Malley PG, Tomkins G,
Whitehead WE. AGA technical review on ment of irritable bowel syndrome in North Balden E, Santoro J, Kroenke K. Treat- irritable bowel syndrome. Gastroenterol- America. Am J Gastroenterol 2002;97: ment of functional gastrointestinal disor- 2. Longstreth GF, Thompson WG, Chey 16. Cash BD, Schoenfeld P, Chey WD. The a meta-analysis. Am J Med 2000;108:65-
WD, Houghton LA, Mearin F, Spiller RC. utility of diagnostic tests in irritable bow- 72.
Functional bowel disorders. In: Drossman el syndrome patients: a systematic review. 29. Lesbros-Pantoflickova D, Michetti P,
DA, Corazziari E, Delvaux M, et al., eds. Am J Gastroenterol 2002;97:2812-9.
Rome III: the functional gastrointestinal 17. Spiegel BM, DeRosa VP, Gralnek IM, analysis: the treatment of irritable bowel
disorders. 3rd ed. McLean, VA: Degnon, Wang V, Dulai GS. Testing for celiac sprue syndrome. Aliment Pharmacol Ther 2004; in irritable bowel syndrome with predom- 20:1253-69.
3. Halder SL, Locke GR III, Schleck CD, inant diarrhea: a cost-effectiveness analy-
30. Drossman DA, Toner BB, Whitehead
Zinsmeister AR, Melton LJ III, Talley NJ. sis. Gastroenterology 2004;126:1721-32.
WE, et al. Cognitive-behavioral therapy ver- Natural history of functional gastrointes- 18. Hamm LR, Sorrells SC, Harding JP, sus education and desipramine versus
tinal disorders: a 12-year longitudinal et al. Additional investigations fail to alter placebo for moderate to severe functional population-based study. Gastroenterology the diagnosis of irritable bowel syndrome bowel disorders. Gastroenterology 2003; in subjects fulfilling the Rome criteria. 125:19-31.
4. Whitehead WE, Palsson O, Jones KR. Am J Gastroenterol 1999;94:1279-82.
31. Saarto T, Wiffen PJ. Antidepressants
Systemic review of the comorbidity of irri- 19. Spiegel BM, Naliboff B, Mayer E, Bolus for neuropathic pain. Cochrane Database
table bowel syndrome with other disorders: R, Gralnek I, Shekelle P. The effectiveness Syst Rev 2005;3:CD005454.
what are the causes and implications? of a model physician-patient relationship 32. Mayer EA, Tillisch K, Bradesi S. Modu-
versus usual care in irritable bowel syn- lation of the brain-gut axis as a therapeu- 5. Wessely S, White PD. There is only one drome (IBS): a randomized controlled trial. tic approach in gastrointestinal disease.
functional somatic syndrome. Br J Psychia- Gastroenterology 2006;130:Suppl 2:A-112. Aliment Pharmacol Ther 2006;24:919-33.
33. Lackner JM, Mesmer C, Morley S,
6. Spiegel BM, Gralnek IM, Bolus R, et al. 20. Ilnyckyj A, Graff LA, Blanchard JF, Dowzer C, Hamilton S. Psychological treat-
Clinical determinants of health-related Bernstein CN. Therapeutic value of a gas- ments for irritable bowel syndrome: a sys- quality of life in patients with irritable troenterology consultation in irritable tematic review and meta-analysis. J Con- bowel syndrome. Arch Intern Med 2004; bowel syndrome. Aliment Pharmacol Ther sult Clin Psychol 2004;72:1100-13.
34. Lackner JM, Jaccard J, Krasner SS,
7. Levy RL, Von Korff M, Whitehead WE, 21. FDA permits restricted use of Zel-
et al. Costs of care for irritable bowel syn- norm for qualifying patients. News release administered cognitive behavior therapy drome patients in a health maintenance of the Food and Drug Administration, for moderate to severe IBS: clinical effi- organization. Am J Gastroenterol 2001;96: Rockville, MD, July 27, 2007. (Accessed cacy, tolerability, feasibility. Clin Gastro- March 24, 2008, at http:/ www.fda.gov/ enterol Hepatol (in press).
8. Di Lorenzo C, Rasquin A, Forbes D, et bbs/topics/NEWS/2007/NEW01673.html.)
35. Whorwell PJ. The history of hypno-
al. Childhood functional gastrointestinal 22. Tack J, Fried M, Houghton LA, Spicak therapy and its role in the irritable bowel
disorders: child/adolescent. In: Drossman J, Fisher G. Systematic review: the efficacy syndrome. Aliment Pharmacol Ther 2005; DA, Corazziari E, Delvaux M, et al., eds. of treatments for irritable bowel syndrome 22:1061-7.
Rome III: the functional gastrointestinal — a European perspective. Aliment Phar- 36. Pimentel M, Park S, Mirocha J, Kane
disorders. 3rd ed. McLean, VA: Degnon, macol Ther 2006;24:183-205.
23. Pasricha PJ. Desperately seeking sero-
9. Spiller R, Campbell E. Post-infectious tonin. . . . A commentary on the with-
irritable bowel syndrome. Curr Opin Gas- drawal of tegaserod and the state of drug a randomized trial. Ann Intern Med 2006; development for functional and motility 145:557-63.
10. Mayer EA, Craske MG, Naliboff BD. disorders. Gastroenterology 2007;132:2287-
37. O’Mahony L, McCarthy J, Kelly P, et al.
Depression, anxiety, and the gastrointes- 90.
Lactobacillus and bifidobacterium in irri- tinal system. J Clin Psychiatry 2001;62: 24. Bradesi S, Tillisch K, Mayer E. Emerg- table bowel syndrome: symptom respons-
ing drugs for irritable bowel syndrome. Ex- es and relationship to cytokine profiles. 11. Gershon MD, Tack J. The serotonin pert Opin Emerg Drugs 2006;11:293-313.
signaling system: from basic understand- 25. Chang L, Ameen VZ, Dukes GE, Mc- 38. Quigley EM, Flourie B. Probiotics and
ing to drug development for functional GI Sorley DJ, Carter EG, Mayer EA. A dose- irritable bowel syndrome: a rationale for disorders. Gastroenterology 2007;132:397- ranging, phase II study of the efficacy and their use and an assessment of the evi- safety of alosetron in men with diarrhea- dence to date. Neurogastroenterol Motil 12. Mayer EA, Gebhart GF. Basic and predominant IBS. Am J Gastroenterol 2007;19:166-72.
clinical aspects of visceral hyperalgesia. 2005;100:115-23.
39. Johanson JF, Drossman DA, Panas R,
26. Chang L, Chey WD, Harris L, Olden K, Wahle A, Ueno R. Clinical trial: phase 2
13. Kassinen A, Krogius-Kurikka L, Mäki-
Surawicz C, Schoenfeld P. Incidence of trial of lubiprostone for irritable bowel vuokko H, et al. The fecal microbiota of ischemic colitis and serious complications syndrome with constipation. Aliment Phar- irritable bowel syndrome patients differs of constipation among patients using alo- macol Ther (in press).
significantly from that of healthy subjects. steron: systematic review of clinical trials 40. Andresen V, Camilleri M, Busciglio
and post-marketing surveillance data. Am IA, et al. Effect of 5 days linaclotide on 14. Spiller R, Aziz Q, Creed F, et al. Guide-
transit and bowel function in females with lines on the irritable bowel syndrome: 27. Clouse RE, Lustman PJ. Use of psycho- constipation-predominant irritable bow-
mechanisms and practical management. pharmacological agents for functional gas- el syndrome. Gastroenterology 2007;133: trointestinal disorders. Gut 2005;54:1332- 761-8.
15. Brandt LJ, Bjorkman D, Fennerty MB, 41.
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