10/1/2016. Kimberly Kearns, MS, APN, ANP-BC Mary Davitt, MS, PMHNP-BC Rachel Richardson, RD. Kimberly Kearns, APN. Mary Davitt, PMHNP.

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Speakers Bureau: Medtronic Salix Pharmaceuticals Takeda

Richardson, RD None Discuss epidemiology and

diagnostic criteria of irritable bowel syndrome Explore

1 Kimberly Kearns, MS, APN, ANP-BC Mary Davitt, MS, PMHNP-BC Rachel Richardson, RD Kimberly Kearns, APN Speakers Bureau: Medtronic Salix Pharmaceuticals Takeda Pharmaceuticals Mary Davitt, PMHNP None Rachel Richardson, RD None Discuss epidemiology and pathophysiology of irritable bowel syndrome Review diagnostic criteria of irritable bowel syndrome Explore gastroenterology, psychology and dietary approaches to the management of irritable bowel syndrome 1

Irritable bowel syndrome (IBS) is a chronic gastrointestinal

distention, flatulence, and bowel disturbances.

com/us/irritable-bowel-syndrome/epidemiology 30 % of all referrals to

7 th most common dx by primary care providers 2 nd highest cause of

life scores lower than Diabetes mellitus Hypertension End-stage renal

2 Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition that may be characterized by abdominal pain, bloating, distention, flatulence, and bowel disturbances. Affects an estimated 35 million people in the United States World wide prevalence of 11.2 % 2:1 female predominance in North America drschaer-institute.com/us/irritable-bowel-syndrome/epidemiology 30 % of all referrals to gastroenterologists Most commondiagnosis in clinical gastroenterology 7 th most common dx by primary care providers 2 nd highest cause of work absenteeism Effect on quality of life Health-related quality of life scores lower than Diabetes mellitus Hypertension End-stage renal disease Increased health care costs Direct/indirect costs up to $30 billion Drossman et al, Gastroenterolgy 2002; 123 (6): 2108 Ford et al, Am. J. Gastro

Presence of recurrent abdominal pain: At least 1 day/week for the last 3 months

with a change in stool frequency Associated with a change in stool

Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology.

3 Presence of recurrent abdominal pain: At least 1 day/week for the last 3 months With 2 or more of the following characteristics: Related to defecation Associated with a change in stool frequency Associated with a change in stool form/appearance Symptoms must have started at least 6 months before diagnosis Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6): Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):

4 Incompletely understood Interactions among a number of factors and is overall complex GI Motility Visceral Hypersensitivity Increased Permeability Immune Activation Pathophysiology: Irritable Bowel Syndrome Genetic Diet Psychological Factors Gut Microbiome Brain-Gut Axis 4

GI Motility Increase in frequency and irregularity of luminal contents Prolonged transit time (IBS-C) Exacerbated response to cholecystokinin (IBS-D) Meal ingestion (IBS-D) Visceral

brain Brain-Gut Axis Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology.

5 GI Motility Increase in frequency and irregularity of luminal contents Prolonged transit time (IBS-C) Exacerbated response to cholecystokinin (IBS-D) Meal ingestion (IBS-D) Visceral Hypersensitivity Heightened sensitivity of the intestines to normal sensation, triggered by bowel distention or bloating Mediated by the local GI nervous system Central modulation from the brain Brain-Gut Axis Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6): Alterations in gut microbiome Bacterial dysbiosis Imbalance of gut microbiota Altered GI motility Increase in GI permeability Immune activation Lee KN, World J Gastroenterol. 2014;20(27): Immune activation Qualitative and quantitative immune cell changes Increase in lymphocytes Seen in post-infectious IBS Mast cells Proinflammatory cytokines Genetics Association with serotonin transporter gene Altered serotonin reuptake efficacy: affects intestinal peristalsis Predisposition to altered pattern of antiinflammatory cytokine interleukin production Mertz H, et al,. Gastroenterology.1995;109(1): Arebi N,et al. Aliment Pharmacol Ther. 2008;28(7):

Psychological Triggers: Anxiety Stress Psychological disease: Depression, Phobias Poor coping skills

Parkes GC, et al., Am J Gastroenterol. 2008;103(6):1557-1567. Fichna J et al., Frontiers Pharmacol.

Diet Increase in intestinal permeability Immune Activation Food specific antibodies Carbohydrate

other conditions Clinical history Physical examination Limited laboratory tests CBC CMP TSH Celiac

6 Psychological Triggers: Anxiety Stress Psychological disease: Depression, Phobias Poor coping skills Psychological Factors: Alters GI motility Visceral hypersensitivity Disruption of brain gut axis Parkes GC, et al., Am J Gastroenterol. 2008;103(6): Fichna J et al., Frontiers Pharmacol. 2012;3:127. Diet Increase in intestinal permeability Immune Activation Food specific antibodies Carbohydrate malabsorption Sorbitol Fructose intolerance Gluten sensitivity Diagnosis based on 4 factors May mimic other conditions Clinical history Physical examination Limited laboratory tests CBC CMP TSH Celiac Serology Stool studies Diarrhea predominant Inflammatory markers Fecal calprotectin Colonoscopy when indicated IBD Celiac Disease Microscopic colitis Lactose/Fructose intolerance No single diagnostic algorithm 6

7 Symptom onset after age 50 years Severe or progressively worsening symptoms Unexplained weight loss Nocturnal diarrhea Family history of organic GI diseases Colon cancer, celiac disease, or IBD Rectal bleeding or melena Unexplained iron-deficiency anemia Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. 2015;313(9): Therapy Dosing Target Symptoms 5-HT3 Antagonist Alosetron mg BID Abdominal pain, diarrhea Considerations Constipation, Rare ischemic colitis Antibiotics Antidepressants Antidiarrheals Antispasmodics Rifaximin 550 mg TID for 14 days May repeat up to 2x TCAs, SSRIs, SNRIs Amitriptyline 10-50mg QHS Loperamide 2-4 mg/d prn Titrate up to 16mg/d Chlordiazepoxide/ Clindinium 5/2.5mg 1-2 caps TID-QID Dicyclomine 10-20mg QD-QID Abdominal pain, diarrhea, bloating Abdominal Pain Diarrhea Abdominal Pain Nausea and increase in ALT Dry eyes and mouth, sedation, constipation or diarrhea Constipation Dry eyes and mouth, sedation, constipation. Caution with use in elderly Mearin F et al Gastroenterolgy

8 Therapy Dosing Target Symptoms Antispasmodics Hyoscyamine mg Q 4 hours PRN Antispasmodics Peppermint Oil: Enteric-coated capsules mg BID-TID Chloride Channel Activators Lubiprostone 8mcg po BID Abdominal pain Abdominal pain Abdominal pain & Constipatio n Diet Low FODMAP, no Gluten Diarrhea, Abdominal bloating Guanylate cyclase C agonist Mixed opioids agonist/ antagonist: Linaclotide 290mcg QD Eluxadoline 100mg BID 75mg BID for those without gallbladder Abdominal Pain & Constipatio n Abdominal Pain & Diarrhea Considerations (see previous page) Constipation, GERD Take with food Difficult to adhere Dry eyes and mouth, sedation, constipation or diarrhea Pancreatitis, SOD spasm Therapy Dosing Target Symptoms Probiotics Psyllium Align 1 daily Florastor 1 BID (Multiple products available) Up to 30g/d in divided doses Psychological/ CBT behavioral therapy Diaphragmatic Breathing Global symptoms, bloating, and gas Diarrhea Global symptoms Considerations Increase in abdominal bloating Dry eyes and mouth, sedation, constipation or diarrhea Tailor treatment to symptoms May need to use a variety of treatments alone or in combination Symptoms may change, therapy will also need to change Mearin F et al. Gastroenterolgy 2016 Mary Davitt PMHNP-BC 8

MDD characterized by persistent feelings of sadness, loss of interest and may include changes in

includes stress that may be out of proportion to the impact of the event.

More anxiety than depression History of abuse/neglect/trauma (sexual abuse in childhood appears to

serotonin levels Dysregulation of the hypothalamic-pituitaryadrenal axis and dysfunction in the

9 MDD characterized by persistent feelings of sadness, loss of interest and may include changes in sleep, appetite, energy, concentration and may be associated with thoughts of suicide Anxiety includes stress that may be out of proportion to the impact of the event. Excessive worry, fear, impending doom, nausea, trembling Chicken or egg? More anxiety than depression History of abuse/neglect/trauma (sexual abuse in childhood appears to be the most significant contributor) Gut as the small brain Alterations in norepinepherine and serotonin levels Dysregulation of the hypothalamic-pituitaryadrenal axis and dysfunction in the brain gut axis is fundamental to the development of IBS Attributable to the development of a maladaptive stress response that occurs through the immune system due to inflammation 9

Build a strong therapeutic rapport Ask questions regarding history of trauma and abuse Comprehensive evaluation of previous

professional Lower quality of life Continued impairment in daily functioning negatively impacting relationships, finances

that psychiatric care actually lowers the cost of IBS treatment A substantial portion of IBS sufferers do not attain

10 Build a strong therapeutic rapport Ask questions regarding history of trauma and abuse Comprehensive evaluation of previous history of mental health/chemical dependency problems Assess psychosocial stressors Enlist the help of mental health professional Lower quality of life Continued impairment in daily functioning negatively impacting relationships, finances and occupational standing Disability and lost wages Worsening emotional distress Substance abuse Suicide Studies demonstrate that psychiatric care actually lowers the cost of IBS treatment A substantial portion of IBS sufferers do not attain adequate relief though conventional medical approaches Improved symptom management (GI) and improved daily functioning Empower your patients 10

Developed by Aaron Beck in the 1960 s Short term, goal oriented psychotherapy Goal is

and feel Identify dysfunctional thinking Develop adaptive/accurate perceptions Most

physical and psychological distress despite reasonable medical investigation Goals:

Rarely available as part of routine care, significant demands on patient s time Lack

classes of psychotropics used with IBS TCA s, SSRI s, SNRI s Potential to modulate

11 Developed by Aaron Beck in the 1960 s Short term, goal oriented psychotherapy Goal is to change patterns of thinking (cognition) in order the change the way people behave and feel Identify dysfunctional thinking Develop adaptive/accurate perceptions Most studied form of therapy (EBP) Most appropriate for patients who have significant physical and psychological distress despite reasonable medical investigation Goals: Reduce GI symptoms and reduce psychological distress Potential drawbacks include: Rarely available as part of routine care, significant demands on patient s time Lack of trained therapists and practical difficulties scheduling weekly visits Three classes of psychotropics used with IBS TCA s, SSRI s, SNRI s Potential to modulate pain perception and treat co-existing psychiatric disorders and possible direct effects of GI motility and secretion 11

12 Imipramine, Amitriptyline, Desipramine, Doxepin Work in the CNS to blunt pain and other symptoms exacerbated by stress in IBS patients Very effective agents but high drop out rates due to adverse effects Serotonin (5-HT) is a key neuromodulator in the control of GI function Triggers peristaltic and secretory reflexes through activation of intrinsic and extrinsic neural pathways Symptoms that appear to respond include abdominal pain and bloating with noted beneficial effects on general well being Tend to be more tolerable Negotiate a treatment plan Educate regarding potential adverse effects Start with a low dose Titrate slowly (every 1-2 weeks) Follow-up (adherence, AE s, efficacy) Refer to Psychiatric provider if needed 12

13 Indications and Benefits Rumination syndrome Urgency/fear of accidental bowel leakage Relieves physical muscle tension Increase 02 to all cells Slows heart rate and lowers blood pressure Increases blood flow to muscles Tried and True CBT TCA s / SSRI s/ SNRI s Diaphragmatic Breathing Promising and New Mindfulness-based stress reduction (MBSR) Exposure-based behavior therapy Rachel Richardson,RD 13

14 Fermentable Oligiosaccharides (Fructans and galactans) Disaccharides (Lactose) Monosaccharides (Excess Fructose) Polyols (sugar alcohols including sorbitol, mannitol, xylitol, isomalt) IBS with persistent symptoms Suggestive for those with dormant Crohn s (more studies need to be done to explore benefits) Ulcerative colitis with functional symptoms End-ileostomy with high output Those who rely on convenience foods due to physical or social circumstances (onion and garlic are difficult to avoid with use of convenience foods). I.E those in nursing homes or are limited to microwave cooking Those with difficulty reading due to need to read food labels and food packages. Those with increased stress associated with following a restrictive diet. 14

15 Fructose is absorbed by 2 pathways in the small intestine High capacity, facilitated transport using the GLUT2 transporter that absorbs fructose in the presence of glucose Low capacity, facultative transport that occurs via GLUT 5 transporter. This pathway is down regulated in some individuals, potentially resulting in malabsorption of fructose. Additional glucose to facilitate absorption via GLUT2 transporter may improve fructose absorption Lactose: Malabsorption is most likely due to lactase enzyme deficiency. Most people can tolerate small amounts of lactose in their diet. Polyols: breath hydrogen test shows 60% malabsorption in healthy individuals GOS and FOS: are malabsorbed by all humans due to deficiency in enzymes to break these down Elimination phase Elimination: remove all sources of FODMAPs from the diet until symptoms resolve Could take 2-8 weeks Challenge Phase Challenge: reintroduce 1 test food every 4 days and monitor tolerance and GI symptoms, if no symptoms this food can be part of the diet Introduce fructans and galactans last Malabsorbed by all humans and the goal is to provide a variety of foods as soon as possible without triggering symptoms 15

16 Breath testing for fructose, lactose, and sorbitol can be done to allow more liberal initiation of the low FODMAP diet. If hydrogen breath test is negative, it is likely not the cause of the symptoms and can be included in the diet. 16

17 IBS is multifactorial: may include stress, emotion, and food triggers Monitor calcium for those following a strict low FODMAP diet for 4 or more weeks, may become deficient The dietitian should provide a variety of low FODMAP calcium options to include in the diet Threshold of FODMAPs is different for all individuals Discontinue Low FODMAP diet if symptoms due not improve after 8 weeks of following the diet; in this case FODMAPS are likely not the cause of the symptoms Low FODMAPs may cause constipation; reintroducing high FODMAP foods to tolerance may help alleviate. Provide a variety of foods that are allowed on the low FODMAP diet to prevent nutrition deficiencies Help with initiation of the low FODMAP diet to alleviate stress of eating and changes in the diet Provide safe go-to foods to ease the transition to a low FODMAP diet Provide tips for relaxing environment during a meal due to association of stress and IBS flareups. (Psychologist may be able to help with this) 17

18 Provide education and reassurance Tailor treatment plans based on disease characteristics Early and effective communication Address the psychological component Nonpharmacologic management options Diet modification Behavioral interventions Nonprescription medications Thank you! Medline S. The low FODMAP diet: New hope for IBS sufferers. Gastrointestinal Nursing (9). Barrett JS., Gibson PR. FODMAPS and nonallergic food intolerance: FODMAPs or food chemicals? Therapeutic Advances in Gastroenterology (4). Shepard SJ., Halmose E., Glance S. The roles of FODMAP in IBS. Functional foods and dietary supplements (6) Riggs S. The low FODMAP Diet: An approach for controlling IBS. Topics in Clinical Nutrition (4) Staudacher HM., Whelan K., Irving PM., Lomer CE. Comparison of symptom response following advice for a diet low in FODMAP versus standard dietary advice in patients with IBS. The Journal of Human Nutrition and Dietetics Barrett JS. Extending our knowledge of FODMAP for managing GI symptoms. Nutrition in Clinical Practice (3) 18

Irritable Bowel Syndrome Now. George M. Logan, MD Friday, May 5, :35 4:05 PM

Irritable Bowel Syndrome Now. George M. Logan, MD Friday, May 5, :35 4:05 PM Irritable Bowel Syndrome Now George M. Logan, MD Friday, May 5, 2017 3:35 4:05 PM Dr. Logan indicated no potential conflict of interest to this presentation. He does not intend to discuss any unapproved/investigative