Managing IBS patients

Dr Sameer ZarMBBS FRCP PhD

Consultant GastroenterologistEpsom & St Helier NHS Trust

Background

IBS affects 17 - 25% of general population

Approx. 50% IBS patients seek health care (predictors are age, female gender, abdominal pain, psychological distress)

IBS accounts for 30 – 50% referrals to gastroenterology clinics

Controversy whether IBS is a distinct disease entity or represents several different disease processes

98% no changein diagnosis

88% have symptoms

n=5952n=59521-8 years1-8 years

n=398n=3982-32 Years2-32 Years

median ? yearsmedian ? years

IBS - Prognosis

Genetics - IBS clusters in families

1 5 3 p are n ts /sib lin gsre sp on d ed5 3 fa m ilies

3 6 3 pa re n ts /s ibsu rve yed

2 0 9 e lig ib le

7 4 re spo n d e rs6 4 w ith liv ing re la tives

9 8 p a re n ts /sib lin gsre sp on d ed4 2 fa m ilies

2 9 9 pa re n ts /s ibsu rve yed

1 4 6 e lig ib le

6 2 spo u se s resp on d ed5 8 w ith liv ing re la tives

1 8 1 IB S9 1 IB S c la ss

9 0 d ia g n os tic in d ex

0

2

4

6

8

10

12

14

16

18

OR 2.72, 95% CI 1.19-6.25

Pts relatives Spouses relatives

Kalanatar et al. Gut 2003; 52: 1703-7

Pathophysiological model of IBS

Psychosocial Factors

•Life stress•Psychological state•Coping•Social support

Physiology•Motility•Sensation

•Genetics•EnvironmentBacterial FloraFood Hypersensitivity

IBS•Symptom experience•Behaviour

Outcome•Medication•Surgery visits•Daily function•QoL

CNS ENS

Drossman DA et al, Gastroenterology 2002, 123:2108-2131

Diagnosis of IBS - Rome III Criteria

Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with 2 or more:

Longstreth G., Gastroenterology 2006

Improvement with defecation

Onset associated with change in form (appearance) of

stool

Onset associated with

change in frequency of

stool

and/orand/or

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

Initial Evaluation Rome Recommendations

• Physical Examination

• Full blood count

• ESR

• Stool testing– Occult blood

– O & P

– M, C & S

• Sigmoidoscopy/

Colonoscopy

• Additional studies if needed

IBS Diagnosis

Is screening for coeliac disease justified in IBS patients?

0%

1%

2%

3%

4%

5%

IBS (n=300) Control(n=300)

IBS (n=300)

Control (n=300)

Ig TTG negative but IgG or IgA AGA positive

True positive 3

False positive 51

IgA TTG positive

True positive 11

False positive 1

Sanders et al. Lancet 2001

Graded Treatment ResponseS

ympt

om s

ever

ity

Severe

Moderate

Mild

Treatment Approach

Effective Physician-Patient Interaction

Attentive listening/Silence

How long does a patient talk when asked an open question?

How soon is the patient interrupted before he completes talking?

IBS Physician Patient Relationship

Guidelines• Identify concerns

• Explain basis for symptoms

• Reassure

• Cost effective evaluation

• Involve patient

• Provide Continuity

• Set realistic limits

Drossman at al, Gastroenterology 1992;116;1008

Owens et al Annals of Int Med;1995:122;107

Treatment Approach

• Effective Physician-Patient Interaction

• Symptom Pattern– Diarrhoea Predominant

– Constipation Predominant

– Mixed/Alternating

Long Transit(e.g. 100 hrs)

Short Transit(e.g. 10 hrs)

Rome III IBS Subtypes

IBS-C IBS-MType 1,2 .

IBS-U IBS-D Types 6,7

% BM Loose or watery0 25 50 75 100

% B

M H

ard

or L

umpy

100

75

50

25

0

25% of BM is the threshold forclassification

Available IBS Treatments

Abdominal Pain /

discomfort

Defecatorydisorder

Bloating Tegaserod Probiotics ?Antibiotics ?Exclusion diet

Constipation Fibre Osmotic laxatives (Movicol) Tegaserod /Prucalapride Lubiprostone Biofeedback (Dyssynergia) Surgery (Colonic Inertia)

Abdominal Pain Anticholinergics Antidepressants Alosetron (IBS-D) Tegaserod (IBS-C)

Altered bowel

functionDiarrhoea Anticholinergics Loperamide/Diphenoxylate Probiotics Clonidine Cholestyramine Alosetron

IBS with Constipation (IBS-C)

Efficacy of Fibre in IBS

• Evidence for Ispaghula– 6 studies, 321 patients

– Significant effect on overall IBS symptoms

– RR = 0.78; 95% CI = 0.63 to 0.96

– NNT = 6 (95% CI = 3 to 50)

• Recommendation– Bran has not been shown to be useful in IBS

– Use in mild-moderate IBS

– More effective in IBS-C

– May need to start with lower dose (e.g. 1 tsp/day) and then increase as needed and tolerated

Ford AC et al. BMJ 2008; 337;a2313

Lubiprostone in IBS-C

• Efficacy in clinical trials– Significantly higher overall

response vs. placebo1

– Grade 1B2

• What actually helps– Start at 8μg bid

– Can increase to 24μg bid if needed

– Take with meals to reduce nausea

1 Drossman DA, et al. Gastroenterology. 2007;132;2586-25872 ACG IBS Task Force, AM J Gastro 2009; 104 (S1); S1-S35

Pts

ach

ievi

ng r

espo

nse

(%)

Long-Term Effectiveness of PEG in Chronic Constipation

% of patients

Dipalma JA et al. Am J Gastroenterol. 2007

Laxatives in IBS

• Polyethylene glycol (PEG)– Improved stool frequency but not abdominal

pain in IBS-C– Laxatives help constipation symptoms– Partially help bloating and pain/discomfort– Overuse can worsen symptoms

ACG IBS Task Force, Am J Gastro 2009

Prucalopride in IBS

• Stimulates colonic activity and transit (5HT-4 receptor)

• Dose 2mg od (age <65yrs) & 1mg od (age>65)

• Women with chronic constipation

• Failed treatment at least two other types of laxatives and lifestyle changes for 6 months

• SE: abdominal pain, nausea, headache & diarrhoea

• Increase in bowel movements to 3 or more per week (Prucalopride 30% vs. placebo 11%, p<0.001

Nice Guidelines 2011

IBS with Diarrhoea (IBS-D)

Loperamide for IBS-D

• Efficacy in clinical trials– Not more effective than placebo at reducing pan,

bloating, or global symptoms of IBS, but it is effective for the treatment of diarrhoea, reducing stool frequency, and improving stool consistency (Grade 2C)

• What actually helps– Use prn for episodic diarrhoea– Use proactively– Start with low dose to avoid constipation– Can use up to 2 tablets qid for more severe diarrhoea

ACG IBS Task Force, Am J Gastro 2009

5HT3 Antagonists: Alosetron

• Clinical trial results1

– 8 studies, 4987 patients

– RR symptom remain = 0.79 (95% CI 0.69 to 0.90)

– NNT = 8 (95% CI = 5 to 17)

• Indication – women with severe IBS-D• What really helps

– Start with 0.5mg bid

– Teach patient to titrate dose to avoid constipation and relieve pain and diarrhoea

– Monitor for constipation and ischemic colitis1Ford AC et al. Am J Gastroenterol 2009

Other medications for IBS-D

• Antispasmodics

• Tricyclic antidepressants

• Rifaximin

Abdominal Bloating in IBS

Assess Factors Contributing to Bloating and Gas in IBS

• What goes in– Diet history and relationship to symptoms; food and symptom

diary

– Assess lactose and fructose intolerance

– FODMAPs diet1

• What goes out– Slowed transit and altered gas handling

– Need to treat constipation

• What they feel– Increased visceral perception

1Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols; includes fructose, fructans, raffinose, polyols

1Shepherd et al. Clin Gastroenterol Hep 2008

Overall Improvement of IBS with Rifaximin10 Weeks Follow-up

Moderate to Severe IBS

0

10

20

30

40

50

0 1 2 3 4 5 6 7 8 9 10

Time Beyond Treatment (wk)

Impr

ovem

ent (

%)

Rifaximin Placebo

Pimentel M, et al. Ann Intern Med. 1006:145;557

Rifaximin in IBS

– Patient selection: mild-moderate severity, bloating and gas, IBS-D and IBS-M

– Breath tests may not predict treatment response

– Use at least 1200mg/day x 10 days

– Lack of data on lengthening duration of response and repeated treatment

ACG IBS Task Force, Am J Gastro 2009

IBS – Luminal Microbial Environment

Injurious Pro-inflammatory

Bacteroides vulgatusEnterococcus faecalisE. coli (enteroadherent/ invasive)

ProtectiveProbiotics

Lactobacilliyus sp.

Bifidobacterium sp.

Non-pathogenic E. coli

Mild to Severe IBS

Probiotics

• Evidence– 18 trials, 1650 patients1

– RR symptoms remain = 0.71 (95% CI = 0.57 to 0.88)

– NNT= 4 (95% CI = 3 to 12.5)

– Only probiotic to demonstrate efficacy in appropriately designed RCTs in B infantis 356242

• Recommendation– Patient selection: milder severity, bloating and gas symptoms

– Not clear if one is better than other in clinical practice

– Lack of quality data on available probiotics

1Moayyedi P et al. Gut, Dec 20082Brenner DM et al. Am J Gastroenterol. 2009

Selection of Patients for Antibacterial Therapy in IBS

Does patient fit clinical profile of bacterial overgrowth:Postprandial abdominal discomfort, bloating and loose stools

Antibiotic

Maintenance with a probiotic

Consider prokinetic to accelerate small bowel transit

Repeat breath study, treat only if positive or

Sustained response (>6months)

Stool normalises orconstipation

Symptoms recur, previous test +

? H2 Breath Test

Food Hypersensitivity in IBS

20 – 65% of IBS patients attribute symptoms to adverse food reactions

Estimated prevalence of food hypersensitivity is 1.4 – 1.8% in general population

Young et al, Lancet 1994; 343: 1127-30

Exclusion diets may be beneficial in IBS patients

Exclusion Diets in IBS

N Response rate Double blind

Jones et al 1982 25 67% Yes

Bentley et al 1983 19 16% Yes

Farah et al 1985 49 27% No

Petitpierre et al 1985 24 20% No

McKee et al 1987 40 27.5 No

Nanda et al, 1989 200 48% No

Food specific IgG4 antibodies in IBS

PorkBeefLambWheat

IgG

4 A

ntibody titre

s (ug/l)

3500

3000

2500

2000

1500

1000

500

0

-500

C-IBS

D-IBS

A-IBS

Control

Zar et al, AJG 2005

Effect of Exclusion Diet on Symptom Severity Score

6-month3-monthBaseline

Sym

pto

m S

core

on V

AS

(M

ean +

/- 2

SE

M)

100

90

80

70

60

50

40

30

20

10

0

Pain Severity

Pain Frequency

Bloating Severity

Bowel Habits

Life in General

Effect of exclusion diet in IBS

Zar et al. Scand J Gastroenterol 2005; 40(7): 800-7

IgG4 guided exclusion diet in IBS

Symptom severity scoreMean worsening 83.3

24% w orse vs sham (p=0.003)

Rechallenge(n=41)

Symptom severity scoreMean improvement 100

'True die t' x 12 w k(n=65)

Symptom severity scoreMean worsening 31

Rechallenge(n=52)

Symptom severity scoreMean improvement 61.5

'Sham diet' x 12 w k(n=66)

Patien ts randomised (n=150)Intention to treat analysis

Atkinson et al, Gut 2004; 53: 1459-1464

10 lost to f/up

9 lost to f/up

Abdominal Pain in IBS

Antispasmodics in IBS

• Evidence– 22 studies; 12 antispasmodics; 1778 patients

– Overall symptoms improvement vs. placebo: 61% vs. 44%

– RR symptoms remain = o.68 (95% CI = 0.57 to 0.81)

– NNT = 5 (95 % CI = 4 to 9)

• Recommendation– Use in patients with intermittent symptoms

– Can help decrease post-prandial pain

– Use proactively, i.e. 30 min before meals

– Chronic use can cause constipation, dry mouth, ?loss of response

Ford AC et al. BMJ 2008

Rationale for Antidepressants

• Peripheral effects

– Motility / secretion

– Afferent

• Central pain modulatory effects

• Treatment of psychiatric co-morbidity (in higher doses)

Moderate to Severe IBS-D

Rationale for Antidepressants

Talk about these as ‘central pain modulators’ rather than antidepressants

Moderate to Severe IBS-D

Antidepressant Receptor Site Effects

NE 5HT Histamine Ach

TCAs

Amitryptyline +++ +++ ++++ ++++

Doxepin ++ +++ ++++ ++

Desipramine +++ +++ + +

Nortriptyline +++ + ++ ++

SSRIs

Citalopram - ++++ - -

Escitalopram - ++++ - -

Fluoxetine - ++++ - -

Paroxetine - ++++ - -

Sertraline - ++++ - -

SNRI’s

Venlafaxine ++ ++ - -

Duloxetine +++ +++ - -

Antidepressant Treatment

TCA SSRI SNRI

Potential Benefit

Pain

Depression

?Pain

Depression, panic, anxiety, OCD

Pain

Depression

Adverse events

Sedation, hypotension, Constipation, dry mouth, arrhythmias, weight gain, sexual dysfunction

Insomnia, Agitation, Diarrhoea, headaches, night sweats, weight loss, Sex dysfunction

Nausea, Agitation, Dizziness, Sleep disturbance, Fatigue, Liver Dysfunction

Efficacy for IBS

Good Not studied Good?

Guidelines for Using Central Agents

• Desipramine (TCA)– Fair evidence of pain/diarrhoea benefit– Less sedation/constipation than Amitriptyline

• Duloxetine (SNRI)– Pain benefit– Not much effect on bowel function

• SSRIs– Anxiolytic– Can help constipation

• Buspirone– Anxiolytic– Augmentation treatment– Gastric accomodation

• Mirtazepine– For nausea and weight loss

• Quetiapine (Atypical antipsychotic)– For augmentation, sedation, extreme anxiety, sleep

Pain &Narcotic Vicious

Cycle

Pain &Narcotic Vicious

Cycle

Narcotics pain relief

Narcotics pain relief

Delayed Transit

Delayed Transit

Constipation / Ileus

Constipation / Ileus

DistensionDistensionIncreased intestinal

spasm / painIncreased intestinal

spasm / pain

NarcoticsNarcotics

Nausea /VomitingNausea /VomitingWithdrawalWithdrawal

Treatment Approach

• Effective Physician-Patient Interaction

• Symptom Pattern– Diarrhoea Predominant

– Constipation Predominant

– Mixed/Alternating

• Severity – Mild, Moderate, Severe

Graded Treatment ResponseS

ympt

om s

ever

ity

Severe

Moderate

Mild

IBS - Clinical Spectrum

Mild Moderate Severe

Prevalence 45 – 55% 30-35% 15-20%

Practice typePrimary Specialty Referral

Symptoms Constant

- + +++

Altered Gut Physiology

+++ ++ +

Psychosocial difficulties

- + +++

Healthcare use + ++ +++

Benefits of Psychological Treatment

• High response rate (about 70%)

• Can benefit patients not responding to medical treatments

• Is additive to and possibly synergistic with medical treatments

• No side effects

• Benefits continue years after treatment ends

• Reduces health care costs

Limitations of Psychological Treatment

• Requires patient motivation– Needs to understand and accepts the process without stigma– Frequent visits– Home exercises– Treatment costs

• Requires trained therapist in community

• Therapist must be experienced working with with GI disorders

• Not widely available

• Usually requires ongoing medical treatment

Referral to Psychiatrist

Treatable psychiatric disorder Anxiety / panic Major depression

Poor adjustment to illness Psychosocial trauma affecting adjustment to illness

Major loss Abuse

Difficult therapeutic relationship Borderline personality disorder Factitious illness

Treatable psychiatric disorder Anxiety / panic Major depression

Poor adjustment to illness Psychosocial trauma affecting adjustment to illness

Major loss Abuse

Difficult therapeutic relationship Borderline personality disorder Factitious illness