New Perspective in Irritable Bowel Syndrome

Anthony Lembo, M.D.Professor of Medicine

Harvard Medical School

Director, GI Motility and FBD Center

Beth Israel Deaconess Medical Center

Boston, MA

COPYRIGHT

Early description of Symptoms Defining IBS

• IBS: Chronic abdominal pain associated with altered bowel habits (diarrhea/constipation/mixed)

• Symptoms are not new

• “The bowels are at one time constipated, at another lax, in the same person.

How the disease has two such different symptoms I do not profess to explain. . . .” W Cumming, 1849

•Historical terms– mucous colitis – colonic spasm – neurogenic mucous colitis – irritable colon

W. Cumming, London Medical Gazette, 1849;NS9;969-973.

– unstable colon– nervous colon– nervous colitis– spastic colitis

•

COPYRIGHT

E3

IBS Prevalence According To Age, Geography and Sex

0 10 20 30 40 50 60 70 800

10

20

30

Age (years)

Hungin APS et al. APT 2005; 21:1365

Hungin APS et al. APT 2003; 17:643

Kumano H et al. AJG 2004; 99:370

Lau EMC et al. Dig Dis Sci 2002; 47:621

%

Rome

IBS W. Europe

USA

Japan

China

1.2-2 x Women : Men

(particularly IBS-C)

COPYRIGHT

Prevalence IBS in Japan

• Rome II: 6.1% - 14.2% (4.5% - 12.9% men;

7.8% - 15.5.% women) • Kamazawa et al. 2004, Kumano et al. 2004

• Rome III: 13.1%

• 15.5% women; 10.7% men

• IBS-D 29%, IBS-C 24%, IBS-M 47%

• Miwa et al. 2008

E4

COPYRIGHT

~25%

Consulters

~75%

Nonconsulters

Pain/Severity

Concern for

malignancy/IBD

Psychological

disturbance

Consulters vs. Non-consulters

IBS Non-consulters and Healthy Controls have Similar Psychosocial Profiles

IBS patients have higher rates of psychosocial abnormalities

(anxiety/depression)

COPYRIGHT

Most Bothersome Symptoms of IBS

Ballou S. t al. Clin Gastroenterol Hepatol. 2019 Aug 13. [Epub ahead of print]

Impact of Symptoms

Data from IBS in America Survey n=1885

COPYRIGHT

Lacy B et al. Gastroenterology. 2016;150:1393-1407 Rome Organization. Rome IV Disorders and Criteria.

Rome IV Criteria for IBS

*Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

Associated

with a change

in frequency of stool

Associated

with a change in

form/appearance

of stool

Recurrent abdominal pain

at least 1 day / week in the last 3 months

associated with 2 or more of the following:

Related to

defecationCOPYRIGHT

IBS Subtypes Based on Stool ConsistencyBased on Days With Abnormal BMs

Type 1

Separate hard lumps, like nuts (hard to pass)

Type 2

Sausage-shaped but lumpy

IBS-ConstipationHard/lumpy stools ≥25%

Loose/watery stools <25%

Type 3

Like a sausage but with cracks on its surface

Type 4

Like a sausage or snake, smooth and soft

Type 5

Soft blobs with clear-cut edges (passed easily)

IBS-MixedHard/lumpy stools ≥25%

Loose/watery stools ≥25%

Type 6

Fluffy pieces with ragged edges; a mushy stool

Type 7

Watery, no solid pieces; entirely liquid

IBS-DiarrheaHard/lumpy stools <25%

Loose/watery stools ≥25%

Lacy BE et al, Bowel Disorders, 1393-1407.e5, r.

Bristol Stool Form Scale1,2

8

COPYRIGHT

E9Turn Down the Pain Volume. The Rheumatologist October 2009 • Daniel J. Clauw,

IBS Overlaps with other Common Chronic Pain Conditions

COPYRIGHT

19701960 1980 1990 2000 2010 20141950 2019

MotilityMyoelectrical Marker

Brain-Gut Interactions

Visceral Hypersensitivity

Mechanisms

Inflammation

Microflora

Food and Diet

Mucosal Immune Dysfunction

Stress affects GI function

Meals

Pain/Motility

Pain sensitivity

3 cpm

motility

Clusteredcontractions

CNS/ENSAutonomic reactivity

Visceralhypersensitivity

Postinfection

IBS

CNSBrain Imaging

Probiotics

Food and Diet

FODMAP

Gluten

Neuroplasticity and Neurogenetics

Biomarkers

EpigenomicsRome Criteria

IBS - Physiologic Research

COPYRIGHT

What Causes IBS Symptoms?

Genes

Early learning

Family influences

Susceptible

individual

External stressors

IBS symptoms

Psychological

disturbance

Physiological

disturbance

• Stressful adverse life events

• Chronic psychological stress

• Gastrointestinal infection

• Alterations in gut microbiota

• Changes in diet

Courtesy of Robin Spiller

COPYRIGHT

IBS is Common After an Infectious GastroenteritisPost-infectious IBS (PI-IBS)

• IBS is present in 10% of individuals

12 months after an infection

• Parasitic > Bacterial > Viral

• Risk of IBS > in women, antibiotic

use, anxiety, depression,

somatiziation neuroticism

• Gastroenteritis affects 15% of US

population /year

• Post-infectious IBS is the leading

cause of IBSMarshall et al. Gut 2010 May;59(5):605-11.

Flem et al.. Gastroenterology. 2017 April ; 152(5): 1042–1054

PI-IBS Walkerton, Ontario

10 year f/u

COPYRIGHT

Post-Infectious IBS is Associated with Increased Immune Cells and Hypersensitivity

0

50

100

150

200

Discomf Inflamm Psych

IBS + IBS - Control

*

* *

Gwee, Gut, 1999;44:400.

Control

Post infectious IBS

Spiller, Gut, 2000; 47(6): 807.

Increased

Enterochromaffin Cells

Visceral Hypersensitivity

Chronic lymphocytes at f/u

Intestinal permeability

COPYRIGHT

Evidence for Increased Intestinal Permeability in IBS (i.e., Leaky Gut)

• 1st described in IBS in 2000 (post-infectious) (Spiller et al)

• Has since been demonstrated in all subtypes of IBS

• Fecal supernatant from IBS patients increases colonic permeability in mice

• Permeability decreases with GFD and low-FODMAP diet

• Glutamine 5 g tid x 8 wks improved IBS symptoms and permeability (Zhou et al. Gut 2018)

Singh P, et al. United European Gastroenterology Journal 2019, Vol. 7(5) 709–715

COPYRIGHT

Proposed Mechanism of Post-infectious IBS

E15IBSSmart.com

COPYRIGHT

Anti-CdtB and vinculin antibodies are common in IBS-D

Potential Biomarker for Post-infectious IBS-DAnti-CdtB and anti-vinculin antibodies are elevated in IBS-D compared with IBD, UC,

and celiac disease

E16Pimentel et al. PLOS One 2015

Morales W, et al. Digestive Diseases and Sciences. Published on-line May 2019

IBS-D IBS-D

COPYRIGHT

Diagnosing IBS in the ClinicHistory and Physical Exam

• History

• Typical Symptoms (Rome)

• Timeline and triggers

• Alarm features• FH IBD/Colon Ca/celiac; weight loss; anemia, blood in

stools, nocturnal awakening, onset > 50 yr age

• Travel to areas with high prevalence of infectious

diarrhea, immunosuppression

• Other functional disorders

• Diet

• Medications (including OTC)

• Psychosocial factors (stress,

anxiety, etc.)

• Physical Exam

• Signs of systemic and

local diseases

• Digital rectal exam to

assess for dyssynergia

(especially in patients with

constipation)

Lembo and Camilleri, Chronic Constipation, N Engl J Med 2003;349:1360-1368

COPYRIGHT

• CRP or fecal calprotectin

• IgA TtG ± quantitative IgA

• Stool diary

• Consider abdominal plain film to

assess for fecal loading

If severe or medically refractory,

refer to specialist for

physiologic testing

Diagnostic Testing for Patients with Suspected IBS

*1. Chey WD, et al. JAMA. 2015;313(9):949-958.

• Strong Recommendation

• Test for giardia

• IgA TtG ± quantitative IgA

• Conditional Recommendation to use

• fecal calprotectin or lactoferrin

• Test for bile acid (serum C4)

• Conditional recommendation against

• Stool for O&P in absence of relevant

travel

• ESR or CRP (except if stool tests are

not available

IBS-D2 IBS-M1 IBS-C1

CBC

Age-appropriate CRC screening

2. Gastroenterology 2019 Sept. 157(3): 851

COPYRIGHT

Diagnostic Testing for Patients with Suspected IBS

• When to consider a colonoscopy?

• Alarm features

• Age appropriate screening

• Persistent frequent watery diarrhea

• Obtain bx to r/o microscopic colitis

• Failure to respond to therapy

• Breath Testing?

• Insufficient data to recommend

• May predict response to rifaximin• 60% response if positive BT vs. 26% negative BT

Rezaie, Ali MD, MSc American Journal of Gastroenterology 112:S227 (abstract), October 2017

COPYRIGHT

0

10

20

30

40

50

60

0 2 4 6 8 10 12 14 16

Placebo in Clinical Trials

Week

%

with relief“Placebo” arm

Treatment period Follow-up period

Drug arm

Therapeutic gain

Natural history of disease

Spontaneousremission,Regression tothemean+

“Placebo Effect”

“HawthorneEffect”,Co-interventions,expectation,

reportbias,measurements

Patient-practitionereffect

Key Assumption: Placebo + Treatment Effects are Additive

COPYRIGHT

•Elsenbruch and Enck. Nature Reviews Gastroenterology &Hepatology 2015

.

Factors Associated with Response to Placebo in IBS trials

• Number of office visits

• Frequency of interventions (i.e., pills)

• Greater pain variability during baseline and

higher pain rating during baselineBallou S et al. Clinical Gastroenterology and Hepatology 2018 16, 1738-1744

• Age and sex are not predictors

• ? Duration of study/run-in, location of study

COPYRIGHT

•6weeks

•PatientswithIBSwererandomizedto:•Augmented clinician patientrelationship+sham

acupuncture

•Limited clinician patientrelationship +shamacupuncture

•Waitlist

•AugmentedclinicianpatientRelationship

included:

•Warm,empathetic,andconfident

•Activelistening

•20secofthoughtfulsilence

•Physicalcontact– feltpulse

•Increasedtime(30minover3weeks)

Components of the Placebo Effect:A RCT in Patients with IBS

COPYRIGHT

Hall,Lemboetal. PLoS ONE 7(10): 2012

More dopamine

epinephrine,

norepinephrine)

SAH

COMT

Dopamine

Nor-

epinephrine

Epinephrine

Catechol

estrogen

SAM

COMTmetabolizescatecholamines

Less dopamine

epinephrine,

norepinephrine

COPYRIGHT

COPYRIGHT

A

3

4

5

6

No Treatment Open Placebo

Glo

bal I

mpr

ovem

ent (

IBS-

GIS

)

B

0

20

40

60

80

100

120

No Treatment Open Placebo

Sym

ptom

Sev

erity

Cha

nge (

IBS-

SSS)

C

0

10

20

30

40

50

60

70

80

No Treatment Open Placebo

Perc

ent w

ith A

dequ

ate R

elief

(IBS

-AR

)

D

0

5

10

15

No Treatment Open Placebo

Qua

lity

of L

ife C

hang

e (IB

S-Q

OL)

p=.002 p=.03

p=.03 p=.08

Open-labelPlacebo(n=43)

NoTreatment(n=37)

Kaptchuk et al. PLOS ONE 5(12): Dec 2010

Adequate Relief

IBS-SSSGlobal Improvement

IBS-QOLCOPYRIGHT

Graded Treatment Response

• Diet, lifestyle advice• Positive diagnosis

• Explain, reassure

• Psychological treatments• Continuing care

• Central neuromodulators

Severe

Moderate

Mild

+

+

• Follow-up visit• Manage stress

• Gut pharmacotherapy

Rome IV Functional Gastrointestinal Disorders. 4th ed. Raleigh, NC: The Rome Foundation; 2016.

A Therapeutic Clinician-patient Relationship is the Cornerstone of Treatment

COPYRIGHT

Factors Associated with Normal Bowel HabitsData from US General Population (NHANES)

E27Mitsuhashi et al American Journal of Gastroenterology. 113(1):115–123, JANUARY 2018.

95% US population

has between 3 BM/day and 3 BM/wk

COPYRIGHT

General Dietary and Lifestyle Considerations

• ‘Moderate-to-vigorous’ exercise at least activity 3-5 x /week

• Fluid Intake

• Fiber

• Adequate sleep

• Diet

1. Böhn L1,, Gastroenterology. 2015Nov;149(6):1399-1407.e2.2. Ballou S DigDisSci. 2018Nov;63(11):2983-2991.

“Traditional IBS diet”Eat 3 meals and <3 snacks a day: do not over eat!

Reduce fatty or spicy foods, coffee, alcohol, onions, cabbage and beans

Avoid soft drinks, chewing gum, sweeteners that ends in –ol

Consider increasing soluble fibers - take evenly during the day

Low-FODMAPFermentable oligo-di-mono saccharides and Polyols

? Gluten Free, Paleo, Elemental, South Beach ???

COPYRIGHT

Fiber

• Lowers risk of CV disease and diabetes, and all-cause mortality

• Important characteristics:

• Solubility, fermentability, viscosity, gel formation

• Food is the best source of fiber!

• whole-grain products, fruit, vegetables, beans, peas/legumes, and nuts /seeds

• ‘Good source of fiber’: > 2.5 grams per serving , ‘High fiber’: >5 grams per serving

• Recommended amounts: 25 g/d women, 38 g/d men

• Psyllium is the most studied fiber supplement in IBS

E29

COPYRIGHT

Proportion of Patients with Adequate Relief of Symptoms*

Psyllium 10 g per day Improves IBS SymptomsP

ati

en

ts, %

RR-1.66

(95% CI: 1.19-2.3)

Placebo (n=93) B Bran 10 g (n=97) Psyllium 10 g (n=85)

Month 1 Month 2 Month 3

RR-1.44

(95% CI: 1.04-2.0)

Early dropout more common in the bran group. Bijkerk CJ et al. BMJ. 2009;339:b3154.

N=275 IBS patients followed in Primary Care

10 g per day

10 g per day

COPYRIGHT

Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs)

Excess

FructoseLactose Fructans Galactans Polyols

fruit

apple, mango, pear,

cherries,

watermelon

sweeteners

sugar, high-fructose

corn syrup

other

honey, asparagus

milk

milk from cows,

goats, or sheep;

custard, ice cream,

yogurt

cheeses

soft unripened

cheeses

(eg, cottage

cheese,

ricotta)

vegetables

onion, leek, garlic,

shallots, artichokes,

asparagus, peas,

beetroot, chicory

cereals

wheat, barley, rye

legumes

baked beans,

chickpeas, kidney

beans, lentils

fruit

apple, pear, apricot,

cherries, peaches,

nectarines, plums,

watermelon

vegetables

cauliflower,

mushrooms

sweeteners

sorbitol, mannitol,

xylitol, chewing gum

1. Shepherd SJ, et al. Am J Gastroenterol. 2013;108:707-717.

2. Shepherd SJ, Gibson PR. J Am Diet Assoc. 2006;106:1631-1639. 3. Barrett JS, Gibson PR. Ther Adv Gastroenterol. 2012;5:261-268.

31

COPYRIGHT

Low-FODMAP Diet

E32

COPYRIGHT

Efficacy of Low-FODMAP Diet in IBS

Halmos EP, et al. Gastroenterology. 2014;146:67-75.

VA

S (

0-1

00

mm

)

Day

Typical Australian diet

Low-FODMAP diet

60

40

20

P<.001

Böhn L, et al. Gastroenterology. 2015. doi: 10.1053/j.gastro.2015.07.054.

Low-FODMAP vs.

Typical Australian Diet

Low-FODMAP vs.

“Traditional IBS Diet”

COPYRIGHT

Fructans and Not Gluten Induces Symptoms in Non-celiac Gluten Sensitivity and IBS

Murray et al. Am J Gastroenterol 2014 Jan;109(1):110-9

Common fructans

Wheat including bread, pasta, etc.,

onions,, garlic, barley, brussels sprouts,

cabbage, broccoli,, artichoke, inulin

Skodje et al. Gastroenterology 2018;154:529–539

Fructan distends the colon with gas

Fructose distends the small bowel with waterCOPYRIGHT

Frischer-Ravens et al. Gastroenterology 2019;157:109–118

Confocal Light Endoscopy (CLE) positive rates: wheat (60%), yeast(20%),

milk(9%), soy(6%), egg(4%)

COPYRIGHT

Severe

Moderate

Mild

+

+

● Psychological treatments

● Continuing care

● Improve functioning

● Follow-up visit

● Manage stress

● Pharmacotherapy

● Diet, lifestyle, advice

● Positive diagnosis

● Explain, reassure

Graded Treatment of IBS

90

COPYRIGHT

Many Treatments Options for IBS

Bloating/ distension

Altered bowel

function

Abdominal pain

PEG, polyethylene glycol; SNRI, serotonin and norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant

DiarrheaAntispasmodics

Loperamide

TCA

Rifaximin**

Eluxadoline**

Alosetron**

Ondansetron

Bile Acid Binder

ConstipationPsyllium

Osmotic laxatives (PEG)

Lubiprostone*

Linaclotide*

Plecanatide*

Biofeedback (dyssynergia)

Diet (eg, FODMAP)

Probiotics

Rifaximin**

Antispasmodics

SNRI/TCA

Rifaximin**

Eluxadoline **

Alosetron**

Lubiprostone*

Linaclotide*

Plecanatide*

FDA approved for IBS-C* /IBS-D**

COPYRIGHT

First Line Treatment for IBS

• Constipation

• Fiber (soluble): 5 g QD – increase if tolerated to 10 g

• Polyethylene glycol: 17 g QD, titrate until stools are soft but formed

• Diarrhea

• Loperamide: 1 tablet qAM or BID, increase if stools remain loose

• Bile acid sequestrant (e.g., colestipol)

• Pain

• Antispasmodic: hyoscyamine, dicyclomine, peppermint oil

• Tricylic antidepressant: nortryptyline/desipramine 10 mg Qhs, increase

up to 50 mg Qhs

• Bloating

• Probiotic (bifidobacter infantis, combination probiotics, etc. )

Ford A, Lacy B, Talley N. N Engl J Med 2017; 376:2566-257

COPYRIGHT

Polyethylene Glycol (PEG) Improves Bowel But Not Abdominal Symptoms in IBS-C

Chapman RW, et al. Am J Gastroenterol. 2013;108(9):1508-1515.

Spontaneous Complete

Bowel Movements (SCBMs)Abdominal Discomfort/Pain

*P<.0001.

N=68 N=71

• Between 1 and 3 sachets of PEG 3350 + E (13.8 g per day) or matching placebo

were administered

• Patients adjusted the dose based on stool consistency

39

COPYRIGHT

Mechanism of Action:Secretogogues for IBS-C

Tack J, Gastroenterology 2018;155:1677–1691

COPYRIGHT

FDA Endpoint Responder rates

>30% improvement in abdominal pain + >1CSBM /wk

Efficacy of Secretogogues in IBS-CSystematic Review and Network Meta-analysis

Black CJ et al. Gastroenterology2018 Dec;155(6):1753-1763.

“Efficacy was similar among individual drugs and dosages for most end points.”

COPYRIGHT

Tenapanor 50 mg BID Improves IBS-C Symptoms

• Tenapanor is a minimally absorbed sodium/hydrogen exchanger isoform 3 inhibitor (NHE3)

• Phase III Clinical Trial (12 weeks; 4 week randomized withdrawal)

• FDA Approved for IBS-C (Sept. 2019)

Chey W, Lembo A, Rosenbaum D al. AJG in press 2019

6/12 week responders

9/12 week responders

FDA Responder

>30% abdominal pain +

>1 CSBM /wkCOPYRIGHT

Tegaserod, 5-HT4 partial agonist, Improves IBS-C Symptoms

• FDA reapproved (Sept.

2019) 6 mg BID for women

< 65 years

• Contraindicated in

patients with h/o MI,

stroke ,TIAs, or angina, or

ischemic colitis, ESRD,

hepatic impairment (Child-

Pugh B or C)

Chey W, Am J Gastroenterol 2008;103:1217–1225

COPYRIGHT

Mechanism of Action: IBS-D Treatments

Opioid receptor modulatorsLoperamide (mu agonist)

Eluxadoline * (mu-agonist, delta-antagonist

Modulation of gut floraRifaximin *

Probiotics

Neuromodulators TCAs/SNRIs

Pre-gabalin

5-HT3 antagonistsAlosetron *

Ondansetron

Bile acid binding agentsCholestyramine

Colestid/Colesevelam

Antispasmodics

Anti-cholinergics

Peppermint oil

*FDA-approved for management of IBS-D.

COPYRIGHT

”We found all drugs to be superior to placebo, but alosetron and ramosetron

appeared to be the most effective.”

Black CJ et al. Gut 2019 Apr 17. pii: gutjnl-2018-318160

Efficacy of IBS-D TreatmentSystematic Review and Network Meta-analysis

COPYRIGHT

Phase III Clinical Trials: Eluxadoline for IBS-D

FDA Responder

≥30% improvement of abdominal pain and stool consistency score of BSS type <5 for ≥50% of daysR

esp

on

ders

, %

Δ 9.5†

Δ 10.3†

Δ 7.2†

Δ 11.5†

Wk 1–12 Wk 1–26

35

30

25

20

15

10

5

0

n=808 n=806 n=809 n=808 n=806 n=809

16.7 26.2 27.0 19.5 26.7 31.0

PBO

75mg ELX

100mg ELX

†P<.001

Lembo A et al. N Engl J Med. 2016;374(3):242-253

Lembo A, et al. N Engl J Med. 2016; 374: 242-53

COPYRIGHT

Eluxadoline

• Constipation: 7-8%.

• Pancreatitis in 0.3% (5/1457)

• Sphincter of Oddi Dysfunction in 0.5% (8/1457)

• All cases of pancreatitis/SOD occurred in patients

without a gallbladder or increased ETOH use

• Eluxadoline is contraindicated in patients without a gallbladder (cholecystectomy) or

> 3 alcohol drinks/day;

471. Viberzi (eluxadoline) [prescribing information]. Allergan USA, Inc. Irvine, CA; 2019; 2. Cash B, et al. Am J Gastroenterol. 2017; 112: 365-374.

COPYRIGHT

• Black-box warning: serious GI effects

• Ischemic olitis

• 2 per 1000 pts over 3 months

• 3 per 1000 pts over 6 months

• Constipation

• Alosetron (1 mg bid) = 29%

• Placebo = 6%

• Prescribing Program

• 0.5 mg BID, increase 1 mg BID if

tolerated

Alosetron [package insert]; 2016

*P<0.02vsplacebo

Assessmentat12weeks

GIS=Global ImprovementScale

Safety Profile of Alosetron

Krause R et al. Am J Gastroenterol 2007; 102:1709

Alosetron, a 5-HT3 antagonist, Improves Global Symptoms in Women with Severe IBS-D

COPYRIGHT

Ondansetron* for IBS-DData From a Single Center Study

Garsed K, et al. Gut. 2014;63:1617-25.

**Randomized, double-blind, dose-titration study. Primary endpoint was

average stool consistency in last 2 weeks of treatment. Improvements in

urgency, frequency, bloating but NOT pain.

*Off-label

Bri

sto

l S

tool

Form

Score

Effect of Ondansetron 4 to 8 mg TID for 5 Weeks

in Patients With Rome III IBS-D (N = 120)**

Treatment 1 Treatment 2Washout

Endpoint Weeks Endpoint Weeks

Crossover

4

6

5

3

2

1

Ondansetron

Placebo

7

COPYRIGHT

GI Society Guidelines for IBS Treatment

Medication Society Recommend

ation

Quality of

Evidence

Comments

Antispasmodi

cs

AGA1,2 Conditional Low Low cost, wide availability, minimal adverse

effects

ACG3 Weak Very low

Low*

Adverse events were dry mouth, dizziness,

and blurred vision

Tricyclics AGA1,2 Conditional Low Used with caution in pts with prolonged QT

ACG3 Strong High Effective in relieving pain and overall sxs,

Limited by patient acceptance and side effects

SSRIs AGA1,2 Conditional

against

Low No improvement in abdominal pain

ACG3 Weak Low Effective in relieving pain and overall sxs,

Limited by patient acceptance and side effects

Diet ACG3 Weak Very low Low FODMAP and gluten free or exclusion

diet based on antibody or leukocyte activation

test for overall sx improvement

Probiotics ACG3 Weak Low Improve global sx, bloating, flatulence

Psychological ACG3 Weak Very low Overall sx improvement; some have absence

of true sham control, may be therapist

dependent

COPYRIGHT

Neuromodulator for IBS and FBDs

SSRIs TCAs SNRIs

Consider when anxiety, depression, and phobic features are prominent with

FGIDs

Treatment when pain is dominant in FGIDs or when side effects from TCAs preclude

treatment

First-line treatment when pain is

dominant in FGIDs

Tetracyclic antidepressan

t

Treatment of early satiety, N/V, weight loss and disturbed

sleep

(paroxetine, fluoxetine, sertraline, citalopram,

escitalopram)

(amitriptyline, nortriptyline, imipramine,

desipramine)

(duloxetine,venlafaxine,

desvenlafaxin, milnacipran)

(mirtazapine, mianserin, trazodone)

Drossman DA et al. Gastroenterology 2018;154:1140–1171

COPYRIGHT

Standard CBT (s-CBT) (n=146)

10 wkly sessions

Minimal Contact (MC-CBT) (n=145)

4 session of home based CBT

Education control (n=145)

4 sessions education

Cognitive Behavioral Therapy for IBS

Lackner J, Gastroenterology. 2018 Jul; 155(1): 47–57.

Global Improvement at week 12

COPYRIGHT

First Line Treatment for IBS

• Constipation

• Fiber (soluble): 5 g QD – increase if tolerated to 10 g

• Polyethylene glycol: 17 g QD, titrate until stools are soft but formed

• Diarrhea

• Loperamide: 1 tablet qAM or BID, increase if stools remain loose

• Bile acid sequestrant (e.g., colestipol)

• Pain

• Antispasmodic: hyoscyamine, dicyclomine, peppermint oil

• Tricylic antidepressant: nortryptyline/desipramine 10 mg Qhs, increase

up to 50 mg Qhs

• Bloating

• Probiotic (bifidobacter infantis, combination probiotics, etc. )

Ford A, Lacy B, Talley N. N Engl J Med 2017; 376:2566-257

COPYRIGHT

Summary of RCTs of FMT in IBS

• Recent meta-analysis: no difference between placebo and

FMT (51% vs. 49% response rate; 4 trials; n = 254)

• NJ or colonoscopic administration > greater efficacy

• Abstract presented at UEG week 2019

• Super donor with ‘favourable fecal microbial profile (Norway)

• 164 IBS moderate/severe symptoms (IBS-SSS score < 175

• Proximal duodenum via gastroscope

• Clinically significant improvement: 5.5% placebo vs. 35.2% FMT

30g vs. 47.3% FMT 45g

Xu et al, Am J Gastroenterol 2019; El-Salhy et al. UEG week 2019

COPYRIGHT

Conclusions• IBS is a chronic pain condition due to disregulation in brain-

gut axis

• Cornerstone of treatment include a therapeutic clinician patient relationship, dietary modifications, increase exercise and stress reduction

• First line treatment is based on predominant symptom• IBS-C: PEG + fiber

• IBS-D: loperamide

• Pain: Anti-spasmodics or TCA

• Other treatments including prescription medications and psychological therapies are available for persistent symptoms

COPYRIGHT

Thank You

COPYRIGHT