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IBS-C and IBS-D:Tailoring Non-pharmacologic and Pharmacologic Interventions

Gregory Sayuk, MD, MPHAssociate Professor of Medicine and PsychiatryWashington University in St Louis

Disclosures• The following are my disclosures. Potential conflicts

of interest have been resolved.

Research Support / Grants None

Stock/Equity None

Consulting Synergy, Allergan/Ironwood

Speakers Bureau / Honoraria Synergy,Allergan/Ironwood, Salix

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IBS Direct and Indirect CostsHigh economic and social burdens

– Direct costs: medications, testing• Up to 30 million adults affected in U.S.• 1.5 x more office visits (25% GI of practice)

– Indirect costs• Miss work/school (avg 2.4 days/month)• 13.7 million days lost productivity/year• 60% report impairment at work due to symptoms

Dennison C et al.Pharmacoeconomics 2005. Bracco K et al. Am J Gastroenterol 2004. Agarwal N and Spiegel BMR. Gastroenterol Clin NA 2011. Chang L et al. AP&T 2004. Whitehead WE et al. J Am Geriat Soc 1989. Talley NJ. Rev Gastroenterol Disord 2004. Spiegel B et al. AP&T 2007.

– Lower health-related QOL– Psychological impact

• Higher depression/anxiety• Suicidality?

– More restricted physical/social activities

Recurrent abdominal pain, on average, ≥1 day per week in

the last 3 months, associated with ≥ 2 of the following:

• Related to defecation• Change in frequency of

stool

• Change in form(appearance) of stool

Defining and Characterizing IBS

Rome IV Criteria for IBS1IBS Subtypes Based on

Bristol Stool Forms2,3

Criteria should be fulfilled for the last 3 months with symptom

onset ≥ 6 months before diagnosis

IBS-C, irritable bowel syndrome with constipation; IBS-D, irritable bowel syndrome with diarrheal IBS-M, irritable bowel syndrome with mixed symptoms.1. Lacy BE et al. Gastroenterology. 2016;150:1393-1407; 2. Longstreth GF et al. Gastroenterology. 2006;130:1480-1491;3. O�Donnell LJD et al. BMJ. 1990;300:439-440.

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Conceptual Biopsychosocial Model of IBSInteraction of factors raise potential for multiple, diverse treatment options

Adapted from: Tornblom H and Drossman D. NGM 2015. See also: Perera TD et al Neuroscientist 2008 and Perera TD et al. J Neurosci 2007.

IBS SYMPTOMS

High

Low

PREDISPOSING FACTORS

Genetics Early trauma

Abuse

Environmental factors

MECHANISTIC FACTORS PERPETUATING FACTORS TREATMENT

Infection

SecretionGut Motility

Visceral hypersensitivity

Diet

Central hypersensitivity*

Diet/lifestyle

Anxiety/stress

Depression

Gut-centric therapy

Antibiotics/probiotics

Antidepressants/psychological

Exercise/yoga

Supportive

Bacterial overgrowth

* Co-morbid pain diagnoses are an important marker

Diet

IBS Treatment An evidence-based approach

Ford AC et al. Am J Gastroenterol 2018.

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IBS-C ManagementPharmacological options

STR

EN

GTH

OF

EV

IDE

NC

E

Hig

hLo

w

Ford AC, et al. ACG Monograph on Management of IBS. Am J Gastroenterol 2018. Weinberg DS et al. AGAI Guideline on Pharmacologic Management of IBS, Gastroenterol 2013.

Lubiprostone

Linaclotide

Antispasmodics/anticholinergics

RECOMMENDATION

Strong Weak

SSRI Antidepressants

Tricyclic antidepressants (TCAs)

Plecanatide

Polyethylene glycol (PEG)

IBS-D ManagementPharmacological options

ST

RE

NG

TH

OF

E

VID

EN

CE

Hig

hL

ow

Ford AC, et al. ACG Monograph on Management of IBS. Am J Gastroenterol 2018.

Loperamide

Antispasmodics/anticholinergics

RECOMMENDATION

Strong Weak

SSRI Antidepressants

Tricyclic antidepressants (TCAs)

Eluxadoline

Alosetron*

5-aminosalicylates

Rifaximin

* Available under FDA Risk Evaluation and Mitigation Strategy (REMS) Drug Safety Prog

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IBS PharmacotherapyRegulatory agencies mandate improvements in both

abdominal pain and bowel pattern

Linaclotide Linaclotide Linaclotide Linaclotide

Chey WD et al. Am J Gastroenterol 2012.Rao S et al. Am J Gastroenterol 2012.

Linaclotide in IBS-C Abdominal pain continues to improve over 26 weeks

P=.007 for Week 1P<.0001 for Weeks 2-26

Chan

ge in

Abd

omin

al P

ain

(%)

-60

-50

-40

-30

-20

-10

0

Trial WeekBL 2 4 6 8 10 12 14 16 18 20 22 24 26

Linaclotide 290 mcg Placebo

Chey WD et al. Am J Gastroenterol 2012.

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Antidepressants for Somatic Pain SyndromesMultiple controlled trials demonstrate benefit

1

O'Malley PG, et al. J Fam Pract. 1999;48:980-990.

Chronic Fatigue

Fibromyalgia

Functional GI

Idiopathic Pain

Headache

Tinnitus3.4 (2.6-4.3)

Odds ratio

Treatment Worse Treatment Better

AntidepressantsPutative effects on abdominal pain

• Central effects– Alterations in pain

perception (analgesia, antihyperalgesia)

– Modified attention to pain– Decreased stress

responses– Improvement of mood,

psychiatric disorders– Treatment of sleep

disturbances

• Peripheral effects– Alterations in visceral

afferent signaling– Effects on GI physiology

• Smooth muscle relaxation• Decreased secretion

Grover M and Drossman DA. Gastroenterol Clin N Am 2011.

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Meta-analysis: TCAs in IBS

Studyor sub-category

Treatmentn/N

Controln/N

RR (random)95% CI

Weight%

RR (random)95% CI

Tricyclic antidepressants

Heefner 1978Myren 1982Nigam 1984

Boerner 1988Bergmann 1991

Vij 1991Drossman 2003

Talley 2008Vahedi 2008

10/225/30

14/2116/425/19

14/2560/115

0/188/27

12/2210/3121/2119/4114/1620/2536/575/16

16/27

Subtotal (95% CI) 319 256 67.56 0.68 (0.56 to 0.83)

5.942.66

14.747.633.82

10.6716.770.335.02

0.83 (0.46 to 1.51)0.52 (0.20 to 1.33)0.67 (0.49 to 0.90)0.82 (0.50 to 1.36)0.30 (0.14 to 0.65)0.70 (0.47 to 1.04)0.83 (0.63 to 1.08)0.08 (0.00 to 1.36)0.50 (0.26 to 0.97)

Total events: 132 (treatment), 153 (control) Test for heterogeneity: X2 = 10.92, df=8, (P=.21), I2 = 26.9%

Test for overall effect: Z=3.86 (P=.0001)

Ford AC et al. Gut 2009 Mar;58(3):367-78.Ford AC et al. Am J Gastroenterol 2014.

Number needed-to-treat (NNT) using TCAs in IBS = 4

Higher doses (>50 mg) may be more effective in IBS-D

1. Ford AC et al. AJG 2014. 2. Lesbros-Pankoflickova et al. Aliment Pharmacol Ther 2004.

Side-effects from TCA treatment of FGIDs are common

0

10

20

30

40

50

% o

f sub

ject

s

Irritable bowelsyndrome

Functionaldyspepsia

SedationOther CNSAnticholinergic

Clouse RE et al. Dig Dis Sci 1994; Prakash C et al. Dig Dis Sci 1998.

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Tricyclic AntidepressantsReceptor affinity predicts side effects

Receptor Affinities*

* For acetylcholine, histamine, and a-adrenergic receptors

3o

amines Amitriptyline Imipramine Doxepin ++ - +++

Nortriptyline Desipramine2o

amines + - ++

Clouse RE and Lustman PJ. GUT 2006.

Recent Tricyclic Antidepressant Trials for IBS

Rajagopalan1998 Amitriptyline (25à75)

12-wk DB RCT

n=40+ + +

Drossman 2003 Desipramine(50à150)

12-wk MC CC RCT

n=216- NA +*

Morgan 2005 Amitriptyline (50) 4-wk RCT

n=19 + NA NA

Vahedi 2008 Amitriptyline (10) 8-wk DB RCT

n=50- + +

Bahar 2008 Amitriptyline (10-30) 13-wk DB RCT

n=33 (adolescent)+ - +

Abdul-Baki 2009 Imipramine (25) 12-wk RCT

n=56- + +

*Per protocol analysis NA = not assessed DB=double-blinded RCT=randomized controlled trial CC=comparator-controlled MC=multi-center study

Study DesignDrug (mg/day)Well-being

Global IBS symptoms

Abdominalpain relief

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Amitripyline for IBSTCAs effective at low doses

0

20

40

60

80

100

Intention to treat Per protocol

AMI 10 mg qHsPlacebo

8 week treatment period

** p<0.01 for eachNo significant difference in adverse events between groups

** **

Vahedi H et al. AP&T 2007.

Meta-analysis: SSRIs in IBS

Selective serotonin reuptake inhibitorsKuiken 2003Tabas 2004Vahedi 2005Tack 2006Talley 2008

Subtotal (95% CI) 113 117

9/1925/446/225/115/17

12/2136/4619/2211/125/16

5.8514.904.524.902.27

0.83 (0.45 to 1.51)0.73 (0.54 to 0.98)0.32 (0.16 to 0.64)0.50 (0.25 to 0.97)0.94 (0.33 to 2.65)

32.44 0.62 (0.45 to 0.87)

Total events: 50 treatments; 83 controlsTest for heterogeneity: X2 = 6.46, df = 4, (P=.17), I2 = 38.1%

Test for overall effect: Z = 2.74 (P=.006)

Fewer, smaller studies to date.

Number needed-to-treat (NNT) using SSRIs in IBS = 4Anecdotally, less effective than TCAs for abdominal pain.

Ford AC et al. Gut 2009.

Ford AC et al. Gut 2009 Mar;58(3):367-78.Ford AC et al. Am J Gastroenterol 2014.

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Antidepressants in FGIDOverview of options

TCAs SSRIs SNRIsAgents Amitriptyline,Desipramine

NortriptylineFluoxetine, Sertraline, Paroxetine, Citalopram

Duloxetine, VenlafaxineDesvenlafaxine, Milnacipran

Dose range 10-200 mg (start low, go slow!)

10-100 mg 30-90 mg (duloxetine)75-225 mg (venlafaxine)

Adverse effects SedationConstipationDry mouth/eyesWeight gainHypotensionSexual dysfunction

InsomniaDiarrheaNight sweatsWeight lossAgitationSexual dysfunction

NauseaAgitationDizzinessFatigueLiver dysfunctionConstipation

Time to action Few days to 2 weeks (low doses)2-6 weeks (high doses)

3-6 weeks 3-6 weeks

Efficacy Good for IBS and FD Good (IBS>FD); consider with + mood disorder

Limited studies (IBS>FD?)Good global response

Dose adjustments

Common Minimal Common

TCA=tricyclic antidepressant; SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin-norepinephrine reuptake inhibitor

Grover M, Drossman DA. Gastrointest Endoscopy Clin N Am. 2009;19:151-170.

Buspirone, a 5-HT1D agonistImprovement in dyspeptic symptoms

Rx: Buspirone 10 mg tid for 2 weeks

àPain benefit associated with changes in gastric accommodation Tack J et al. CGH 2011.

2

4

6

8

10

12

14

0

PLACEBO BUSPIRONE

Baseline BaselinePost-Rx Post-Rx

**

Dysp

epsi

a se

verit

y sc

ore

(DSS

)

** p<0.005 vs PBO

6

8

10

12

14 PLACEBO BUSPIRONEAnecdotally, excellent adjunct with TCAs for abdominal pain

Few drug interactions, very well tolerated

Titrate slowly (start 5 mg qd for 1 wk, then 5-7.5 mg bid)

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IBS PharmacotherapyRemember when?

IBS PharmacotherapyTegaserod for IBS with constipation

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Tegaserod for IBS with constipation“Not all smiles”

• March 30, 2007, the Food and Drug Administration (FDA) “discontinued marketing” of tegaserod“for safety reasons.”

• Retrospective review of 29 premarketing trials involving 11,614 tegaserod-treated subjects and 7,031 subjects who were treated with placebo found a 10-fold increase in the RR of significant pooled cardiovascular events:

• 0.1% in tegaserod-treated patients vs. with 0.01% in placebo • Number needed to harm (NNH) was 1,111

• FDA: because tegaserod was used for a “nonlife-threatening condition”, risk of serious

cardiovascular events was felt to be disproportionate to any potential benefit.

Brandt LJ. Am J Gastroenterol 2008.

• Large matched, case control study of tegaserod-treated patients (n = 2603), matched 1:6 with untreated (n = 15,618) patients, followed for an average of 2.5 years.

• Cardiovascular event rates were low and similar in patients treated with tegaserod and matched untreated patients. – Primary composite CV endpoint, 54 (0.35%) untreated and 12 (0.46%) treated pts had an event (treated OR

= 1.27, 95% CI: 0.68-2.38, P =.46), with 7 and 0 events, respectively, occurring within 3 months. – A total of 12 (0.1%) untreated and 1 (<0.1%) treated pts were hospitalized for a myocardial infarction (MI). – 36 (0.2%) untreated and 10 (0.4%) treated pts for a cerebrovascular accident, and 1 pt in each group for

unstable angina. – A total of 6 (<0.1%) untreated and no treated pts died from cardiac causes. Event rates were comparable to

expected rates in this population of mostly premenopausal women.

• Failed to confirm a reported large event differential for tegaserod incidentally noted in earlier clinical trials database– Suggesting that the prior observation may have been due to chance.

Tegaserod for IBS with constipationEvidence against a CV risk

Anderson JL, et al. J Cardiovasc Pharmacol Ther 2009.

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IBS Pharmacotherapy“What’s old is new again?”

IBS Pharmacotherapy“What’s old is new?”

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1. Tenapanor blocks NHE3, which transports sodium in exchange for protons

2. Blocking NHE3 increases sodium outside cells/in the gut

3. Increased sodium increases water in the gut, improving stool consistency,

alleviating constipation

IBS PharmacotherapyWhat’s New: Tenapanor for IBS-C?

Data from preclinical studies have shown that tenapanor works to reduce abdominal pain caused by IBS-C through the inhibition of TRPV-1 dependent signaling.

Source: Ardelyx website (www.ardelyx.com); accessed 10/27/18

Tenapanor for IBS-C?T3MPO-2 phase 3 study

0%

10 %

20 %

30 %

40 %

50 %

60 %

Abd Pain+CSBM* CSBM Abdomi nal pain Abd Pain+CSBM CSBM Abdomi nal pain

Tenapanor Placebo

* Primary study endpointComplete spontaneous bowel movement (CSBM) endpoint: Weekly increase in ≥1 CSBM from baseline and at least 3 CSBMs/weekAbdominal pain endpoint: ≥30% decrease in abdominal pain (0-10 scale) from baselineCombined Responder endpoint (Abd pain + CSBM): Both CSBM and abdominal pain endpoints met during the same week

≥6/12 study weeks ≥9/1st 12 study weeks AND ≥3/weeks 9-12(“Durable response”)

Source: Ardelyx website (www.ardelyx.com); accessed 10/27/18

50 mg of tenapanor (n=293) or placebo (n=300) twice-daily for 26 weeks

P<0.001

P<0.001P=0.004

% R

espo

nder

P<0.001P<0.001

P=0.028

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IBS

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What are FODMAPs?

Lentils, cabbage, brussels sprouts, asparagus,

green beans, legumes

Sorbitol

Raffinose

Honey, apples, pears, peaches, mangos, fruit

juice, dried fruit

Apricots, peaches, artificial sweeteners, artificially

sweetened gums

Wheat (large amounts), rye (large amounts), onions,

leeks, zucchini

Excess Fructose

Fructans

Fermentable Oligo-, Di-, Monosaccharides And Polyols

Shepherd SJ, et al. Clin Gastroenterol Hepatol. 2008;6:765-771; Shepherd SJ, Gibson PR. J Am Diet Assoc. 2006;106:1631-1639.

FODMAP Components Effects of on H2 production (breath testing)

DRINKS (500 ml):Glucose (40g)Fructose (40g)Fructan (40g)Glucose (40g) + Fructose (40g)

Murray K, et al. Am J Gastroenterol 2014.

=50g fructose

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Effects of FODMAP Components on Small Bowel Water Content (SBWC)

Murray K, et al. Am J Gastroenterol 2014.

70

0 7 14 21

20

40

60 60

40

20

14 21

Low FODMAP diet

FODMAP Diet in IBSReduces Functional GI Symptoms

Halmos EP et al. Gastroenterology 2014.

Effects of Diet on Functional GI Symptoms

in Controlled, Crossover Study (N=30)

VA

S (

0-1

00

mm

)

Study DayStudy Day

Typical Australian dietTypical Australian diet

Low FODMAP diet

FODMAP, fermentable oligo-di-monosaccharides and polyols; VAS, visual analog scale..

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Dietary Management of IBSIs FODMAP superior to ‘usual IBS diets’?

Eswaran SL et al. Am J Gastroenterology 2016.

• Single center RCT, 92 IBS-D patients randomized to FODMAP or Modified National Institute for Health and Care Excellence (UK) for 4 weeks

Dietary Management of IBSFODMAP > mNICE for abdominal pain and bloating

○§ §

§

1

2

3

4

5

6

Ba se lin e We ek 1 We ek 2 We ek 3 We ek 4Aver

age

Dai

ly A

bdom

inal

Pai

n Sc

ores

(0

-10)

m- NI CE Low FODM A P

#§ § §

1

2

3

4

5

6

Ba se lin e We ek 1 We ek 2 We ek 3 We ek 4

Aver

age

Dai

ly A

bdom

inal

Blo

atin

g Sc

ore

(0-1

0)

m- NI CE Low FODM A P

Abdominal Pain Scores Bloating Scores

P values refer to the change WITHIN group comparing to baseline score.*P≤0.05; oP≤0.001; §P≤0.0001.

Eswaran SL et al. Am J Gastroenterol 2016.

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FODMAP vs. mNICENo difference in adequate relief of IBS symptoms

4152

0

10

20

30

40

50

60

“In the last week, have you had adequate relief of your GI symptoms?”Proportion of patients that answered “Yes” for ≥50% of weeks 3 and 4

N=45mNICE Low FODMAP

N=38

Patie

nts w

ith

Adeq

uate

Rel

ief,

%

Adequate ReliefP=0.3055

mNICE: modified National Institute for Health and Care Excellence diet (see https://www.nice.org.uk/guidance/cg61/chapter/1-Recommendations#dietary-and-lifestyle-advice). Patients instructed to eat small frequent meals, avoid food triggers and excess alcohol and caffeine. FODMAP containing foods were not excluded from the mNICE diet.

Eswaran SL et al. Am J Gastroenterology 2016.

FODMAP vs. mNICEDifferences in macronutrient consumption

Eswaran SL et al. Am J Gastroenterology 2016.

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Gluten free diet for IBS

No significant impact on symptoms

2018 ACG Monograph: “We suggest against a gluten-free diet”

(Recommendation: Weak, Quality of Evidence: Low)

Ford AC et al. Am J Gastroenterol 2018.

Composition and Distribution of Gut Microbiota1

ÈBifidobacteria

ÈLactobacilli

ÈAnaerobes

ÇEnterobacteria

ÇAerobes

SHOULD WE USE PROBIOTICS?

Microbiome Shifts in IBS2*

*Determined by culture. Other microbiome shifts demonstrated by microarray, qPCR (quantitative polymerase chain reaction, DGGE (denaturing gradient gel electrophoresis, and FISH (fluorescence in situ hybridization). MMC, migrating motor complex.

Adapted from Simren M, et al. Gut. 2013;62:159-176; 2. Mayer EA, et al. Gastroenterology. 2014;146:1500-1512.

Gut microbiota are altered in IBS

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Probiotics for IBSBest evidence with combination and Bifidobacterium preparations

• 53 RCTs involving 5455 IBS patients

• Overall, superior to placebo (RR of IBS not improving = 0.81, 95% CI 0.74-0.88), NNT=7

• Improvement in global IBS symptoms, abdominal pain, bloating, and flatulence

• Insufficient and conflicting data prevent making recommendations about any individual species, preparation, or strain.1

• Multiple microbiologic studies demonstrate that probiotics do not contain viable bacterial species as listed on the label.2-5

• ACG Monograph: Recommendation: weak, Quality of Evidence: very low

1. Ford AC et al. Am J Gastroenterol 2018. 2. 2. Sanders ME, Levy DD. Ann NY AcadSci. 2011 3. Yeung PS et al. J Dairy Sci. 2002. 4. Temmerman R et al. Int J Food Microbiol. 2003. 5. Drisko J et al. Dig Dis Sci. 2005

Prebiotics for IBSAs effective as low FODMAP(with continued benefit)

LFD = low FODMAP dietHuaman et al. Gastroenterol 2018.

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-22.6 -19.2-25.4

-42.4-34.1

-48.1

0

20

40

60

80

100

Abdo minal Painor Discomfor t

Abdo minalBloating orDistension

Pain atEvacuation

Sym

ptom

red

uctio

n, %

AEs, adverse events; RCT, randomized controlled trial; TISS, Total IBS Symptom Score

Triple-Coated Peppermint Oil for IBSEffective for overall symptom improvement

Placebo TID (n=37)

Peppermint oil 180 mg TID (n=35)

**

*

Symptom Reduction at Day 29• RCT of triple-coated peppermint oil

microspheres in IBS-M or IBS-D (N=72)Ø Randomized to peppermint oil†

180 mg TID or placebo for 4 weeks

Ø Primary analysis based on TISS

• Peppermint oil improved TISS (P<0.02) and frequency and intensity of individual IBS symptoms over 4 weeks

• Most frequent AE with peppermint oil and placebo was dyspepsia/heartburn (2.9% vs 0%)

• Results may not extrapolate to other peppermint/menthol preparations

• NNT of 4

* p<0.05

Cash BD et al. Dig Dis Sci. 2016;61:560-571.

STW 5 for IBSImprovement in global symptoms and abdominal pain

N=208 IBS subjects, randomized to STW 5 (n=52, proprietary commercially available 9 plant extract), STW 5-II (experimental plant extract), bitter candytuft extract, or placebo

Madisch A et al. Aliment Pharmacol Ther 2004.

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Fiber Supplements for IBSSoluble fiber (psyllium)>insoluble (bran)

• 15 RCTs involving 946 IBS patients

• Significant effect of fiber vs. placebo– RR of IBS not improving =0.87, 95% CI 0.80-0.94)

– Bran had NO significant effect (RR=0.90, 95% CI 0.79-1.03)

• May ferment, exacerbate pain and gas-bloat symptoms

– Ispaghula effective in treating IBS (RR=0.83, 95% CI 0.73-0.94)

• Low cost, lack of side effects make soluble fiber a reasonable therapy– Improved stool viscosity, frequency in IBS-C

• ACG Monograph: Recommendation: strong, Quality of evidence: moderate

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Sleep and Hyperalgesia

“Good sleep”: ≥8 hoursBad sleep: <3 hours

1. Hiestand D et al. Chest 2006. 2. Chiu Y et al. Pain 2005. 3. Hakki Onen S et al. J Sleep Res 2001. 4. Schey R et al. Gastroenterol 2007. 5. Finan PH et al. J Pain 2013.

• Sleep deprivation (<7 hours night) is common, may affect up to 70% of adults1

• Subjects with self-reported disturbances in sleep have lower pain thresholds2

• Decreased tolerance thresholds to mechanical and thermal pain during sleep deprivation using a pressure dolorimeter and a thermode3

• Increased acid sensitivity in both healthy individuals and GERD patients with “bad sleep”4

• May relate to dysregulation of mu-opioid receptor responses to endogenous opioidergic system5

Disturbed Sleep and IBSA potential target for intervention?

Sleep duration (mins)

Longer undisturbed sleep episode

Mean sleep episode duration

Waking episodes during sleep

• IBS subjects (n=24) and healthy controls (n=26) monitored for 1 week with sleep actigraphy and daily symptom journals

• Poor sleep (waking episodes) predictive of worse GI symptoms in IBS only

• Sleep disturbances not related to GI symptoms

• Recommend focus on: sleep hygiene, caffeine/EtOH avoidance, no late meals, sunlight during day, melatonin

Patel A et al. Aliment Pharmacol Ther 2016.

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• Exercise protective against GI symptoms1 and improves colon transit2 in healthy volunteers

• IBS subjects (N=75) randomized to supervised physical activity or to maintain their lifestyle for 12 weeks2

• Increased physical activity improved IBS-SSS scores (P=0.003)

• Proportion of patients with worsened IBS symptoms was significantly higher in control group than in physical activity group

• Long term follow-up study (n=39, median 5 years): continued increased activity, symptom improvement3 1.

2. Johannesson E et al. Am J Gastroenterol. 20113. Johanesson E et al. World J Gastroenterol 2015.

IBS

Seve

rity

Sco

re

500

400

300

200

100

0

Control group Physical activity group

P = 0.001

Start 12 Weeks

Exercise for IBSImproved symptom severity with a durable effect

Yoga for IBS PatientsGood for the body (and the bowel!)

• 6 RCTs, n=273 IBS patients– In meta-analysis, beneficial effect of a yogic

intervention over conventional IBS treatment in IBS

– Significantly decreased bowel symptoms, IBS severity, and anxiety.

• Improvements in quality of life, global improvement, and physical functioning

• Yoga comparably effective as low FODMAP diet

Schumann D et al. Clin Gastroenterol Hepatol 2016.Schumann D et al. Aliment Pharmacol Ther 2017.

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Lackner J et al. Gastroenterol 2018.

Cognitive Behavioral Therapy (CBT) for IBSMinimal contact (and standard) CBT improves refractory IBS symptoms

IBS Management: Small Steps to Big ImprovementsA golf analogy

“Drive for show, putt for dough.” --Arthur D'Arcy "Bobby" Locke (1917 –1987)

Pharmacotherapy DietExercise/yoga

SleepPsychologicalSupplements

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