managing ibs patients dr sameer zar mbbs frcp phd consultant gastroenterologist epsom & st...
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Managing IBS patients
Dr Sameer ZarMBBS FRCP PhD
Consultant GastroenterologistEpsom & St Helier NHS Trust
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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
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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
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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
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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
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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
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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
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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
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Graded Treatment ResponseS
ympt
om s
ever
ity
Severe
Moderate
Mild
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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?
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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
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Treatment Approach
• Effective Physician-Patient Interaction
• Symptom Pattern– Diarrhoea Predominant
– Constipation Predominant
– Mixed/Alternating
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Long Transit(e.g. 100 hrs)
Short Transit(e.g. 10 hrs)
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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
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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
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IBS with Constipation (IBS-C)
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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
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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
(%)
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Long-Term Effectiveness of PEG in Chronic Constipation
% of patients
Dipalma JA et al. Am J Gastroenterol. 2007
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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
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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
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IBS with Diarrhoea (IBS-D)
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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
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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
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Other medications for IBS-D
• Antispasmodics
• Tricyclic antidepressants
• Rifaximin
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Abdominal Bloating in IBS
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Abdominal Pain in IBS
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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
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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
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Rationale for Antidepressants
Talk about these as ‘central pain modulators’ rather than antidepressants
Moderate to Severe IBS-D
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Antidepressant Receptor Site Effects
NE 5HT Histamine Ach
TCAs
Amitryptyline +++ +++ ++++ ++++
Doxepin ++ +++ ++++ ++
Desipramine +++ +++ + +
Nortriptyline +++ + ++ ++
SSRIs
Citalopram - ++++ - -
Escitalopram - ++++ - -
Fluoxetine - ++++ - -
Paroxetine - ++++ - -
Sertraline - ++++ - -
SNRI’s
Venlafaxine ++ ++ - -
Duloxetine +++ +++ - -
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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?
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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
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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
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Treatment Approach
• Effective Physician-Patient Interaction
• Symptom Pattern– Diarrhoea Predominant
– Constipation Predominant
– Mixed/Alternating
• Severity – Mild, Moderate, Severe
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Graded Treatment ResponseS
ympt
om s
ever
ity
Severe
Moderate
Mild
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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 + ++ +++
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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
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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
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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