Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in Primary Care

Transcription

1 Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in Primary Care May 1, 2013 Anaheim, California Educational Partner:

2 Session 5: Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in Primary Care Learning Objectives 1. Diagnose irritable bowel syndrome (IBS) based on symptoms that may be shared with other functional gastrointestinal disorders or organic diseases. 2. Compare and contrast the efficacy and safety of available pharmacologic and nonpharmacologic treatment options for IBS. 3. Apply appropriate and comprehensive treatment strategies to enhance the care of patients with IBS. Faculty Lawrence R. Schiller, MD, FACS Professor of Internal Medicine Texas A&M Health Science Center, Dallas Campus Program Director Gastroenterology Fellowship Baylor University Medical Center Dallas, Texas Lawrence R. Schiller, MD, FACS, was born in Philadelphia and attended Pennsylvania State University and Jefferson Medical College of Philadelphia. He completed his internal medicine training at Temple University Hospital, also in Philadelphia, and then served 2 years in the U.S. Army Medical Corps. Dr Schiller moved to Texas in 1978 for gastroenterology training at the University of Texas (UT) Southwestern Medical Center, where he remained on the faculty at the medical school; he also spent 5 years as an attending physician at the Dallas VA Hospital. In 1985, Dr Schiller moved to Baylor University Medical Center to continue research activities with Dr John Fordtran, and has been there ever since, most recently serving as program director for the Gastroenterology Fellowship. Dr Schiller has been involved in patient care as a founding partner of Digestive Health Associates of Texas, one of the largest single-specialty gastroenterology practices in the United States, and has continued with research and education activities at Baylor and UT Southwestern. He is currently an attending physician and chairman of the Institutional Review Board for Human Subject Protection at Baylor, as well as clinical professor of internal medicine at UT Southwestern, where he has won 2 fellow teaching awards. Dr Schiller has been elected to fellowships in the American College of Physicians and the American College of Gastroenterology (ACG) and has served as ACG governor of the North Texas region. Currently serving as ACG president, he has also served as president of the Texas Society for Gastroenterology and Endoscopy. Dr Schiller has published more than 80 papers and 45 book chapters dealing with gastric physiology, intestinal transport, diarrheal diseases, and motility disorders. Brian E. Lacy, MD, PhD Professor of Medicine Geisel School of Medicine at Dartmouth College Hanover, New Hampshire Director, Gastrointestinal Motility Laboratory Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire Brian E. Lacy, MD, PhD, is currently professor of medicine at the Geisel School of Medicine at Dartmouth College in Hanover, New Hampshire. He is also section chief of the Division of Gastroenterology and Hepatology, and director of the Gastrointestinal Motility Laboratory at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. Dr Lacy s clinical and basic science research interests focus on disorders of gastrointestinal (GI) motility, with an emphasis on IBS, dyspepsia, gastroparesis, acid reflux disease, constipation, intestinal pseudo-obstruction, achalasia, and visceral pain. He is Session 5

3 the author or coauthor of more than 85 peer-reviewed articles, the author or coauthor of numerous textbook chapters on GI motility disorders and functional bowel disorders, and a reviewer for a number of scientific journals. Dr Lacy is coauthor of Healing Heartburn, a book for the general public on acid reflux disease; is the author of Making Sense of IBS, a book for the general public on irritable bowel syndrome; and is the editor and author of Curbside Consultations in IBS: 49 Clinical Questions. Dr Lacy is a member of the American College of Gastroenterology, the American Gastroenterology Association, the American Motility Society, and the Rome Committee. Dr Lacy earned his doctorate in cell biology from Georgetown University in Washington, DC, and his medical degree from the University of Maryland in Baltimore. He completed a residency in internal medicine at Dartmouth-Hitchcock, where he continued his training as chief resident and then as a fellow in gastroenterology. He is board-certified in gastroenterology. Faculty Financial Disclosure Statements The presenting faculty reported the following: Dr Schiller is a speaker for Ironwood Pharmaceuticals, Inc.; Forest Laboratories, Inc.; and Takeda Pharmaceutical Company Limited; and consultant for Synergy Pharmaceuticals, Inc. Dr Lacy serves as scientific advisory board member for Ironwood Pharmaceuticals, Inc.; Salix Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Limited. Education Partner Financial Disclosure Statement The content collaborators at CME Incite have reported the following: Rose O Connor, PhD, and Monique Pond, PhD, have no financial relationships to disclose. Suggested Reading List Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106(3): ; quiz 515. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1-S35. Cash BD, Chang E, Talley NJ, et al. Fresh perspectives in chronic constipation and other functional bowel disorders. Rev Gastroenterol Disord. 2007;7(3): Ford AC, Talley NJ. IBS in 2010: advances in pathophysiology, diagnosis and treatment. Nat Rev Gastroenterol Hepatol. 2011;8(2): Halpert A, Dalton CB, Palsson O, et al. What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol. 2007;102(9): Hasler WL. Traditional thoughts on the pathophysiology of irritable bowel syndrome. Gastroenterol Clin North Am. 2011;40(1): Johannesson E, Simrén M, Strid H, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106(5): Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010;139(6): Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130(5): Pimentel M, Lembo A, Chey WD, et al; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1): Session 5

4 SESSION 5 2:45 PM 4:00 PM Under Pressure: The Need to Expedite IBS Diagnosis and Treatment in Primary Care SPEAKERS Lawrence R. Schiller, MD, FACS Brian E. Lacy, MD, PhD Presenter Disclosure Information The following relationships exist related to this presentation: Dr Schiller is a speaker for Ironwood Pharmaceuticals, Inc.; Forest Laboratories, Inc.; and Takeda Pharmaceutical Company Limited; and consultant for Synergy Pharmaceuticals, Inc. Dr Lacy serves as scientific advisory board member for Ironwood Pharmaceuticals, Inc.; Salix Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Limited. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Lawrence R. Schiller, MD, FACG Digestive Health Associates of Texas Baylor University Medical Center Dallas, Texas Brian E. Lacy, MD, PhD Professor of Medicine Dartmouth Medical School Hanover, New Hampshire Director of the GI Motility Laboratory Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire Diagnose IBS based on symptoms that may be shared with other functional GI disorders or organic diseases Compare and contrast the efficacy and safety of available pharmacologic and nonpharmacologic treatment options for IBS Apply appropriate and comprehensive treatment strategies to enhance the management of patients with IBS IBS, irritable bowel syndrome; GI, gastrointestinal. A3309 Alosetron Amitriptyline Atropine Cholestyramine Citalopram Desipramine Diphenoxylate Doxepin Fluoxetine Hyoscyamine Imipramine Linaclotide Loperamide Lubiprostone Paroxetine Prucalopride Psyllium Rifaximin No trade name Lotronex Elavil, Tryptizol, Laroxyl, etc Sal-tropine Questran Celexa Norpramin, Pertofane Lomotil, Lonox, Dimotal, etc Adapin, Silenor, Sinequan, etc Prozac, Sarafem, Fontex, etc A-Spas, Anapaz, Cytospaz, etc Antideprin, Deprimin, Deprinol, etc Linzess Imodium, Diar-Aid, Diamode, etc Amitiza Paxil, Aropax, Seroxat, Pexeva, etc Resolor Fiberall, Benefiber, Metamucil, etc Xifaxan 1. None 2. 1 to to to to to to >60 1

5 A 43-year-old patient presents with IBS symptoms for >3 months prior to initial visit without the presence of alarm features. What should be your next course of action 1. Watch and wait for emergence of alarm features 2. Perform routine lab tests (CBC, CMP, TSH, stool O+P, abdominal imaging) 3. Refer for colonoscopy 4. Begin treatment for IBS immediately 5. Unsure How would you distinguish IBS from other functional GI disorders, such as functional constipation (FC) or functional diarrhea (FD) 1. Pain is more prominent than bowel disturbance in FC or FD 2. Pain is more prominent than bowel disturbance in IBS 3. Frequency of bowel habits differs between FC/FD and IBS 4. Changes in diet have more impact on patients with IBS than on patients with FC or FD 5. Unsure CBC, complete blood count; CMP, comprehensive metabolic panel; TSH, thyroid-stimulating hormone, O+P, ova and parasites. Which of the following therapies is an evidencebased treatment option for patients with IBS-C 1. Hyoscyamine 2. Lubiprostone 3. Loperamide 4. Alosetron 5. Unsure What medication would you recommend for a 57-year-old woman with severe IBS-D who has previously tried anticholinergics, loperamide, SSRIs, and dietary changes, but still has abdominal pain and urgency 1. Diphenoxylate with atropine 2. Lubiprostone 3. Polyethylene glycol 4. Alosetron 5. Any of the above 6. Unsure IBS-C, IBS Constipation. IBS-D, IBS Diarrhea; SSRIs, selective serotonin reuptake inhibitors; PEG, polyethylene glycol. Which of the following mechanistic effects is thought to be influenced by the use of probiotics 1. Immune function 2. Anti-inflammatory effects 3. Alteration of local ph 4. All of the above 5. Unsure 2

6 AC, a 45-year-old woman, presents with a 6-year history of abdominal pain and variable bowel habits Crampy pain is located in left lower quadrant Pain peaks just before bowel movement Pain is relieved by defecation Bowel movements vary in consistency from loose to hard Frequency of bowel movements varies from once weekly to 4 times per day Other symptoms include indigestion, early satiety, bloating, excessive flatulence, and belching Patient has experienced no weight loss or rectal bleeding Previous evaluation included colonoscopy with biopsies (negative), endoscopy with biopsies (negative), and abdominal sonogram (negative) Patient has tried lactose-free diet, increased dietary fiber, dicyclomine, and hyoscyamine, all without benefit Physical examination is unremarkable 1. Past surgical history 2. History of migraine headaches 3. Discussion of life stressors and relation to symptoms 4. Discussion of physical and sexual abuse 5. Family history of digestive symptoms 1. Laboratory tests: CBC, CMP, TSH 2. Pelvic examination 3. Diet and symptom diary for 2 weeks 4. CT scan of abdomen/pelvis 5. Repeat colonoscopy and endoscopy Lawrence R. Schiller, MD, FACG Worldwide prevalence: 7% to 10% 1.5 times more prevalent in women More commonly diagnosed in patients <50 years of age More common in lower socioeconomic groups Patients with IBS have more physician visits, more hospitalizations, more missed workdays, more prescriptions, and more diagnostic tests than those without the disorder American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35. 3

7 IBS is a syndrome a collection of symptoms Diagnosis is possible by taking a thorough history of symptoms Since symptoms may be due to other disorders, the provider must consider alternative organic diagnoses Serious organic illnesses typically produce alarm symptoms Abdominal pain Anywhere in abdomen Characteristically relieved by defecation Altered stool frequency Excess frequency: >2 bowel movements/day Infrequency: <3 bowel movements/week Altered stool form Loose to lumpy Hard or Lumpy Stools (%) IBS-C IBS-U IBS-M IBS-D Loose or Watery Stools (%) IBS-C: Constipation-predominant IBS IBS-D: Diarrhea-predominant IBS IBS-M: Mixed IBS (hard and loose stools over periods of weeks and months) IBS-U: Unsubtyped IBS Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with 2 of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form of stool Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis Additional IBS testing, including routine laboratory tests and colonoscopy, unnecessary unless alarm features present Longstreth GF, et al. Gastroenterology. 2006;130(5): ; erratum in: Gastroenterology. 2006;131(2):688. Longstreth GF, et al. Gastroenterology. 2006;130(5): ; erratum in: Gastroenterology. 2006;131(2):688. Refractory or worsening abdominal symptoms Older patient ( 50 years of age; 45 years of age if African American) Blood in stools Anemia Weight loss (unintentional) Anorexia Family history of organic GI disease Further investigation warranted Consider colonoscopy Routine laboratory tests (CBC, CMP) and TSH, stool O+P, abdominal imaging not recommended Serologic testing for celiac disease (IBS-D/M) recommended Lactose breath testing selected cases Colonoscopy recommended if >50 years of age, with biopsies in refractory IBS-D (to exclude microscopic colitis) ACG, American College of Gastroenterology. Lembo A, Camilleri M. N Engl J Med. 2003;349(14): ; Brandt LJ, et al. Am J Gastroenterol. 2005;100(suppl 1):S5- S21; Cash BD, et al. Rev Gastroenterol Disord. 2007;7(3): American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35. 4

8 Dysmotility Hypersensitivity Disordered brain processing Enteric nervous system dysfunction SERT activity Postinfectious IBS Somatization syndrome Small intestinal bacterial overgrowth Mast cell dysfunction Dysbiosis Food intolerances Food allergy Genetics SERT, serotonin transporter. Hasler WL. Gastroenterol Clin North Am. 2011;40(1):21-43; Ford AC, Talley NJ. Nat Rev Gastroenterol Hepatol. 2011;8(2): Other functional GI disorders Functional constipation, functional diarrhea Pain less prominent than bowel disturbance Functional abdominal pain Bowel disturbance less prominent Gastrointestinal Colorectal cancer Diverticular disease Gynecologic Ovarian cancer Endometriosis Drugs Opiates Anticholinergics Antidepressants Metabolic/endocrine Hypothyroidism Diabetes Neurologic Parkinson s disease Multiple sclerosis Autonomic neuropathy Other Amyloidosis Scleroderma Candelli M, et al. Hepatogastroenterology. 2001;48(40): ; Locke GR III, et al. Gastroenterology. 2000;119(6): Dietary factors Lactose Gluten Other FODMAPs Drugs Infection Giardiasis Amebiasis Malabsorption Celiac disease FODMAPs, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Inflammatory bowel disease Crohn s disease Ulcerative colitis Microscopic colitis Psychological Panic disorder Somatization Depression Candelli M, et al. Hepatogastroenterology. 2001;48(40): ; Locke GR III, et al. Gastroenterology. 2000;119(6): Identify IBS symptoms, presence of alarm features Meets criteria, no alarm features make diagnosis of IBS Doesn t meet criteria, has alarm features look for alternative diagnosis Symptomatic treatment for predominant symptoms Good response continue Rx Assess response to treatment Poor response reassess Longstreth GF, et al. Gastroenterology. 2006;130(5): ; erratum in: Gastroenterology. 2006;131(2):688; American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S35. 5

9 A 43-year-old patient presents with IBS symptoms for >3 months prior to initial visit without the presence of alarm features. What should be your next course of action 1. Watch and wait for emergence of alarm features 2. Perform routine lab tests (CBC, CMP, TSH, stool O+P, abdominal imaging) 3. Refer for colonoscopy 4. Begin treatment for IBS immediately 5. None of the above 6. Unsure How would you distinguish IBS from other functional GI disorders, such as functional constipation (FC) or functional diarrhea (FD) 1. Pain is more prominent than bowel disturbance in FC or FD 2. Pain is more prominent than bowel disturbance in IBS 3. Frequency of bowel habits differs between FC/FD and IBS 4. Changes in diet have more impact on patients with IBS than on patients with FC or FD 5. Unsure Brian E. Lacy, MD, PhD Psychological treatments Goal: improved function Continuing care + Follow-up visit Manage stress Drug therapy + Diet, lifestyle advice Positive diagnosis Explain, reassure Severe (25%) Moderate (35%) Mild (40%) Francis CY, Morris J, Whorwell PJ. Aliment Pharmacol Ther. 1997;11: Drossman DA, et al. Am J Gastroenterol. 2011;106: Lifestyle 1 Survey of 1242 patients: following interventions improved symptoms Small meals (69%), avoiding fat (64%), increasing fiber (58%), avoiding milk products (54%) Food allergy 2 limited evidence Lactose 3 higher % of lactose maldigestion Gluten 4,5 studies indicate possible link Fructose intolerance 6 studies indicate possible link Treatment Modality Studies, N 1. Halpert A, et al. Am J Gastroenterol. 2007;102: Locke GR 3 rd, et al. Am J Gastroenterol. 2200;95: *Total GI symptom severity measured at 1 year compared to baseline values in gut-directed hypnotherapy group. 3. Brandt LJ, et al. Am J Gastroenterol. 2009;104(suppl 1):S1-S Wahnschaffe U, et al. Clin Gastroenterol Hepatol. 2007;5: Biesiekierski JR, et al. Am J Gastroenterol. 2011;106: Shepherd SJ, et al. J Am Diet Assoc. 2006;106: Ford AC, et al. Gut. 2009;58: Lindfors P, et al. Am J Gastroenterol. 2012;107: Pts N C RR (95% CI) Cognitive behavioral therapy (CBT) ( ) Multicomponent psychological therapy ( ) Stress management ( ) Dynamic psychotherapy ( ) Hypnotherapy P<0.01* 6

10 Abdominal pain/discomfort Antispasmodics* Antidepressants* TCAs/SSRIs Alosetron (5HT-3 antagonist) Lubiprostone (chloride channel activator) Linaclotide (guanylate cyclase-c agonist) Abdominal pain/ discomfort Bloating/ distension Bloating Rifaximin* Probiotics Constipation Fiber* MOM/PEG solution* Lubiprostone (chloride channel activator) Linaclotide (guanylate cyclase-c agonist) Altered bowel function *These agents are not currently FDA-approved for IBS. TCAs, tricyclic antidepressants. Diarrhea Loperamide* Diphenoxylateatropine* Cholestyramine* Alosetron Rifaximin* Brandt LJ, et al. Am J Gastroenterol. 2002;97(11 suppl):s7-s26. Drossman DA, et al. Gastroenterology. 2002;123: Randomized, placebo-controlled trial (N=275 patients with IBS) Primary endpoint: adequate symptom relief 2 weeks in previous month, analyzed after 1, 2, and 3 months RESULT Higher % responders in psyllium vs placebo group during first month (57% vs 35%) Higher % responders through 2 months of treatment (59% vs 41%) No significant improvement was noted in measurement of abdominal pain relief No adult studies of laxatives in IBS-C 1 27 adolescents: PEG improved number of bowel movements (P<0.05) but not pain in IBS-C patients #BMs Pain Level Pre- Treatment Post- Treatment Bijkerk CJ, et al. BMJ. 2009;339: Brandt L, et al. Am J Gastroenterol. 2009;104(suppl):S1-S Khoshoo V, et al. Aliment Pharmacol Ther. 2006;23: Phase 3 12-week randomized controlled trials Results: patients receiving lubiprostone (8 μg BID) twice as likely to achieve overall response 7.8% difference (P=0.001) vs placebo % Placebo n= % Lubiprostone n=783 Ensure absence of mechanical obstruction before beginning therapy Drossman DA, et al. Aliment Pharmacol Ther. 2009;29: Responder (%) % Responders FDA Primary Endpoint ( 6/12 Weeks) Placebo (n=403) *P< for all analyses of linaclotide vs placebo groups, using Cochran-Mantel-Haenszel test Chey WD, et al. Am J Gastroenterol. 2012; epub September 18. Linaclotide 290 μg (n=401) FDA Primary Endpoint: 30% reduction worst abdominal pain and increase 1 CSBM, both for 6/12 weeks 7

11 % Change in Worst Abdominal Pain Linaclotide 290 µg Placebo -60 BL Trial Week N=804 ITT population, observed cases, LS-means presented: P-values based on ANCOVA P= for Week 1 P< for Weeks 2-26 at each week. Bars represent 95% CI. Diarrhea is the most common adverse event associated with linaclotide treatment; other AEs were comparable between placebo and linaclotide treatment groups. Chey WD, et al. Am J Gastroenterol. 2012; epub September 18. Low doses 2 mg once or twice daily may be effective to decrease stool frequency, improve stool consistency 2 randomized controlled trials in IBS (N=42) show efficacy for diarrhea No impact on symptoms of abdominal discomfort, bloating, or global IBS Adverse effects: dizziness, abdominal pain/bloat, constipation, dry mouth, fatigue Study N Female, % Response: Alosetron, % Response: Placebo, % Therapeutic Gain, % Camilleri Camilleri Camilleri Lembo Jones 5 * *Comparison mebeverine instead of placebo. Mebeverine not available in the US. Accessed May 15, Camilleri M, et al. Aliment Pharmacol Ther. 1999;13: Camilleri M, et al. Lancet. 2000;355: Camilleri M, et al. Arch Intern Med. 2001;161: Lembo T, et al. Am J Gastroenterol. 2001;96: Jones R, et al. Aliment Pharmacol Ther. 1999;13: Female patients with chronic, severe IBS-D who failed other treatments Dose: mg QD to BID Patient education regarding possible serious adverse effects of severe constipation or ischemic colitis 0.95 cases of ischemic colitis/1000 patient-years 0.36 cases of severe constipation/1000 patient-years Ischemic colitis usually occurs within the first month of therapy if it occurs Prescribing program mandated by FDA Requires patient to sign attestation form Lactobacilli anerobic, gram (+) rods casei plantarum acidophilus reuteri Bifidobacteria anerobic, gram (+) rods VSL #3 (8 separate organisms: 3 Bifidobacteria, 1 Streptococcus, 4 Lactobacilli) Enterococcus Streptococcus salivarius Saccharomyces Accessed May 15, Moayyedi P, et al. Gut. 2010:59: Epub 2008 Dec 17. 8

12 Competitive inhibition Barrier protection Immune effects Anti-inflammatory effects Production of various substances (enzymes, SCFA, bacteriocidal agents) Ability to alter local ph and physiology Provides nutrition to colonocytes Answering Yes at Week 4 (%) P= B Infantis B Infantis B Infantis Placebo 1 x x x 10 6 SGA (Subjects Global Assessment) a yes/no response to the following question: Please consider how you felt in the past week in regard to your IBS, in particular your general well being, and symptoms of abdominal discomfort or pain, bloating or distension, and altered bowel habit. Compared with the way you felt before beginning the medication, have you had adequate relief of your IBS symptoms Camilleri M. J Clin Gastroenterol. 2006;40: Whorwell PJ, et al. Am J Gastroenterol. 2006;101: randomized controlled trials comparing 12 different antispasmodics vs placebo (N=1778 patients) Significant heterogeneity among studies Many agents not available in US Appear most useful for abdominal pain In meta-analysis, symptoms persist in 39% of patients receiving antispasmodics vs 56% of placebo-treated patients (RR: 0.68; 95% CI: ) Ford AC, et al. BMJ. 2008;337:a2313. TCAs: 9 studies (N=319 drug vs 256 control) Imipramine, desipramine, amitriptyline, doxepin*; doses mg Meta-analysis favors treatment SSRIs: 5 studies (N=113 drug vs 117 control) Fluoxetine, paroxetine, citalopram*; dose mg Meta-analysis favors treatment *These agents are not currently FDA-approved for IBS. Ford AC, et al. Gut. 2009;58:

13 2 Phase 3 randomized controlled trials; N=1260 patients Rifaximin 550 mg TID x 2 weeks; patients followed additional 10 weeks 40.7% vs 31.7% with adequate relief of global symptoms (P<0.001) T-I T-II Comb Rifaximin Placebo Not systemically absorbed Doses studied for IBS: 400 mg BID to 550 mg TID Primary adverse effects include headache, abdominal pain, and upper respiratory tract infection T-I, TARGET 1 trial; T-II, TARGET 2 trial; Comb, Combination of both trials. *Rifaximin is not currently FDA-approved for IBS. Pimentel M, et al. N Engl J Med. 2011;364: Ford AC, et al. Clin Gastroenterol Hepatol. 2009;7: Pimentel M, et al. N Engl J Med. 2011;364: Treatment depends on severity of IBS symptoms Management of diet, exercise, and sleep build foundation for success of other therapies Limited evidence but useful starting points Pharmacologic therapies directed at predominant symptoms Evidence-based treatments include IBS-C: lubiprostone, linaclotide, SSRIs IBS-D: alosetron, TCAs Probiotics may help with bloating Centrally acting therapies (eg, antidepressants) in select patients may help with improving general well being Novel agents in development Rifaximin is a promising therapy for IBS-D Which of the following therapies is an evidencebased treatment option for patients with IBS-C 1. Hyoscyamine 2. Lubiprostone 3. Loperamide 4. Alosetron 5. Unsure What medication would you recommend for a 57-year-old woman with severe IBS-D who has previously tried anticholinergics, loperamide, SSRIs, and dietary changes, but still has abdominal pain and urgency 1. Diphenoxylate with atropine 2. Lubiprostone 3. Polyethylene glycol 4. Alosetron 5. Any of the above 6. Unsure Which of the following mechanistic effects is thought to be influenced by the use of probiotics 1. Immune function 2. Anti-inflammatory effects 3. Alteration of local ph 4. All of the above 5. Unsure 10

14 Jenny, a 27-year-old waitress, presents for a second opinion 6-year history of lower abdominal pain, cramps, and urgent diarrhea Occasional episodes of urgent incontinence Stable weight No family history of IBD or celiac disease Normal CBC, ESR, celiac serologies, and stool studies Normal flexible sigmoidoscopy with biopsies Lactose-free diet did not help Gluten-free diet x2 months did not help FODMAP diet x2 months did not help Imodium helps diarrhea a little, but no help with urgency or lower abdominal pain Diphenoxylate-atropine caused fatigue and palpitations Rifaximin was suggested, but her insurance company would not approve it 1. Appeal insurance company decision on rifaximin denial 2. Prescribe cholestyramine 1 g QD 3. Prescribe alosetron 0.5 mg QD 4. Prescribe alosetron 1 mg BID 5. Prescribe a SSRI 11