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<strong>Guidelines</strong> on the irritable bowel syndrome: 

mechanisms and practical management 

R Spiller, Q Aziz, F Creed, A Emmanuel, L Houghton, P Hungin, R Jones, D 

Kumar, G Rubin, N Trudgill and P Whorwell 

Gut 2007;56;1770-1798; originally published online 8 May 2007; 

doi:10.1136/gut.2007.119446 

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1770 

GUIDELINES 

<strong>Guidelines</strong> on the irritable bowel syndrome: mechanisms and 

practical management 

R Spiller, Q Aziz, F Creed, A Emmanuel, L Houghton, P Hungin, R Jones, D Kumar, G Rubin, 

N Trudgill, P Whorwell 

................................................................................................................................... 

Gut 2007;56:1770–1798. doi: 10.1136/gut.2007.119446 

Supplementary documents 

are available at http:// 

gut.bmj.com/supplemental 

See end of article for 

authors’ affiliations 

........................ 

Correspondence to: 

Professor R C Spiller, The 

Wolfson Digestive Diseases 

Centre, University Hospital, 

Nottingham NG7 2UH, UK; 

robin.spiller@nottingham. 

ac.uk 

Revised 20 April 2007 

Accepted 1 May 2007 

Published online first 

8 May 2007 

........................ 

Background: IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth 

decades, with a female predominance. 

Aim: To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. 

Methods: Members of the Clinical Services Committee of The British Society of Gastroenterology were 

allocated particular areas to produce review documents. Literature searching included systematic searches 

using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases 

and extensive personal reference databases. 

Results: Patients can usefully be classified by predominant bowel habit. Few investigations are needed except 

when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse 

psychological features and somatisation are often present. Ascertaining the patients’ concerns and explaining 

symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, 

each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often 

improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive 

behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits 

global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; 

ispaghula improves pain and bowel habit; 5-HT 3 antagonists improve global symptoms, diarrhoea, and pain 

but may rarely cause unexplained colitis; 5-HT 4 agonists improve global symptoms, constipation, and 

bloating; selective serotonin reuptake inhibitors improve global symptoms. 

Conclusions: Better ways of identifying which patients will respond to specific treatments are urgently needed. 

1 SCOPE AND PURPOSE 

1.1 Aims 

These guidelines were compiled at the request of the Chairman 

of the Clinical Services Committee of the British Society of 

Gastroenterology. The committee’s aim was to provide a guide 

for the assessment and management of adult patients with 

irritable bowel syndrome (IBS). These patients comprise such a 

large proportion of gastroenterology outpatients that their 

streamlined and effective management would have a favourable 

effect on any gastroenterology department’s overall 

performance, and hence improve the management of all 

gastrointestinal diseases. There are many questions to be 

addressed (box 1). 

These guidelines are designed to be applied to adults with 

IBS, though they are also likely to apply to most adolescents. 

The guideline committee was chosen from members of the 

British Society of Gastroenterology, aiming to include individuals 

with a longstanding interest and expertise in the topics to 

be discussed. Members were chosen to be representative of the 

spectrum of individuals likely to see such patients, including 

general practitioners, gastroenterologists from district general 

hospitals and university hospitals, surgeons and clinical 

physiologists. 

People who suffer from IBS and members of the United 

Kingdom based IBS Network were also shown this document 

and their comments have influenced the final version. 

The guidelines are aimed primarily at consultant gastroenterologists 

and trainees in gastroenterology, together with 

general practitioners with a special interest in gastroenterology. 

A summary form of this document is available with ‘‘when to 

refer’’ advice for use in primary care (see page 82) which is 

available online at the Journal website (http://gut.bmj.com/ 

supplemental). 

1.2 Development of guidelines 

Members of the committee were allocated particular areas to 

produce review documents for. Literature searching included 

systematic searches using electronic databases such as Pubmed, 

EMBASE, MEDLINE, Web of Science, and Cochrane databases 

and extensive personal reference databases. Citation of the 

literature is however selective and in particular many low 

quality studies were discounted. Special attention was paid to 

high quality studies which used established methodology and 

substantial patient numbers with clearly defined entry criteria. 

For trials of treatment, randomisation and placebo control were 

considered essential. These documents were collated and edited 

by the Chairman, and the resulting document discussed at a 

one day face to face meeting. Detailed internal review by 

members of the committee was followed by revision and 

teleconferences to establish a consensus. These documents were 

sent out to patient groups and for external independent review, 

Abbreviations: CBT, cognitive behavioural therapy; CCK, cholecystokinin; 

CRF, corticotropin releasing factor; CRH, corticotrophin releasing 

hormone; EMA, endomysial antibodies; fMRI, functional magnetic 

resonance imaging; HPA, hypothalamo-pituitary-adrenal; IBS, irritable 

bowel syndrome; IBS-C, constipation predominant IBS; IBS-D, diarrhoea 

predominant IBS; IBS-M, IBS with mixed bowel pattern; MMC, migrating 

motor complex; NNT, number needed to treat; PIT, psychodynamic 

interpersonal therapy; RCT, randomised controlled trial; SSRI, selective 

serotonin reuptake inhibitor 

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<strong>Guidelines</strong> on the irritable bowel syndrome 1771 

both nationally through the BSG Clinical Services Committee 

and Council and internationally. The final document represents 

the consensus of the committee, adjusted in response to 

reviewers’ and patients’ comments. 

1.3 Link between supporting evidence and 

recommendations 

Evidence was graded according to the type of evidence, giving 

greatest emphasis to randomised, placebo controlled trials 

(RCTs). These grades were decreased if there were serious 

limitations to study quality, important inconsistencies between 

different studies, or uncertainty about the relevance of the 

particular study population for the group of patients under 

consideration. The grade was considered to be further reduced 

if data were sparse or there was a suggestion of reporting bias, 

but increased if the evidence of association was strong or if 

there was clear evidence of a dose–response gradient. 

Combining the elements of study design, study quality, 

consistency, and directness, we followed the GRADE working 

group advice 1 and categorised the quality of evidence as follows: 

N High—further research is very unlikely to change our 

confidence in the estimate of effect. 

N Moderate—further research is likely to have an important 

effect on our confidence in the estimated effect and may 

change the estimate. 

N Low—further research is very likely to have an important 

impact on our confidence in the estimated effect and is likely 

to change the estimate. 

N Very low—estimate of effect is very uncertain. 

In making recommendations for any intervention, we then 

considered the trade-off between benefit and harm, categorised 

as follows: 

N Net benefit—the intervention clearly does more good than 

harm. 

N Trade-off—there are important trade-offs between the benefits 

and harm. 

N Uncertain trade-off—it is not clear whether the intervention 

does more good than harm. 

N No net benefits—the intervention clearly does not do more 

good than harm. 

Our final recommendations are characterised slightly differently 

from the GRADE systems in that we classified as 

‘‘definitive’’ a judgment that most informed people would 

make, and as ‘‘qualified’’, a judgment that the majority of well 

informed clinicians would make but a substantial minority 

would not. 

It should be noted that many aspects of medical practice have 

not been formally evaluated using robust methodology; 

however, the committee still recommended some behaviours 

such as taking a careful history and listening to the patients 

Box 1 

Main questions to be addressed 

N What is the best way to identify IBS patients? 

N What are the minimum number of relevant investigations? 

N What is the optimum management? (This may include 

lifestyle adjustments, psychological treatments, dietary 

modification, and pharmacological treatments.) 

complaints as being not only self evident, but also part of the 

obligations of being a medical practitioner. 

Finally, we considered whether the intervention was likely to 

be cost-effective and what barriers there might be to its use in 

clinical practice. 

1.4 Scheduled review of these guidelines 

These guidelines are presented on the BSG website and are 

freely available to all. They should be reviewed and revised 

within four years, depending on changes in evidence and 

clinical practice. Comments on the guidelines should be sent to 

the authors or posted on the BSG notice board. 

1.5 Editorial independence 

This document represents a consensus view of the members of 

the working party and incorporates their response to reviewers’ 

comments. All members completed conflict of interest statements. 

2 EPIDEMIOLOGY 

2.1 Introduction 

IBS is a chronic, relapsing gastrointestinal problem, characterised 

by abdominal pain, bloating, and changes in bowel 

habit. While the precise prevalence and incidence depends on 

the criteria used, all studies agree that it is a common disorder, 

affecting a substantial proportion of individuals in the general 

population and presenting frequently to general practitioners 

and to specialists. IBS is troublesome, with a significant 

negative impact on quality of life and social functioning in 

many patients, 2–5 but it is not known to be associated with the 

development of serious disease or with excess mortality. IBS 

generates significant health care costs, both direct, because of 

IBS symptoms and associated disorders, and indirect, because 

of time off work. 

2.2 Definitions 

The first attempt to establish diagnostic criteria to define IBS 

was made in the 1970s by Manning and colleagues. 6 The 

Manning criteria (box 2) were identified by comparing 

symptoms in patients with abdominal pain who turned out 

either to have or not to have organic disease. 

Over the past 10 years considerably more attention has been 

paid to IBS, and the successive Rome working parties have 

elaborated more detailed, accurate, and useful definitions of the 

syndrome. The Rome I criteria, which were published in 1990, 7 

adopted most of the Manning criteria but subsequent factor 

analysis indicated that items 1–3 clustered well together while 

4–6 did not. 8 9 The Rome II criteria which appeared in 1999 10 

took account of this fact but also recognised that pain might be 

associated with hard as well as loose stools. The Rome III 

criteria in 2006 11 are shown in box 3. The majority of studies 

quoted below used Rome II criteria. Rome III modifies Rome II 

slightly by being more precise, specifying that pain must be 

present for three or more days a month in the past three 

months and that criteria need to be fulfilled for the past three 

months for the patient to be considered as currently having IBS. 

However, comparative studies suggest these subtle changes will 

have little effect on prevalence. 

The Rome III committee also advised that ‘‘in pathophysiology 

research and clinical trials a pain/discomfort frequency of at 

least two days a week is recommended for subject eligibility.’’ 

2.3 Classification 

Recently attempts have been made to subclassify IBS according 

to the predominant bowel habit. Most studies report that 

around one third of patients have diarrhoea predominant IBS 

(IBS-D) and one third have constipation predominant IBS 

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1772 Spiller, Aziz, Creed, et al 

(IBS-C), the remainder having a mixed bowel pattern (IBS-M) 

with both loose and hard stools. 12–14 However, most of the 

published data on the incidence, prevalence, and natural 

history of IBS do not distinguish these subtypes. Furthermore 

some individuals—now called ‘‘alternators’’ 11 —switch subtype 

over time, mostly those with IBS-D or IBS-C switching to a 

mixed pattern, though in one study a change from IBS-D to 

IBS-C occurred in 29% over a one year period. 14 

2.4 Prevalence 

Most of our knowledge of the descriptive epidemiology of IBS 

has been obtained from the use of validated postal questionnaires, 

employing either the Manning or the Rome criteria, 

completed by individuals in the general population. We were 

able to identify 37 epidemiological studies of acceptable quality 

(table 1). Prevalence appears generally higher and more 

variable using Manning criteria, while Rome I and II yield 

comparable but less variable results. The number of Manning 

criteria (one to six) strongly influences the prevalence 

estimates, which range from 2.5% to 37%. Studies which 

require three criteria give prevalences of around 10%. The 

incidence is similar in many countries in spite of substantial 

differences in lifestyle—for example, the incidence in Mexico is 

very similar to that in the USA. 45 

2.5 Predictors of health care seeking 

Consultation behaviour is likely to be an important determinant 

of the prevalence of clinically diagnosed IBS. It appears 

that 33–90% of sufferers do not consult, and that a proportion 

of consulters meeting IBS criteria are not labelled as having IBS 

by their clinicians. Although the prevalence of IBS is relatively 

similar across Europe and the USA (Italy being an exception, 

with a higher incidence than the rest), the rate of undiagnosed 

IBS shows a wider variation, with the majority being 

undiagnosed in all countries except for Italy and the United 

Kingdom, where around 50% are diagnosed. Most data on 

prevalence and health care seeking behaviour are from 

community based samples, indicating that health care seeking 

behaviour is greater in this population and not just in the group 

of IBS patients with severe or longstanding symptoms. The 

main predictors of health care seeking are abdominal pain or 

distension, pain severity, and symptoms conforming to the 

Rome II criteria, although psychological and social factors also 

play a key role in the decision to seek medical advice. 53–57 

Overall, health care seeking is greater in IBS patients than in 

16 17 58–62 

non-IBS patients. 

The frequency of IBS symptoms peaks in the third and fourth 

decades, and in most surveys there is a female predominance of 

approximately 2:1 in the 20s and 30s, although this bias is less 

apparent in older patients. 63 IBS symptoms persist beyond 

middle life, and continue to be reported by a substantial 

proportion of individuals in their seventh and eighth decades. 24 

Box 2 

Manning criteria 

1. Pain relieved by defecation 

2. More frequent stools at onset of pain 

3. Looser stools at onset of pain 

4. Visible abdominal distension 

5. Passage of mucus per rectum 

6. Sense of incomplete evacuation 

2.6 Natural history and prognosis 

Few studies have assessed the incidence of new cases of IBS, 

but those that have provide widely varying estimates of 

40 64–66 

incidence (2–70/1000 patient years). Most current IBS 

patients will have had symptoms for some years, the mean 

durations in recent clinical trials being 5, 11, and 13 years, 

depending on the source of the patients. 67–69 Such patients 

rarely develop other gastroenterological diseases, though the 

exact manifestations and stool pattern may change over the 

years. Once the diagnosis has been made, new diagnoses are 

rare and are likely to be coincidental. 70 Few studies have 

examined the progression of IBS over time. One study in 

Scandinavia studied the ‘‘stability’’ of the diagnoses of 

dyspepsia and IBS in the population over one and seven year 

periods. 65 This showed that 55% still had IBS at seven years, 

13% were completely symptom-free, while 21% had lesser 

symptoms, no longer meeting the Rome I criteria. 

It appears that IBS is not associated with the long term 

development of any serious disease 71 72 and there is no evidence 

that IBS is linked to excess mortality, although it has been 

shown that patients with IBS are more likely to undergo certain 

surgical operations, including hysterectomy and cholecystectomy, 

than matched non-IBS controls. 18 Prognosis depends on 

the length of history, those with a long history being less likely 

to improve. 73–76 

The other key prognostic factor is chronic ongoing life stress 

which virtually precluded recovery in one study in which no 

patient with ongoing life stresses recovered over a 16 month 

follow up, compared with 41% without such stresses. 77 

3 CLINICAL FEATURES OF IBS 

The key features are chronic, recurring abdominal pain or 

discomfort associated with disturbed bowel habit, or both, in 

the absence of structural abnormalities likely to account for 

these symptoms. Symptoms should be present for at least six 

months to distinguish them from those caused by other 

conditions such as infections, where the effects are often 

transient, or progressive diseases such as bowel cancer, which 

are usually diagnosed within six months of symptom onset. 

3.1 Symptoms 

As the Rome III criteria indicate (see 2.1), the key features are 

abdominal pain or discomfort which is clearly linked to bowel 

function, being either relieved by defecation (suggesting a 

colonic origin) or associated with change in stool frequency or 

consistency (suggesting a link to changes in intestinal transit, 

Box 3 

Rome III diagnostic criteria* for irritable bowel 

syndrome 

Recurrent abdominal pain or discomfortÀ at least 3 days a 

month in the past 3 months, associated with two or more of the 

following: 

N Improvement with defecation 

N Onset associated with a change in frequency of stool 

N Onset associated with a change in form (appearance) of 

stool 

*Criteria fulfilled for the past 3 months with symptom onset at 

least 6 months before diagnosis. 

À‘‘Discomfort’’ means an uncomfortable sensation not 

described as pain. 

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Table 1 Prevalence of irritable bowel syndrome in the United Kingdom and in other Western 

and Eastern populations, using Manning, Rome I, and Rome II diagnostic criteria 

Prevalence and criteria used (%) 

Country 

Sample size Manning Rome I Rome II 

Reference 

UK 301 13.6 Thomson & Heaton, 1980 15 

UK 1620 22 Jones & Lydeard, 1992 16 

UK 1896 9.5 Heaton et al, 1992 17 

UK 3179 16.7 Kennedy & Jones, 2000 18 

UK 3111 (PC*) 2.5 Thomson et al, 2000 19 

UK 4807 10.5 Wilson et al, 2005 20 

USA 789 17.1 Drossman et al, 1982 21 

USA 566 15.0 Sandler et al, 1984 22 

USA 835 8.7 to 17.0 Talley et al, 1991 23 

USA 325 4.9 to 10.9 Talley et al, 1992 24 

USA 5430 11.6 Drossman et al, 1993 25 

USA 3022 20.0 Talley et al, 1995 26 

USA 643 8.6 to 20.4 Saito et al, 2000 27 

USA 643 6.8 4.7 Saito et al, 2003 28 

USA 5009 14.1 Hungin et al, 2005 29 

Canada 1149 13.5 13.1 Thompson et al, 2002 30 

Canada 437 2.5 Li et al, 2003 31 

Australia 2910 16.7 Boyce et al, 2000 32 

New Zealand 980 18.8 3.3 Barbezat et al, 2002 33 

Netherlands 438 5.8 Boekema et al, 2001 34 

Spain 2000 4.4 to 13.6 Mearin et al, 2001 35 

Italy 533 8.5 Gaburri et al, 1989 36 

France 20,000 4.7 Coffin et al, 2004 37 

Denmark 4581 6.6 Agreus et al, 1995 38 

Finland 3631 9.7 to 16.2 5.5 5.1 Hillila & Farkkila, 2004 39 

Sweden 1290 14.0 Kay et al, 1994 40 

Iran 4762 5.8 Hoseini-Asl & Amra, 2003 41 

Turkey 998 19.1 Karaman et al, 2003 42 

Turkey 1766 6.3 Celebi et al, 2004 43 

Bangladesh 2426 8.5 Masud et al, 2001 44 

Hong Kong 1000 6.6 Kwan et al, 2002 46 

Hong Kong 1298 17.4 3.7 Lau et al, 2002 47 

Japan 231 25.0 Schlemper et al, 1993 48 

Singapore 696 2.3 Ho et al, 1998 49 

South China 4178 13.0 Xiong et al, 2004 50 

Singapore 2276 11.0 10.4 8.6 Gwee et al, 2004 51 

Malaysia 949 15.7 Rajendra & Alahuddin, 2004 52 

*PC, primary care patients. 

which might reflect changes in either motor patterns or 

secretion). 

Symptoms that are common in IBS but not part of the 

diagnostic criteria include those originally described by 

Manning 6 —namely, bloating, abnormal stool form (hard and/ 

or loose), abnormal stool frequency (,36/week or .36/day), 

straining at defecation, urgency, feeling of incomplete evacuation, 

and the passage of mucus per rectum. Most patients 

experience symptoms intermittently, with flares lasting two to 

four days followed by periods of remission. 78 79 One important 

exception is the subgroup of patients with pain which is felt 

continuously. The diagnosis in this case is usually ‘‘functional 

abdominal pain’’, an unusual and particularly severe condition 

which needs early recognition, as such patients respond poorly 

to conventional treatment and often have severe underlying 

psychological disturbances. 80 

Box 4 

Helpful diagnostic behavioural features of irritable 

bowel syndrome in general practice: 

Symptoms present for more than 6 months 

Frequent consultations for non-gastrointestinal symptoms 

Previous medically unexplained symptoms 

N Patient reports that stress aggravates symptoms 

IBS is considered a painful condition and those with painless 

bowel dysfunction are labelled as having ‘‘functional constipation’’ 

or ‘‘functional diarrhoea’’, though it is likely that some 

share underlying pathology with their respective IBS subtypes. 

3.2 Stool patterns 

These vary widely and are the source of some confusion. The 

Rome II classification used a complex multidimensional set of 

criteria which included stool frequency, stool consistency, 

urgency, and straining. Unfortunately these features do not 

correlate well. Thus both straining and urgency can be seen 

with both hard and loose stools, which can also be associated 

with both frequent and infrequent defecation. 12 The Rome III 

subclassification is based solely on stool consistency 11 and is 

hence easier to apply. Patients with hard stools more than 25% 

of the time and loose stools less than 25% of the time are 

defined as ‘‘IBS with constipation’’ (IBS-C) while ‘‘IBS with 

diarrhoea’’ (IBS-D) patients have loose stools more than 25% of 

the time and hard stools less than 25% of the time. About one 

third to one half of IBS patients are ‘‘IBS-mixed’’ (IBS-M), who 

describe both hard and soft stools more than 25% of the time, 

with a small (4%) unclassified (IBS-U), with neither loose nor 

hard stools more than 25% of the time. 12 Those whose bowel 

habit changes from one subtype to another during follow up 

over months and years are termed ‘‘alternators’’ (see 2.3). 

These simple categorisations miss some important details 

about bowel habits. One pattern, familiar to most clinicians but 

rarely studied, is repeated defecation in the morning (morning 

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Box 5 

Alarm features in irritable bowel syndrome 

Age .50 years 

Short history of symptoms 

Documented weight loss 

Nocturnal symptoms 

Male sex 

Family history of colon cancer 

Anaemia 

Rectal bleeding 

N Recent antibiotic use 

rush), when stool consistency changes from an initial formed 

stool to a progressively looser stool as the colonic contents are 

cleared from left to right. This may best be thought of as an 

exaggerated colonic response to the stress of waking and 

starting the day. Regrettably these patterns have not been 

studied in detail and there is no evidence that such features are 

more characteristic of those with stress. Although 60% of IBS 

patients believe that stress aggravates their symptoms, this is 

also true of organic disease in 40%, 19 so this is not helpful 

diagnostically in clinical practice. 

3.3 Food related symptoms 

Many patients believe their symptoms are aggravated by meals 

and in this respect there is considerable overlap with functional 

dyspepsia, which is reported in from 42% to 87% of IBS 

38 81–84 

patients. Thus epigastric pain, nausea, vomiting, weight 

loss, and early satiety are also common. Furthermore, as the 

criteria originally developed by Manning 6 were those that 

distinguished IBS from other gastrointestinal complaints including 

dyspepsia, aggravation by eating was excluded as a symptom 

from the definition. However, when symptoms were systematically 

investigated using a detailed diary, Ragnarsson found 

that, although 50% of patients said that defecation relieved their 

pain, in practice this only occurred within 30 minutes of 

defecation on 10% of occasions, whereas on 50% of occasions 

pain was aggravated within 90 minutes of eating. 85 This may 

represent either symptoms originating in the small intestine or an 

exaggerated colonic response to food, which has been described 

in IBS by some 86 but not all 87 investigators. It may also reflect the 

increased sensitivity to intestinal distension induced by eating, an 

effect particularly obvious after fat ingestion. 88 

3.4 Limitations of the Rome criteria 

Several studies suggest that few clinicians systematically use 

the Rome II criteria 89 but instead tend to rely more on a holistic 

approach which takes note of features beyond the gut. Primary 

care physicians are particularly well placed to make such 

assessments, while specialists, trained to focus solely on 

gastrointestinal symptoms, are in danger of missing these 

important clues. 

3.5 Associated non-gastrointestinal symptoms 

Associated non-gastrointestinal symptoms include lethargy, 

backache, headache, urinary symptoms such as nocturia, 

frequency and urgency of micturition, incomplete bladder 

emptying, and in women, dyspareunia. 90 These are important 

because they can result in patients being referred to other 

specialties, where they may receive inappropriate investigation 

or even treatment (see 2.6). 91 92 Furthermore, there is evidence 

that these symptoms can be used clinically to improve 

diagnostic accuracy. 93 A large study in primary care in the 

United Kingdom suggested that consultation style (see box 4) 

was also predictive of a final diagnosis of IBS. 19 

3.6 Comorbidity with other diseases 

Between 20% and 50% of IBS patients also have fibromyalgia 

94 95 ; conversely IBS is common in several other chronic pain 

disorders, 96 being found in 51% of patients with chronic fatigue 

syndrome, in 64% with temporomandibular joint disorder, and 

in 50% with chronic pelvic pain. 97–99 The lifetime rates of IBS in 

patients with these syndromes are even higher, being 77% in 

fibromyalgia, 92% in chronic fatigue syndrome, and 64% in 

temporomandibular joint disorder. 100 Those with overlap 

syndromes tend to have more severe IBS. 95 IBS patients in 

primary care with numerous other somatic complaints report 

higher levels of mood disorder, health anxiety, neuroticism, 

adverse life events, and reduced quality of life, and increased 

health care seeking. 101 Systematic questioning to identify these 

comorbid disorders is helpful in identifying patients who are 

likely to have severe IBS and associated psychiatric disorder. 

3.7 Psychological features 

At least half the IBS patients can be described as depressed, 

64 96 102–104 

anxious, or hypochondriacal. While previous studies 

suggested that this proportion was increased in secondary and 

tertiary care, more recent large population based surveys 

suggest that even non-consulters have increased psychological 

64 96 103 

distress compared with people who do not have IBS. 

Studies from tertiary care suggest that up to two thirds have a 

psychiatric disorder—most commonly anxiety or depressive 

102 104 105 

disorder. The polysymptomatic nature of IBS suggests 

that hypochondriasis and somatisation 106 may play a role in 

some patients. Recognising this will help, as it should indicate 

that focusing on specific bowel symptoms may not be profitable; 

thus avoiding endless investigation of new symptoms. 

The effectiveness of antidepressants and the response to 

anxiolytic treatment and some psychological treatments also 

argue for an important psychological component to IBS 

symptomatology in some patients. 96 

Symptoms may in many cases be caused by altered cerebral 

interpretation of gastrointestinal symptoms. These often subside 

during sleep. Waking from sleep with pain or diarrhoea is 

usually an indication that other diagnosis should be considered. 

3.8 Alarm features 

While IBS should and can be diagnosed by its characteristic 

features, recognising when a patient does not have IBS is 

equally important. 

Several studies suggest that alarm features (box 5) improve 

the predictive value of the Rome criteria substantially in the 

outpatient setting. 

A follow up observational study lasting 24 months 107 found 

that, in the absence of alarm features and after a full history, 

examination, and investigation, no IBS patients meeting the 

Rome II criteria had another diagnosis. By contrast, a 

substantial number of those not meeting the Rome II criteria 

were left with a final diagnosis of IBS, suggesting that the 

Rome criteria in the absence of alarm symptoms were highly 

specific but not particularly sensitive. A more recent study 

which looked at a range of alarm features found that age over 

50 years at onset of symptoms, male sex, blood mixed in the 

stool, and blood on the toilet paper were all predictors of an 

organic diagnosis. 108 Characteristic features of IBS in this study 

were pain on more than six occasions in the past year, pain that 

radiated outside the abdomen, and pain associated with looser 

bowel movements, all of which were much commoner in IBS 

than in patients with organic disease. 108 Other features 

commoner in IBS than in organic lower gastrointestinal disease 

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included incomplete evacuation, nausea, acid regurgitation, 

bloating, and a history of abdominal pain in childhood, which 

was found in a quarter of subjects. 

Broad spectrum antibiotics lead to transient diarrhoea in 

around 10% of cases, which if severe and persistent should lead 

to consideration of testing for C difficile toxin or sigmoidoscopy 

to exclude pseudomembranous colitis. This recommendation is 

based on expert opinion, as there are no data on the costeffectiveness 

of such an approach. 

3.9 Assessment of severity 

It is characteristic of IBS patients that the pain is reported as 

severe and debilitating and yet there are no abnormal physical 

findings. The patient has not lost weight and may look anxious 

but otherwise well. Several attempts have been made to assess 

109 110 

severity. The functional bowel disorder severity index 

(FBDSI) uses severity of abdominal pain, the diagnosis of 

chronic functional abdominal pain, and the number doctor 

visits in the past six months to calculate an index which 

correlates reasonably well with physician rating of severity. The 

other index, the IBS severity scoring system (IBS SSS), also 

uses a visual analogue scale to measure severity of abdominal 

pain but includes an assessment of pain frequency, bloating, 

dissatisfaction with bowel habit, and interference with life. The 

score obtained with the IBS SSS can assess change over a 

relatively short period and has been used to assess response to 

111 112 

treatment for audit purposes and in clinical trials. The 

patient’s view of severity is important. This is not related to the 

severity of symptoms but is associated with a degree to which 

the symptoms interfere with daily life. 113 

4 MECHANISMS OF IRRITABLE BOWEL SYNDROME 

4.1 Genetics and family learning 

Clinicians have long been aware that a family history of IBS is of 

value in establishing the diagnosis of this condition. 114 IBS clearly 

aggregates within families. First degree relatives of IBS patients 

are twice as likely to have IBS as the relatives of the IBS patient’s 

spouse. 115 Such studies cannot, however, distinguish the influence 

of genetic and shared environmental factors. 

4.1.1 Twin studies 

These assume that monozygotic (MZ) and dizygotic (DZ) twin 

pairs are exposed to the same family environment and therefore 

any greater similarity or concordance between MZ twins is 

caused by genetic influences. Two studies have reported higher 

concordance rates for diagnosed functional bowel disorders 

116 117 

among MZ twins, suggesting a genetic contribution to IBS. 

However, Levy et al noted that among DZ twins, parent/child 

concordance was greater than concordance between the 

twins. 117 As a parent and child share a similar number of genes 

to a pair of DZ twins, this strongly suggests that parent–child 

interactions are more important than genetic influences. A 

recent study of IBS symptoms using the Rome II criteria found 

no difference in concordance rates in MZ and DZ twins, 

suggesting no significant genetic contribution to IBS. 118 In 

summary, twin studies suggest a strong environmental 

contribution to IBS and possibly a minor genetic contribution. 

4.1.2 Parental influences 

Parental reinforcement of illness behaviour and children 

modelling their parent’s behaviour are likely to contribute to 

the development of IBS. Children of IBS patients make more 

health care visits, 119 complain of more gastrointestinal and nongastrointestinal 

symptoms, and have more school absences. 120 

Parental encouragement of the sick role during menstruation or 

colds is associated with more absenteeism and more menstrual 

and non-gynaecological symptoms, respectively. 121 

4.1.3 Candidate genes 

Associations between various candidate genes and IBS have 

been studied. Polymorphisms of the serotonin transporter 5- 

HTT, a adrenergic receptor, interleukin (IL)-10, and tumour 

necrosis factor a (TNFa) genes have been associated with some 

forms of IBS. 122 123 The most intriguing of these studies found 

that 5-HTT polymorphisms were linked to a greater slowing of 

colonic transit in response to the 5-hydroxytryptamine 3 (5- 

HT 3 ) antagonist alosetron. 124 However, published candidate 

gene studies often have small sample sizes and are therefore 

underpowered to detect what is likely to be a small effect. This 

is exacerbated by inadequate stratification for ethnicity and 

122 125 

inherent difficulties in defining phenotype in IBS which 

lead to inconsistent results. 126 Reported associations with 5-HTT 

polymorphisms may plausibly relate not to an association with 

IBS per se but rather to confounding by the recognised 

association of the polymorphisms with anxiety or somatisation. 

127 Somatisation also explains most of the reported familial 

aggregation, 115 is largely genetically determined, 128 129 and may 

be responsible for the genetic contribution to IBS noted in some 

twin studies. 116–118 Interpretation of genetic polymorphism 

studies is also hampered by the frequently poor replication of 

such associations, particularly from small studies. 126 

Familial aggregation of IBS appears from available evidence 

to result largely from environmental influences, such as 

parental–child interactions. Genetic factors may make a minor 

contribution but future studies of this heterogeneous disease 

must establish IBS phenotypes more clearly and in particular 

allow for confounding because of psychological factors. 

4.2 Disturbances of gastrointestinal motility 

Antecedent terms used to describe the clinical entity now 

known as IBS include ‘‘spastic colon’’ and ‘‘irritable colon’’. 

These terms indicate that clinicians of the day thought that this 

condition reflected an underlying motility disorder. This 

perception is further supported by routine prescription of 

antispasmodic agents in the clinical management of IBS 

patients, though as we shall see in section 7, their efficacy is 

limited. 

Although motor disturbances do occur in IBS, these vary 

between patient subtypes 130 and, as around one quarter of IBS 

patients change their bowel habit predominance at least once 

within a year, 14 it is likely that motility patterns may also 

change with time. 

4.2.1 Alterations of gastric motility 

A proportion of IBS patients have delayed gastric emptying, 

particularly of solids. 82 131–135 This appears is especially noticeable 

in patients with constipation 133 or those with overlapping 

dyspeptic symptoms. 82 Disturbed gastric emptying correlates 

highly with a lack of a postprandial increase in electrogastrography 

(EGG) amplitude (r = 0.8; p,0.005). 136 Furthermore, 

emotions such as anger suppress antral contractility in IBS 

patients but increase it in healthy volunteers. 137 

4.2.2 Abnormalities of small bowel motility 

While various abnormalities of small bowel motor activity have 

been demonstrated in IBS under study conditions, none 

appears to be specific for the condition. Small bowel motility 

shows marked diurnal variability and hence consistent results 

can only be obtained with prolonged (at least 24 hour) 

recordings and large numbers of subjects. This may account 

for some inconsistencies in published reports, as many studies 

have been small and of short duration. Small bowel motor 

disturbances reported include: increased frequency and duration 

of discrete cluster contractions, 138–141 increased frequency of 

the migrating motor complex (MMC), 140–142 more retrograde 

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140 143 

duodenal and jejunal contractions, and an exaggerated 

140 142 

motor response to meal ingestion, ileal distension, and 

cholecystokinin (CCK). 142 Corticotrophin releasing hormone 

(CRH) has been reported to increase the number of discrete 

cluster contractions. 144 These observations appear more relevant 

to IBS patients with diarrhoea than with constipation. 139–142 

Small bowel transit is faster in IBS patients with diarrhoea than 

with constipation 145 and, in contrast to healthy controls, colonic 

distension does not appear to reduce duodenal motility in IBS 

patients, suggesting an impaired intestino-intestinal inhibitory 

reflex. 146 

4.2.3 Colonic response to feeding and emotion 

As the predominant symptom in IBS is a change in defecatory 

habit, colonic dysmotility was initially thought to be the likely 

cause. The most consistent motor abnormality recorded in the 

colon is an exaggerated motility response to meal ingestion. 

105 130 147–151 Enhanced colonic motility in response to 

emotional stress, 152 CRH, 144 CCK 151 153 and recto-sigmoid balloon 

distension has also been reported in IBS. 154 However, not all 

studies have reproduced these findings 155–159 and studies under 

151 160–163 

fasting conditions are even more variable. 

Some of this confusion might be explained because earlier 

studies failed to distinguish subtypes of IBS, yet we now know 

that IBS patients with diarrhoea appear to have increased 

colonic motility—particularly the number of high amplitude 

propagating contractions (HAPCs) 151 154 —and accelerated colonic 

transit, while those with constipation have reduced 

145 164 

145 154 165–167 

motility, fewer HAPCs, and delayed transit. The 

significance of bowel habit is further emphasised by the recent 

observations that postprandial platelet-depleted plasma 5-HT 

concentrations—a possible mediator of colonic motility 168 —are 

increased in patients with diarrhoea but reduced in those with 

constipation predominant IBS. 169 Interestingly, postprandial 

distal colonic tone has been shown to be reduced in patients 

with both constipation 170 and diarrhoea 171 172 but not to differ 

significantly from healthy controls under fasting conditions. 173 

4.2.4 Rectal compliance and tension 

Rectal motor physiology has been mainly studied with respect 

to compliance and tension, with some 174–177 but not all 

154 177–182 

studies reporting lower rectal compliance or increased 

tension, or both, in patients with IBS. This has been proposed 

as a possible mechanism for enhanced visceral sensation to 

balloon distension in IBS. 183 

4.2.5 Relation between motor patterns and symptoms 

Whether the above changes in gastrointestinal motility account 

for the symptoms of IBS continues to be debated, but one study 

has shown that over 90% of HAPCs coincide with abdominal 

pain or cramps, while 40% of postprandial HAPCs occurred 

immediately before defecation in IBS patients with diarrhoea. 151 

Small bowel disturbances, such as discrete cluster contractions, 

138 139 141 142 

are also associated with pain, while higher rates of 

duodenal retrograde contractions during phase II of the MMC 

directly correlate with worsening gastrointestinal symptoms in 

IBS patients with diarrhoea. 140 Gastric dysmotility may be 

associated with dyspeptic symptoms in some patients with 

82 184 

IBS, although not all studies have found such a correlation. 

131 

Finally, it must be recalled that many of the phasic motor 

events described above occur in healthy subjects, albeit at a 

lower incidence, and are not associated with concomitant 

symptomatology, suggesting that in IBS heightened visceral 

sensation may also play an important role in the perception of 

these motor events (see 4.3). A comprehensive summary of all 

the above studies on motility in IBS is provided in appendix 1, 

which is available on the journal website (http://www.gutjnl.- 

com/supplemental). 

4.3 Visceral hypersensitivity 

Abdominal pain and discomfort cause considerable morbidity 

in IBS patients and are essential components of the diagnostic 

10 11 

Approximately 

criteria. two thirds of the patients show 

enhanced pain sensitivity to experimental gut stimulation, a 

phenomenon known as visceral hypersensitivity. Visceral 

hypersensitivity is thought to play an important role in the 

development of chronic pain and discomfort in IBS 

185 186 

patients. 

4.3.1 Mechanisms of visceral hypersensitivity 

Both animal and human studies suggest that visceral hypersensitivity 

is caused by a combination of factors that involve 

heightened sensitivity of both the peripheral and the central 

nervous system. Mechanisms that lead to heightened nervous 

system sensitivity have been well described in models of 

inflammation or injury to tissues, and these will be briefly 

outlined. 

4.3.1.1 Peripheral sensitisation 

During tissue injury and inflammation, peripheral nociceptor 

terminals are exposed to a mixture of immune and inflammatory 

mediators such as prostaglandins, leukotrienes, serotonin, 

histamine, cytokines, neurotrophic factors, and reactive meta- 

187 188 

bolites. These inflammatory mediators act on nociceptor 

terminals, leading to the activation of intracellular signalling 

pathways, which in turn upregulate their sensitivity and 

excitability. This phenomenon has been termed peripheral 

sensitisation. Peripheral sensitisation is believed to cause pain 

hypersensitivity at the site of injury or inflammation, also 

known as primary hyperalgesia (increased sensitivity to painful 

stimuli) and allodynia (non-painful stimuli perceived as 

189 190 

painful). 

4.3.1.2 Central sensitisation 

A secondary consequence of peripheral sensitisation is the 

development of an area of hypersensitivity in the surrounding 

uninjured tissue (secondary hyperalgesia/allodynia). This phenomenon 

occurs because of an increase in the excitability and 

receptive fields of spinal neurones and results in recruitment 

and amplification of both non-nociceptive and nociceptive 

inputs from the adjacent healthy tissue. 191 

4.3.2 Evidence of sensitisation in IBS 

Depending on the setting, between 6% and 17% of patients with 

IBS report that their symptoms began with an episode of gut 

inflammation related to gastroenteritis. 192 Furthermore, an 

increase in mucosal T lymphocytes has been reported by several 

investigators in subjects with postinfectious IBS (see 4.5). 

Therefore the environment of nociceptor terminals in the gut of 

IBS patients is likely to be altered, suggesting a role for 

peripheral sensitisation. 

Evidence for central sensitisation as an important mechanism 

for the development of visceral hypersensitivity in IBS 

patients comes from three main observations. First, in response 

to colonic stimulation, patients with IBS have greater radiation 

of pain to somatic structures in comparison with healthy 

subjects. 193 Second, some IBS patients also suffer from 

fibromyalgia, a condition characterised by somatic hyperalgesia. 

194 Finally, patients with IBS also often show hypersensitivity 

of more proximal regions of the gut. 186 These observations 

may be explained by the fact that the innervation of different 

gut organs overlaps and converges with that of the somatic 

structures at the level of the spinal cord. Therefore the 

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sensitisation of proximal organs in IBS patients, and greater 

radiation of pain to somatic structures in response to visceral 

stimulation in patients who also have fibromyalgia, could all be 

explained by the phenomenon of central sensitisation of the 

spinal segments that demonstrate this viscero-visceral and 

viscero-somatic convergence. 

4.3.3 Central pain processing 

Peripheral and central sensitisation are by no means the only 

mechanisms that can explain the development of visceral 

hypersensitivity observed in IBS patients. This is because the 

perception of pain in humans involves processing of sensory 

inputs in various cortical and subcortical brain structures. Our 

understanding of the brain processing of visceral sensation has 

improved significantly because of the availability of functional 

brain imaging techniques such as cortical evoked potentials, 

magnetoencephalography, functional magnetic resonance imaging 

(fMRI), and positron emission tomography (PET). 

These functional brain imaging studies have shown that, like 

somatic sensation, visceral sensation is represented in both the 

primary (S1) and the secondary somatosensory cortex (S2), and 

this representation most probably mediates the sensory 

discriminative aspects of sensation. Furthermore, visceral 

sensation is also represented in the paralimbic and limbic 

structures such as the anterior insula, anterior cingulate, and 

195 196 

prefrontal cortices. These areas are likely to mediate the 

affective and cognitive components of visceral sensation. 

Activation of subcortical regions such as the thalamus and 

periaqueductal grey matter in response to rectal stimulation has 

also been demonstrated. 196 

4.3.4 Descending and spinal modulation of pain 

processing 

Animal studies have shown that stimulation of the periaqueductal 

grey matter in the midbrain inhibits behavioural 

responses to noxious stimulation because of inhibition of 

spinal neurones. 197 The periaqueductal grey matter receives 

direct inputs from the hypothalamus and the limbic cortex and 

controls spinal nociceptive transmission through descending 

pathways. These selectively target the dorsal horn laminae that 

house the nociceptive relay neurones. This circuit can therefore 

selectively modulate nociceptive transmission by its anatomical 

proximity to central ends of the primary afferent nociceptor 

terminals and dorsal horn neurones that respond to noxious 

stimulation. 

Furthermore, some neurones in the dorsal horn of the spinal 

cord are strongly inhibited when a nociceptive stimulus is 

applied to any part of the body, distinct from their excitatory 

receptive fields. This phenomenon is termed diffuse noxious 

inhibitory control (DNIC) 198 and refers to a neurophysiological 

mechanism that underlies the long established clinical phenomenon 

of counterirritation, in which application of an acute 

aversive stimulus provides temporary relief of chronic and 

recurrent pain. 199 Several animal and human studies have 

assessed the role of spinal nociceptive processes using DNIC 

paradigms and have demonstrated hyperexcitability of spinal 

nociceptive processes in a subgroup of IBS patients associated 

with failure of descending inhibitory control. 200 

4.3.5 Altered central processing 

Brain imaging studies have begun to address the possible 

neural mechanisms of hypersensitivity in IBS patients, and a 

common finding has been that, compared with healthy 

controls, patients with IBS show altered or enhanced activation 

of regions involved in pain processing, such as the anterior 

cingulate cortex, thalamus, insula, and prefrontal cortex, in 

response to experimental rectal pain. 201–203 However, variable 

activation patterns in IBS patients have been reported, and the 

role of these functional brain imaging studies is not clearly 

established in helping us to understand the mechanism of 

visceral hypersensitivity in IBS patients. 204 The main reason for 

this is that most of the functional brain imaging techniques 

used so far in assessing the brain processing of visceral 

sensation in IBS patients have relied on techniques such as 

fMRI and PET. These techniques image minute changes in 

cortical blood flow in response to a stimulus and, because of the 

very small effects being measured, require group studies to 

detect significant differences. As visceral hypersensitivity in IBS 

patients may be caused by a variety of mechanisms, unless the 

groups under study consist of a very homogeneous population 

with similar mechanisms, significant differences are hard to 

detect. In contrast, studies using neurophysiological techniques 

such as cortical evoked potentials and magnetoencephalography 

rely on identifying electromagnetic fields generated in 

response to a peripheral stimulus and can be used to study 

individual patients. Recently, cortical evoked potentials have 

been used in non-cardiac chest pain patients and the results 

suggest that it may be possible to differentiate visceral 

hypersensitivity caused by sensitisation of afferent nerves from 

that caused by psychological influences. 205 

4.3.6 Summary 

Patients with IBS characteristically complain of abdominal 

pain. A proportion of these patients display heightened pain 

sensitivity to experimental gut stimulation (visceral hypersensitivity). 

Chronic pain in these patients can occur through 

various central and peripheral mechanisms. The challenge for 

the future is to be able to differentiate between these 

mechanisms so that patients can be treated more specifically. 

4.4 Stress response 

4.4.1 The hypothalamo-pituitary-adrenal axis 

The response of an organism to external stressors is mediated 

through the integration of the hypothalamo-pituitary-adrenal 

(HPA) axis and the sympathetic branch of the autonomic 

nervous system with the host immune system. 206 A potential 

novel aetiopathological model for IBS combines the classical 

observation of high levels of anxiety in IBS patients and the 

demographic similarity between patients with IBS and other 

functional disorders (such as fibromyalgia and chronic fatigue 

syndrome). The model proposes altered central stress circuits, 

in predisposed individuals, which are triggered by external 

stressors resulting in the development of gut and extraintestinal 

symptoms. The HPA axis is part of that circuit: in the 

hypothalamus, paraventricular nucleus neurones release corticotropin 

releasing factor (CRF), which stimulates anterior 

pituitary secretion of adrenocorticotropin hormone (ACTH). 

This in turn acts on the adrenal medulla, resulting in cortisol 

secretion into the circulation. Release of CRF is dependent on 

input from the limbic structures in the brain and from 

peripheral feedback by ACTH and cortisol. The production 

and release of CRF is therefore under multiple control systems, 

reflecting the pluripotent role of this peptide in controlling 

autonomic, immunological, and emotional responses to 

stress. 207 Circulating peripheral levels of CRF do not reflect 

levels released into the hypophyseal circulation, so HPA axis 

activity is traditionally assessed by ACTH and cortisol measurements. 

4.4.2 Neuroimmune interactions 

The emerging recognition that a distinct subgroup of IBS 

patients develops postinfectious IBS has led to the speculation 

that altered HPA axis activity may be causally involved in 

generating symptoms. The persistence of chronic inflammatory 

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mucosal changes and enterochromaffin cell hyperplasia that 

persists after eradication of the infectious organism 208 are 

consistent with an inadequate physiological response to acute 

gut inflammation, in particular an inadequate cortisol or 

altered sympathetic response. The key interplay between the 

autonomic nervous system and the HPA axis in regulating gut 

mucosal immunology has led to a rapidly emerging body of 

work looking at how the stress response, which activates both 

these effector systems, may be aetiologically important in IBS. 

The stress response may thus be of central pathophysiological 

importance in uniting the sensory, motor, immunological, and 

possibly even genetic abnormalities that have been observed in 

IBS. Epidemiological observations have pointed to the importance 

of environmental stressors both in predisposing towards 

developing IBS and in perpetuating the symptoms of IBS. 

Previous life stressors 209–211 and past exposure to childhood 

abuse 212 predispose to the risk of developing IBS in later life. 

Psychiatric illness episodes or anxiety-provoking situations 

preceded the onset of bowel symptoms in two thirds of IBS 

patients attending outpatients, 213 and IBS patients report 

significantly more negative life events than matched peptic 

ulcer patients. 210 Additionally, psychological traits such as 

hypochondriasis, 214 anxiety, and depression predispose previously 

healthy individuals who develop gastroenteritis to 

developing symptoms of IBS. 215 

4.4.3 Abnormalities of emotional motor system 

Allied to the evidence from animal experiments, clinical 

observations, and brain imaging studies, these epidemiological 

data have led to the development of the notion of a central 

‘‘emotional motor system’’. 216 The outputs from this system 

probably involve the HPA, which is the key endocrine stress 

system in humans. 217 218 The inputs to this system involve both 

altered visceral sensory input 178 219 and altered visceral perception. 

220 221 It is likely that the autonomic nervous system is of 

prime importance to these input and output circuits, given its 

neuroanatomical and neurophysiological connections, and 

there is increasing evidence of autonomic dysfunction in 

IBS. 144 222 223 In terms of motor change, diarrhoea predominant 

IBS seems to be associated with sympathetic adrenergic 

dysfunction while constipation predominant IBS seems to be 

224 225 

associated with parasympathetic dysfunction. 

Approximately three quarters of patients report that stress 

leads to acute abdominal pain and changes in stool pattern. 21 In 

terms of sensory change, recent evidence has pointed to a 

dissociation between visceral sensitivity and autonomic function 

in IBS patients in response to acute physical and 

psychological stress. 223 This would suggest involvement of a 

different regulatory mechanism (either central or peripheral) in 

IBS patients in response to stress. That this mechanism may be 

endocrine is suggested by the finding that a subgroup of IBS 

patients has an exaggerated endocrine stress response, as 

shown by a heightened release of ACTH and cortisol in response 

to exogenous CRF administration. 217 226 This exaggerated stress 

HPA response seems to be associated with mucosal immune 

activation. 226 

4.4.4 Imaging the stress response 

An additional way to study the stress response in IBS has been 

to employ functional brain imaging techniques. The ventral 

portion of the anterior cingulate cortex and, to a lesser extent, 

the medial prefrontal cortex have repeatedly been shown to be 

differentially activated by rectal balloon distension in IBS 

patients compared with controls. 196 This activation is heightened 

by acute stress. 227 Taken together with established 

neuroanatomical knowledge, it has been proposed that the 

response to acute stress is coordinated by the amygdala, locus 

coeruleus, and hypothalamus. 228 These structures are closely 

interconnected and it is suggested that the amygdala processes 

the emotional component of the response to stress, the locus 

coeruleus the autonomic response, and the hypothalamus the 

endocrine response. 227 

4.4.5 Implications for treatment 

This ever increasing understanding offers the potential for 

manipulating the stress response to provide novel treatments 

for IBS. Potential mechanisms include non-specific approaches, 

such as with tricyclic antidepressants, 227 or the use of selective 

compounds, such as the CRF antagonists. The potential for 

these latter drugs is enormous, given the core role of CRF in 

modulating the stress response. 229 

4.5 Postinfective IBS 

A small subgroup of IBS patients relate the onset of their 

symptoms to a bout of infectious gastroenteritis and these have 

proved a useful model in helping to understand other nonpostinfectious 

types of IBS. The prevalence of postinfective IBS 

varies from 17% in primary care in the United Kingdom to as 

little as 6% in tertiary care in the USA. 192 Population surveys 

indicate a relative risk of 11.1 230 to 11.9 231 of developing IBS in 

the year following a bout of gastroenteritis. Such IBS patients 

are an attractive group in whom to study the mechanisms 

underlying IBS as they represent ‘‘nature’s experiment’’, with 

less confounding by psychological factors and a clearly defined 

start date. 

4.5.1 Risk factors 

Known risk factors in order of importance include the severity 

of the initial illness, bacterial toxigenicity, 232 female sex, a range 

of adverse psychological factors including neuroticism, hypochondriasis, 

233 anxiety, and depression, 215 and adverse life 

events 214 (for a review see Spiller 208 ). Postinfective IBS has been 

reported after shigella, 234 salmonella, 235 236 and campylobacter 215 

infections and does not appear specific to any particular 

organism. 237 

4.5.2 Mucosal abnormalities 

Histological studies indicate that postinfective IBS is characterised 

by increased lymphocyte numbers in mucosal biopsies, 

215 234 an effect which is seen throughout the colon. 234 Where 

the terminal ileum has been biopsied, increased mast cells have 

also been noted. 234 Another change following inflammation is 

enterochromaffin cell hyperplasia, a feature which, as animal 

models demonstrate, is dependent on functioning T cells. 238 

While in most subjects this change resolves over the ensuing 

three months, in postinfective IBS levels of both lymphocytes 

and enteroendocrine cells remain raised. 215 Failure of resolution 

of inflammation has also been documented in several studies 

showing persistent elevation of interleukin-1b mRNA expression, 

implying impairment of downregulation of inflammation. 

234 239 Increased enterochromaffin cell numbers are 

associated with an increase in postprandial 5-HT release, an 

abnormality shown both in postinfective IBS 240 and in 

diarrhoea predominant IBS without an obvious postinfective 

origin. 169 Immediately after gastroenteritis affecting the small 

bowel there may be transient lactose intolerance which is 

particularly obvious in young children. However, in adults with 

postinfective IBS, who by definition have had symptoms for 

over six months, the incidence of lactose malabsorption is no 

different from uninfected controls. 241 

4.5.3 Gut permeability 

Another abnormality found in most individuals suffering from 

bacterial gastroenteritis is increased gut permeability. 242 

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Moreover, persistently increased gut permeability is seen in 

those who develop postinfective IBS, as was reported in the 

Walkerton health study. 243 In that study of 105 new cases of IBS 

following infection with E coli and Campylobacter jejuni, a 

lactulose/mannitol ratio of .0.02 was seen in 35% of IBS cases 

compared with just 13% of non-IBS controls. 243 This increased 

permeability, which would allow access of bacterial products to 

the lamina propria, could be a mechanism for perpetuating 

chronic inflammation. 

4.5.4 Neuroimmune mechanisms 

As stress and mucosal abnormalities are known to interact and 

214 215 

contribute equally to the development of postinfective IBS, 

it is possible that stress, by activating mast cells, may contribute 

to persistently increased gut permeability and hence to immune 

activation. This stress effect has been demonstrated in 

244 245 

numerous animal models. Recent studies suggest that, 

regardless of bowel habit subtype, IBS patients may show 

evidence of an ongoing immune activation. 246 A genetic 

tendency to underproduce IL-10 might pre-dispose to this, as 

an abnormally small number of high IL-10 producing genotypes 

has been reported in IBS 247 (though a recent smaller study has 

failed to confirm this 248 ). 

4.6 Bloating 

Abdominal bloating is reported by up to 96% of patients with 

IBS, is more common in female patients, and is often ranked as 

their most bothersome symptom. 249 However, its presence in 

other functional disorders—such as functional dyspepsia and 

chronic constipation, and indeed even in healthy subjects— 

means that it is not considered a diagnostic criterion but a 

supportive symptom of IBS. 11 Sufferers typically report a 

worsening of bloating as the day progresses, particularly after 

meals, with the symptom usually improving or disappearing 

overnight, which helps to distinguish if from more sinister 

causes of abdominal swelling such as ascites or an ovarian 

cyst. 250 251 This increase in the sensation of bloating may or may 

not be associated with an increase in abdominal girth (that is, 

distension), which if present can reach 12 cm. 251 Distension 

only correlates with bloating in IBS-C patients, who suffer from 

this more frequently (60%) than those with IBS-D (40%). 251 

Men do not appear to complain of bloating or distension as 

often as women, although this may partly reflect the fact that 

they often describe the symptom in different language, 

referring to it as ‘‘tightness’’ or ‘‘hardness’’ of the abdomen. 

4.6.1 Mechanisms 

While many patients attribute their bloating to ‘‘trapped wind’’, 

studies have generally failed to show excessive intra-abdominal 

249 252–254 

gas. Indeed in studies where 10 times the normal 

amount of gas present in the gut was infused into the intestine, 

it resulted in less than half the mean increase in abdominal 

distension seen in IBS (that is, ,2 cm). 252 Thus abnormal gas 

volume cannot be the sole cause of distension and bloating, 

although there is evidence of impaired gas transit in these 

252 255 256 

patients. The observation that bloating only strongly 

correlates with distension in patients with IBS-C 251 suggests 

that the pathophysiology is likely to be multifactorial and may 

differ between the bowel habit subtypes. Indeed there is 

evidence that small bowel transit 257 may be delayed in IBS 

patients with bloating and subjective reports of distension. This 

is supported by recent objective measures of girth using the 

validated technique of abdominal inductance plethysmography, 

258 259 which showed that IBS-C patients with delayed large 

bowel transit distended significantly more than IBS-C patients 

with normal transit. 260 Using this technique it has also been 

shown that, compared with healthy subjects, patients with 

bloating alone have lower sensory thresholds, whereas those 

with bloating and distension have normal or slightly higher 

sensory thresholds. 261 Thus bloating alone—which tends to be 

commoner in IBS-D—may be more of a sensory problem, 

whereas bloating with distension—which tends to be commoner 

in IBS-C—may be more of a mechanical problem. 

However, computed tomography of the abdomen in distended 

IBS patients has shown that distension is not caused by 

voluntary protrusion of the abdomen or exaggerated lumbar 

lordosis. 254 Moreover, electromyographic assessment of the 

anterior abdominal musculature in distended and healthy 

subjects revealed no differences. 262 However, rectal infusion of 

gas was shown to be associated with paradoxical relaxation of 

the internal oblique muscle in patients with distension 

compared with an increase seen in healthy volunteers, 263 

suggesting an abnormality in an abdominal accommodation 

reflex irrespective of its strength. 

5 CLINICAL HISTORY AND INVESTIGATION 

Appropriate management is highly dependent on the information 

obtained at the time of the initial consultation and in 

almost all cases the diagnosis of IBS can be made on the basis 

of clinical history alone, integrating the many features listed 

below to come to a final conclusion. 

5.1 History of symptoms 

The patient should be allowed to tell their story in their own 

words to ensure that they feel the doctor has understood their 

concerns, as previous consultations may have been unsatisfactory 

in this respect. The clinician should make an effort to 

understand the psychosocial factors which might have led the 

patient to seek help at this particular time. Modern medical 

education emphasises the benefits of optimal consultation 

techniques designed to elicit a therapeutic alliance between 

patient and physician. These include optimal eye contact, body 

language which conveys empathy, and open ended questioning 

designed to elicit the patient’s ideas and thus ensure their 

concerns and expectations are met. While much of this is based 

on cultural expectations, there is some evidence that such 

practice can reduce reconsultation rates. 264 Approximately half 

the consulting patients believe they have serious disease such 

as cancer. 265 Disease or death in close relatives is a frequent 

cause of health anxieties, and understanding the patient’s 

concerns will make it much easier to reassure them and to 

achieve a satisfactory consultation. It may then be appropriate 

to make a more specific inquiry about the chronology of key 

symptoms and possible precipitating factors such as gastroenteritis. 

5.1.1 Features of pain 

Key symptoms include the pattern of pain or discomfort, the 

nature of the associated bowel disturbance, and abnormalities 

of defecation. Pain relieved by defecation or associated with 

changes in stool consistency or frequency is usually intestinal in 

origin. Pain without these associations should lead to careful 

consideration of other conditions including neoplasms and 

inflammatory bowel, urogenital, or musculoskeletal diseases. 

5.1.2 Constant pain 

Constant unrelieved pain may reflect neoplastic pain or be due 

to functional abdominal pain syndrome. 80 This is a particularly 

difficult syndrome to manage, commonly associated with 

complex psychiatric problems including possible personality 

disorder. 

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5.1.3 Disordered bowel habit 

Clarification of exactly what the patient means by the terms 

‘‘diarrhoea’’ and ‘‘constipation’’ is vital, and the Bristol stool 

form score is an easy way to do this without misunderstanding. 

266 It should be recognised that the patient may experience 

both loose and hard stools within a short period, and around 

half fit the category of ‘‘mixed’’ bowel habit rather than either 

‘‘diarrhoea’’ or ‘‘constipation’’. 11 

Other features that may trouble the patient are bloating (see 

4.6), straining, incomplete evacuation, passage of mucus per 

rectum, urgency, and sometimes incontinence. In addition to 

inquiring about individual symptoms, their severity should be 

ascertained, as different patients rank different symptoms— 

including extracolonic features—as the most intrusive aspect of 

their problem. The recognition of the association of extracolonic 

symptoms with IBS is important as already discussed (see 3.5), 

as this can avoid unnecessary investigation as well as 

inappropriate referral to other specialties. Patients are often 

relieved to know about the association of these features with 

IBS, as they frequently feel that underlying pathology is being 

overlooked. Indeed it may be helpful to point out that having 

multiple somatic complaints makes it more likely that they 

have a ‘‘functional’’ rather than an ‘‘organic’’ disorder. 

5.2 Psychological factors 

Approximately two thirds of IBS patients referred to secondary 

care show some form of psychological distress, most commonly 

anxiety. This may not necessarily be easily recognised, as some 

patients are reluctant to expose their feelings, whereas normal 

anxiety about unexplained symptoms may be mistakenly 

judged as abnormal. Hostility may be apparent, particularly in 

patients who feel dissatisfied with previous consultations with 

doctors, whom they felt expressed little sympathy. It is vital 

that any ongoing severe stress, especially of a domestic nature, 

is identified, as it has been shown this impairs the response to 

treatment. 77 Multiple unexplained physical symptoms are 

common in IBS 19 and can be a manifestation of somatisation 

disorder. This complicates the interpretation of symptoms and 

response to treatment in IBS (see 5.8.2). 

5.3 Family history 

It is also important to inquire about a family history of 

inflammatory bowel disease or colon cancer, particularly below 

the age of 50, as this will influence patients’ concerns and 

expectations and should correctly lower the threshold for 

investigation. 

5.4 Dietary considerations 

Almost all patients with IBS will have tried some form of 

dietary manipulation and in some instances this can lead to the 

adoption of bizarre diets that may be nutritionally inadequate. 

It should be remembered that favourite foods or foods that are 

taken regularly without the chance of observing the effects of 

withdrawal are more likely to be causing trouble, so a careful 

history is worthwhile to identify ingestion of abnormal 

amounts of fruit, caffeine, dairy products, and dietary fibre, 

particularly bran. It has been shown that a tendency to an 

eating disorder is quite common in female IBS patients and the 

two conditions can therefore exacerbate each other (the role of 

dietary manipulations is dealt with in section 7.1). 

5.5 Precipitating and exacerbating factors 

A small proportion of patients, varying from 17% in primary 

care in the United Kingdom to 6% in a university outpatient 

clinic in the USA, 192 will date their IBS to an episode of 

gastroenteritis or ‘‘food poisoning’’. Other events that might 

cause problems, even in normal individuals, tend to cause an 

exaggerated response in IBS. Thus menstruation or the 

administration of drugs such as antibiotics, 267 non-steroidal 

anti-inflammatory drugs (NSAIDs), or statins may exacerbate 

symptoms. IBS symptoms can also be exacerbated by stress. 

Smoking or alcohol in moderation do not seem to affect the 

course of IBS. If an analgesic is required, paracetamol is 

preferred to opiates or NSAIDs as it is less likely to disturb 

bowel function. 

5.6 Physical examination 

Physical examination usually reveals no relevant abnormality. 

General examination for signs of systemic disease should be 

followed by abdominal examination. This includes asking the 

patient to demonstrate the area of pain. Note should be made of 

whether pain is diffuse (expressed by an outstretched hand) or 

localised (pointing with a finger). Visceral pain is poorly 

localised, so pain which is well localised is atypical and should 

suggest possible alternative diagnoses. Abdominal wall pain 

originating from hernia, local muscle injury, or trapped nerves 

can be readily identified by Carnett’s test. This involves asking 

the patient to fold their arms across their chest and raise their 

head off the pillow against gentle resistance from the 

physician’s hand. Exacerbation of the pain is a positive 

Carnett’s test. A recent study showed that abdominal wall pain 

is a secure diagnosis which rarely needs to be revised. 268 Pain 

localised to the rib cage can also be a source of confusion. The 

painful rib syndrome, characterised by point tenderness and 

pain on springing the rib cage, has a benign course and its 

269 270 

recognition can save much unnecessary and futile testing. 

Examination of the perianal region and rectum will be 

appropriate in most cases, especially those with diarrhoea, 

rectal bleeding, or disordered defecation. Those with rectal 

bleeding or diarrhoea should also have an endoscopic examination 

to exclude local pathology including colitis, haemorrhoids, 

or rectal cancer. This can either be a limited sigmoidoscopy in 

the clinic or as a planned procedure soon after. Those with a 

family history of colorectal cancer or those over 50 with recent 

onset of symptoms (less than six months), including a change 

in bowel habit, should also be considered for colonoscopy (see 

5.8.3). 

5.7 Alarm features (see box 5) 

Rectal bleeding, anaemia, weight loss, nocturnal symptoms, a 

family history of colon cancer, abnormal physical examination, 

recent antibiotic use, age of onset more than 50 years, and a 

short history of symptoms should all lead to careful evaluation 

before a diagnosis of IBS is made 108 271 because of the possibility 

of an inflammatory or neoplastic cause. However, it should be 

recognised that minor bleeding from the anus, usually 

combined with anal discomfort, is extremely common and 

should not exclude an IBS diagnosis, even though an 

examination may be needed to reassure the patient and 

clinician. The Association of Coloproctologists of Great Britain 

and Ireland guidelines on management of colorectal cancer 

recommend that rectal bleeding combined with a change in 

bowel habit and in the absence of anal symptoms should be 

fully investigated, as a significant number will have colorectal 

cancer (www.acpgbi.org.uk/download/GUIDELINES-bowelcancer.pdf). 

A large recent study in an unselected gastroenterology 

outpatient clinic in Australia indicated that age over 50 years 

and rectal bleeding of any type were significantly commoner in 

those with a final diagnosis of organic disease, and should 

therefore lead to full evaluation before a final diagnosis of IBS 

is made (see 5.6). 108 

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5.8 Investigations 

5.8.1 Initial laboratory investigations 

The concept that IBS is a diagnosis of exclusion is no longer 

tenable and in a straightforward case of IBS in a young person, 

investigations—particularly those involving irradiation— 

should be kept to a minimum. The yield in those with 

established IBS is low but not zero. 272 The patients should be 

warned therefore from the outset that investigations are likely 

to be normal, thus avoiding the possibility that negative results 

will lead to the demand for ever more invasive and unnecessary 

tests. A full blood count (FBC) should be ordered in all older 

patients at first presentation, and an FBC plus erythrocyte 

sedimentation rate (ESR) and C reactive protein in all those 

with recent onset D-IBS. Endomysial or tissue transglutaminase 

antibodies show high sensitivity and specificity in 

distinguishing patients with coeliac disease from healthy 

controls, but in IBS—where the incidence is low (0– 

3%) 273 274 —sensitivity is lower at 79%, with a specificity of 

98%. 274 However, many clinicians working in areas of high 

incidence such as the United Kingdom undertake these tests 

because the diagnosis of coeliac disease radically alters 

treatment over a lifetime and may otherwise easily be missed. 

It should be emphasised that this section deals with IBS and 

not painless diarrhoea, for which there are separate guidelines 

(see guidelines for the investigation of chronic diarrhoea on the 

BSG website at http://www.bsg.org.uk). 

5.8.2 Psychological investigation 

Given the frequency of anxiety and depression it is useful to 

assess these features objectively. The hospital anxiety and 

depression scale (HADS) is a simple 14 item questionnaire that 

can be used even in a busy outpatient clinic to provide an 

objective measure of anxiety and depression. The 15 item 

patient health questionnaire (PHQ 15) 275 may also be helpful in 

difficult cases, as it clearly identifies the presence of multiple 

somatic symptoms (somatisation) which may otherwise be 

missed in a busy consultation. While there are no randomised 

studies showing benefit, there are several studies showing that 

somatisation is common in IBS outpatients, 276 correlates with 

impaired quality of life, 276 and predicts dissatisfaction 106 with 

treatment and increased health care use (see 7.2.2). 

5.8.3 Second level investigations including endoscopy 

and imaging 

Second level investigations are based on the likely differential 

diagnosis (box 6). Given the high frequency of colonic cancer in 

the population at large, an examination of the colon is 

advisable for a change in bowel habit over the age of 50 

(earlier if there is a first degree relative affected by colorectal 

cancer when aged less than 45 years, or two affected first 

Box 6 

Differential diagnosis of diarrhoea predominant 

irritable bowel syndrome 

Microscopic colitis 

Coeliac disease 

Giardiasis 

Lactose malabsorption 

Tropical sprue 

Small bowel bacterial overgrowth 

Bile salt malabsorption 

N Colon cancer 

degree relatives 277 ). As IBS patients have no increased risk of 

colon cancer, advice on screening for this is no different from 

the general population. 

Patients with IBS-D tend to require more in the way of 

investigation than IBS-C, because of the overlap with other 

diarrhoeal diseases including coeliac and inflammatory bowel 

disease. It needs to be recalled that microscopic colitis now 

accounts for 20% of unexplained diarrhoea in the over 70s age 

group in countries where colonoscopy is freely available. 278 Tests 

for malabsorption or small bowel bacterial overgrowth are not 

undertaken in straightforward cases of IBS but those with 

difficult diarrhoea—particularly if associated with defecation 

which disturbs sleep—may warrant further tests (see guidelines 

for the investigation of chronic diarrhoea on the BSG 

website at http://www.bsg.org.uk). Giardiasis should be 

excluded by stool examination or duodenal biopsy in those 

with acute onset of diarrhoea as symptoms can be long lasting. 

Adult acquired lactose intolerance, which can be identified by a 

lactose breath hydrogen test, can cause IBS-type symptoms and 

should be considered, especially in racial groups with a high 

incidence of this feature, which worldwide is the norm rather 

than the exception. 279 A simple screen for this is to ask the 

patient to undertake a ‘‘milk challenge’’ of one pint of skimmed 

milk which contains approximately 25 g of lactose. If no 

symptoms result then lactose intolerance is unlikely. A positive 

result should be followed by objective confirmation using a 

formal lactose breath hydrogen test, as the milk challenge lacks 

specificity. It should be noted that these recommendations are 

based on expert opinion and experience as there are no 

published data. 

Sudden onset of severe diarrhoea, especially if it is of large 

volume with nocturnal disturbance, should suggest bile acid 

malabsorption, which can be diagnosed by the SeCHAT test. 280 

It should be noted that only those with severe malabsorption 

(less than 5% of labelled bile acid retained at seven days) 

respond predictably to cholestyramine. 281 Constant upper 

abdominal pain, particularly if it radiates to the back, should 

lead one to consider pancreatic disease, best investigated by 

means of abdominal spiral computed tomography. Right upper 

quadrant pain with biliary features may indicate the need for 

ultrasound investigation and, rarely, consideration of sphincter 

of Oddi dysfunction, especially if pain is associated with a rise 

in liver enzymes or amylase. 282 These investigations should be 

restricted to those with typical meal provoked symptoms, as IBS 

patients with asymptomatic gall stones are in danger of being 

subjected to an unnecessary cholecystectomy without benefit to 

their pain. 

Table 2 Summary of the recommendations for 

investigating irritable bowel syndrome 

Intervention 

Quality of Benefit/ Strength of 

evidence harm recommendation 

N Take a symptom history Low Net benefit Definitive 

N Assess psychosocial factors Low Net benefit Definitive 

N Physical examination Low Net benefit Definitive 

N Check for alarm symptoms Moderate Net benefit Definitive 

N Investigations 

FBC Moderate Net benefit Definitive 

EMA Moderate Trade-offs Qualified 

Lactose breath hydrogen 

test 

Moderate Net benefit Qualified 

Colonoscopy Moderate Trade-offs Qualified 

Abdominal ultrasound Low Trade-offs Qualified 

EMA, endomysial antibodies; FBC, full blood count. 

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5.9 Recommendations 

A summary of the recommendations for investigating IBS is 

given in table 2. 

6 DIAGNOSIS AND INITIAL MANAGEMENT OF IBS IN 

PRIMARY CARE 

Adult patients who present to their general practitioner with 

lower gastrointestinal tract disorders often pose a difficult 

diagnostic problem. They account for one in 20 of all general 

practice consultations 19 and yet their symptoms are frequently 

ill defined. Although functional disorders such as IBS are the 

most prevalent, the possibility of colorectal cancer or inflammatory 

bowel disease may create diagnostic uncertainty and 

reluctance on the part of the doctor to attribute the symptoms 

to a specific diagnosis. 283 

6.1 Differences between primary and secondary care 

Primary care differs from specialist care because the general 

practitioner’s greater familiarity with the patient, and their 

previous consultations and behaviours, enable current complaints 

to be seen in context rather than in isolation. 

Furthermore, it involves the first contact for care of problems 

and diseases at a stage when they are likely to be poorly 

differentiated. Lastly, it is characterised by a model of patient 

care that is longitudinal and comprehensive, and takes account 

of the biopsychosocial context of the person’s problem. 

These characteristics become particularly important when 

considering chronic disorders, such as IBS, where patients place 

high priority on continuity of care 19 and where the doctor’s 

relationship with the patient can be therapeutic in itself. Time is 

frequently used as both a diagnostic and a therapeutic tool in 

primary care. 

6.1.1 Diagnosis in primary care 

Existing diagnostic criteria for IBS are based on specific 

symptoms of defined duration and frequency and have been 

derived from the characteristics of patients in secondary care. 

Their applicability to clinical practice has been challenged as 

unnecessarily restrictive, 32 with one study finding that only a 

minority of those diagnosed with IBS in primary care fulfilled 

the Rome II criteria. 35 This may be because their restrictive 

approach is at odds with the diagnostic process used in primary 

care. Here the diagnosis is based on risk estimations that start 

from the prevalence of symptoms in primary care, balancing the 

perceived relative risks of serious (notably cancer) and nonserious 

disease, and combining this with a limited number of 

investigations. In this diagnostic process, symptoms, history, 

psychosocial background, disease patterns, previous disease 

history, and consultation behaviour play important roles. At the 

same time, the patient’s ideas, concerns (notably about cancer, 

see 5.1), and expectations are also addressed. 

6.1.2 Diagnostic decision making in primary care 

GPs (primary care physicians) tend to make a positive diagnosis 

of IBS when the risk profile for that condition is high, the 

characteristics of the patient fit the profile for functional 

disease, and the risk of serious bowel disease is low. 284 This 

profiling approach to diagnosis is quite distinct from a criterion 

based approach, though its key features and their relative 

importance are unknown. Most surveys suggest that similar 

strategies are used in secondary care, as very few specialists use 

formal diagnostic criteria for IBS. 

6.1.3 Diagnosing IBS in primary care 

In a rigorous consensus development exercise using a nominal 

group technique, 285 European GPs identified alteration in bowel 

habit and bloating or distension, with symptom-free intervals, 

as characteristics essential for the diagnosis of IBS. 286 

Abdominal pain per se was not an essential characteristic, 

though participants described as essential a feature of 

‘‘disordered abdominal sensation’’, which included pain, 

discomfort, and annoyance. This reflected differences in 

expression according to culture and language. Symptom 

characteristics and interrelationships—such as relief of abdominal 

pain/discomfort/annoyance with defecation—were considered 

supportive of the diagnosis. Measures of frequency and 

persistence of symptoms were considered relevant but without 

consensus on specific figures. 286 

Consultation style, notably frequent consultation, somatisation, 

and abnormal illness behaviours in response to stress are 

key contextual features supporting the diagnosis of IBS in 

general practice. Inappropriate consultations for minor illness 

and multiple somatic complaints have been described for IBS 

by Whitehead and Bosmajian. 287 

Extracolonic symptoms, however, have less prominence in 

making the diagnosis, and in most instances there was no 

consensus on their significance among GPs. Apart from being 

associated with IBS, symptoms such as tiredness, urinary 

frequency, and backache are commonly encountered in general 

practice and may be perceived as lacking specificity, while 

others such as history of abuse lack sensitivity 

Mood assessment can be done rapidly using three questions 

288 (box 7). In general practice the diagnosis of depression 

after these three questions have been answered has a sensitivity 

of 79% and a specificity of 94%. 288 

6.1.4 Investigations in primary care 

The consensus group considered only a limited number of 

investigations to be essential for the diagnosis of IBS. Rectal 

examination confirms the consistency of the stool and 

identifies anal conditions and low rectal masses, but has a 

low sensitivity as a diagnostic test for rectal cancer. 289 A full 

blood count should be ordered in all older patients at first 

presentation and an FBC and ESR/CRP in all those with new 

IBS-D. Faecal occult blood testing cannot be recommended as it 

lacks the required sensitivity and specificity. The value of 

serological tests for coeliac disease (endomysial antibodies 

(EMA) or tissue transglutaminase (TTG) antibodies) in patients 

with IBS-D depends on the population and is generally 

considered cost-effective if the incidence of coeliac disease is 

above 1%. 290 It may therefore be worthwhile in the United 

Kingdom, where up to 3% of cases of IBS-D in primary care 

have coeliac disease. 291 

6.1.5 When to refer 

Patients with alarm symptoms (see Box 5), those in whom 

there is genuine uncertainty about the diagnosis, and those 

whose concerns have not been successfully allayed in their 

consultations with the GP should be referred for a specialist 

opinion. Twenty per cent of patients with non-specific 

abdominal complaints present over a 12 month period were 

referred to secondary care in one Dutch study. 74 

Box 7 

Questions for assessing mood in primary care 

N During the past month have you often been bothered by 

feeling down, depressed, or hopeless? 

N During the past month have you often been bothered by 

little interest or pleasure in doing things? 

N Is this something you would like help with? 

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Table 3 Recommendations for diagnosing irritable bowel 

syndrome in primary care 




N Take a symptom history Moderate Net benefit Definitive 

N Assess previous 

consultations Low Net benefit Definitive 

N Screening questions for 

depression 

N Assess psychosocial 

factors 

N Check for alarm 

symptoms 

N Investigations 

FBC 

Good 

Moderate 

Moderate 

Moderate 

Net benefit 

Net benefit 

Net benefit 

Net benefit 

Definitive 

Definitive 

Definitive 

Definitive 

EMA/TTG Good Trade-offs Qualified 

EMA, endomysial antibodies; FBC, full blood count; TTG, tissue 

transglutaminase. 

6.2 Recommendations 

A summary of the recommendations for diagnosing IBS in 

primary care is given in table 3. 

7TREATMENTOFIBS 

Treatments should be safe and proportionate. Safety is a high 

priority as IBS is non-fatal, though it should be recognised that 

for some patients symptoms markedly reduce the quality of life. 

Furthermore, as IBS is very common, cost-effectiveness is also 

important for health care providers. 

7.1 Dietary treatment 

7.1.1 Alterations in fibre intake 

Fruit and vegetable contain substantial amounts of both soluble 

(pectins, hemicelluloses) and insoluble (cellulose, lignin) nonstarch 

polysaccharide commonly referred to under the umbrella 

term ‘‘fibre’’, while cereals and especially bran contains mainly 

insoluble fibre. Although the commonest dietary recommendation 

made to patients with IBS is to increase the intake of 

dietary fibre, with particular emphasis on cereal bran, there are 

few data to support this approach. A survey based on secondary 

care patients actually suggested that cereal fibre makes the 

symptoms worse in around 55% of cases, with only 11% 

reporting any benefit. 292 Other forms of fibre, especially the 

soluble varieties, were not so detrimental. Psyllium and 

ispaghula—though they are soluble gum-forming mucilages— 

are relatively poorly fermented, which may give them unique 

advantages. These have been demonstrated in RCTs. 293 294 It is 

also interesting to note that the majority of therapeutic trials 

examining the effect of fibre in IBS have failed to show much 

benefit, and have suffered from the flaw that they were not 

designed to detect a negative effect. A recent systematic review 

of 17 clinical trials concluded that the benefits of fibre in IBS 

were marginal and that insoluble fibre can make the condition 

worse. 294 It is important to point out that none of these studies 

was undertaken in primary care, where, it could be argued, 

response to alteration of fibre intake may be more encouraging. 

It is therefore worthwhile trying a period of cereal fibre 

exclusion, especially in those patients in whom consumption is 

excessive. However, if it is felt that fibre supplementation is 

needed and this cannot be achieved by diet alone, then the 

soluble varieties (ispaghula, sterculia, or methyl cellulose) are 

probably the best choice. 

7.1.2 Role of food allergy 

The symptoms of IBS are often made worse by eating, and this 

leads many patients to conclude that they are suffering from 

some form of dietary ‘‘allergy’’. There is little evidence to 

suggest that immediate type IgE mediated reactions are 

particularly important in IBS as a whole, although in those 

who suffer from diarrhoea and also exhibit atopy, this 

mechanism may be more important 295 and oral sodium 

cromoglycate has been recommended. 296–298 However, it should 

be noted that the trials that support this—which were 

completed a decade ago within a single country—did not use 

the standard randomised placebo controlled design. In clinical 

practice this treatment is rarely used, indicating that these 

studies need to be repeated with more rigorous study designs 

before any definite conclusions can be drawn. There seems little 

doubt, however, that some patients do show some form of food 

intolerance, but the mechanisms involved in such reactions are 

not known. Currently the most robust way of identifying food 

intolerance is by double blind food challenge, although this is 

time consuming and labour intensive. In a study involving 21 

patients with diarrhoea predominant IBS, it was shown that in 

approximately 66% of cases food intolerance could be identified 

by using an exclusion diet followed serial reintroduction of 

individual foods. 299 In some of these patients the validity of the 

intolerance was confirmed by a double blind challenge. 299 There 

has been a systematic review of seven studies attempting to 

reproduce these results, which showed response rates varying 

from 15% to 71%, and it was concluded that there is insufficient 

evidence to recommend this approach routinely. 300 

Nevertheless, there is no doubt that some patients do respond 

to dietary exclusion, and this may be worth trying in the more 

refractory patients. It is important to realise that dietary 

exclusion can become problematic if the diet becomes so 

restricted as to be nutritionally inadequate, so it is best if this 

process can be supervised by a dietician. 

Dietary exclusion would be much easier if there was a simple 

test that could be used to predict which food, or foods, are likely 

to be causing problems. A wide variety of food intolerance tests 

is available ‘‘over the counter’’ but none of these has any 

evidence base and they are therefore of dubious value. 

However, there is some preliminary evidence that the measurement 

of circulating IgG antibodies to food may be successfully 

used as a guide to which foods should be eliminated from the 

diet in order to improve symptoms. 301–303 Interestingly, the foods 

identified by using IgG antibodies or an exclusion diet differ 

somewhat, suggesting that the two approaches might be 

detecting different mechanisms of intolerance. 

7.1.3 Carbohydrate intolerance 

This has been extensively investigated in IBS, 304–313 with varying 

levels of lactose, fructose, and sorbitol intolerance being 

reported. However, the prevalence of lactose intolerance shows 

considerable geographical fluctuation, which partly reflects 

racial differences in the incidence of the mutant gene that 

causes lactase persistence, which appears to have originated in 

NW Europe. Thus the incidence of adult hypolactasia is just 

10% in people of north western European origin but approximately 

40% in those of Mediterranean origin, 60% in Asians, 

and 90% in Chinese. 279 In addition, in some studies the 

prevalence of malabsorption of carbohydrates in IBS does not 

greatly exceed that observed in controls, although their 

exclusion from the diet undoubtedly benefits some patients. 

It is also worth remembering that IBS patients often show fat 

intolerance and it has been shown that lipid can induce greater 

gas retention 256 and increase visceral hypersensitivity 314 in 

patients with IBS than in healthy controls. 

In the absence of a specific test on which dietary advice can 

be based, an empirical approach is still necessary. Adjusting the 

intake of fibre, carbohydrate, and fat is relatively easy before 

embarking on more complex strategies which involve excluding 

a wide range of foods and then systematically reintroducing 

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them one by one until intolerances can be identified. 315 When 

this has been done, 38–41% showed specific benefit, 315 316 the 

commonest intolerances being to dairy and wheat products. It 

should also be remembered that even normal individuals often 

have one or two foods that ‘‘upset’’ them, and IBS subjects are 

no exception to this rule. When undertaking a trial of dietary 

manipulation patients should be warned that the effect of this 

may take a few days to become apparent, because whole gut 

transit may range from one to five days in normal individuals 

and possibly much longer when there is constipation. Likewise, 

responses to offending foods may also be delayed by many 

hours. 

7.1.4 Recommendations 

A summary of the recommendations for the dietary treatment 

of IBS is given in table 4. 

7.2 Psychological treatment 

7.2.1 Introduction 

The role of psychological factors in the onset and progress of 

irritable bowel syndrome (IBS) is complex, and remains 

controversial, ranging from subtle modulations of enteric 

nervous system function and maladaptive behaviour to overt 

co-morbidity with anxiety, depression, or somatisation disorder. 

Unsurprisingly a range of psychological approaches to 

managing IBS has been developed and—because of significant 

challenges in terms of study design, patient selection, and the 

interpretation of results—some uncertainty still remains about 

the roles of psychological therapies in management. 

7.2.2 Psychological approach to management 

Most patients with IBS are managed in primary care, where the 

mainstay of treatment is explanation and reassurance in terms 

understandable to the patient, coupled with sensible advice 

about lifestyle, including diet and stresses and, when possible, 

symptom control. A psychological approach to management 

should be integrated into the first consultation. Eliciting the 

patient’s reason for consulting and their views on the causes of 

their symptoms is essential. Fears of cancer or other serious 

illnesses are common, and are important reasons for seeking 

medical attention. 59 Patients who attribute their symptoms to 

physical illness rather than to stress are more likely to be 

referred from primary to secondary care and consult their 

19 317 

general practitioner more often. 

In secondary care the patient who fears serious illness is 

more likely to be reassured if the doctor has correctly 

determined, at the first interview, whether the symptoms are 

attributed to stress or to physical illness. 318 Interestingly, 

Table 4 Summary of recommendations for the dietary 

treatment of irritable bowel syndrome 




1. Take a careful dietary 

history to identify potential 

causes of symptoms 

2. Assess dietary fibre intake 

and consider recommending 

an increase or decrease 

accordingly 

3. Trial of exclusion of wheat 

bran or lactose 

4. Consider systematic modification 

of diet to identify 

intolerances 

Very low 

Low 

Low 

Low 

Net benefit 

Net benefit 

Trade-offs 

Trade-offs 

Qualified 

Qualified 

Qualified 

Qualified 

marked fears of serious illness do not appear to be allayed by 

numerous investigations or consultations, whereas seeing the 

same doctor at different consultations does seem to be 

important. 318 

A 30 minute standardised gastroenterology consultation, 

which includes a positive diagnosis, patient education using a 

leaflet, and explicit reassurance about the absence of serious 

illness, may be followed by a reduced number of consultations 

for gastrointestinal symptoms and less pain. 319 Such management 

does not, however, appear to be followed by improvement 

in health related quality of life or reduced anxiety about 

numerous bodily symptoms. 319 This is important, because when 

anxiety, depression, or somatisation disorder are present, 

patients are not reassured by normal investigations, 320 they 

consult more frequently, and have an impaired quality of life. 321– 

323 

It is important that psychological co-morbidity is detected 

and effectively treated in IBS, as discussed later. 

7.2.3 Evidence for psychological therapies 

Two recent systematic reviews of psychological treatment in 

324 325 

IBS provide a useful summary of most relevant studies. 

One is guarded in its support for psychological treatments, 324 

pointing to major design issues with many trials, including the 

robustness of the control groups and the blindness of 

assessments. Eight studies 326–333 were identified as being of 

acceptable methodological quality in both reviews, and four of 

these showed a clear benefit to patients in terms of IBS 

symptoms and included studies of cognitive behavioural 

therapy (CBT), psychotherapy, and multicomponent behaviour 

307 308 312 333 

therapy. The second review, adopting careful and 

innovative methodology to select and analyse the studies, 

found that psychological treatments were significantly superior 

to controls in terms of improvement in abdominal pain, bowel 

dysfunction, depression, and anxiety. 334 The meta-analyses 

were not entirely satisfactory because two thirds of the trials 

had been undertaken at the same centre in the USA, at which a 

waiting list control was used rather than a true attention 

control. This review concluded that there was overall evidence 

of efficacy for psychological treatments, with little to choose 

between the various forms. 

Three larger trials employing more rigorous methodology 

have subsequently been published, 112 335 336 adding further 

support for the efficacy of CBT and psychotherapy, either alone 

or in conjunction with antidepressant drug treatment. 

Interpretation of these trials is made difficult by the fact that 

they have been conducted in different settings, including the 

general population, 326 primary care, 112 gastroenterology 

clinics, 335 and in patients with chronic or treatment resistant 

IBS. 336 It is likely that patients recruited after failure of short 

term treatment in primary care 112 have less severe IBS than 

those recruited from gastroenterology clinics, who have failed 

to respond to the usual treatments. 336 In spite of this there is 

some evidence that psychological treatment for different types 

of somatic complaints (including IBS) is more effective when 

delivered to patients in tertiary care than in community 

settings. 337 

7.3.4 The psychological therapies 

Anxiety and depression are common in IBS, 105 and patients 

report a close relation between stress and hassles and their gut 

symptoms, 338 providing a pragmatic rationale for psychological 

therapy. 

7.3.4.1 Relaxation training 

This is useful when stress causes exacerbation of symptoms, 

which can be relieved by progressive muscle relaxation, 

339 340 

biofeedback, and transcendental or yoga meditations, 

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although it is unclear how much of the benefit is the result of 

the non-specific factor of increased attention from a therapist. 

341–343 

7.3.4.2 Cognitive behavioural therapy 

CBT is also based on the assumption that IBS symptoms are a 

response to stressful life events or daily hassles, producing 

maladaptive behaviour and inappropriate symptom attributions. 

Treatment involves identifying the triggers for symptom 

exacerbation, understanding the patient’s response to symptoms, 

and teaching more adaptive ways of responding. The 

evidence for the efficacy of CBT remains controversial, 

112 327 335 344 with the most recent study in primary care—in 

which CBT was combined with mebeverine—showing symptom 

improvement at up to three months, and improved work 

and social adjustment up to one year. A larger study in 

secondary care found little effect on abdominal pain or IBSspecific 

quality of life, although satisfaction and global wellbeing 

were improved. 335 Both studies suggest that CBT may help 

patients cope with their symptoms without necessarily abolishing 

them. 

7.3.4.3 Psychodynamic interpersonal therapy 

Psychodynamic interpersonal therapy (PIT) attempts to provide 

the patient with insights into why symptoms developed in the 

context of difficulties or changes in key relationships. As well as 

helping the patient understand how emotional state is related 

to stress, the link between emotions and bowel symptoms may 

also become clearer. 345 When successful, this treatment may 

lead to significant life changes as well as to an improvement in 

328 333 345 

emotional state and IBS symptoms. 

Two studies of PIT compared with ‘‘supportive listening’’ 

with the same therapist, showed significant improvements 

compared with the comparison groups, and a large costeffectiveness 

trial has shown that short term PIT is widely 

acceptable and leads to a significant improvement in health 

related quality of life and a reduction in health care costs. 336 

Hypnotherapy, which is an important psychological treatment, 

is described later (7.4). 

7.3.5 Choosing patients for psychotherapy 

Patients with constant as opposed to intermittent abdominal 

pain and constipation tend to do poorly with PIT—the large 

trials of CBT and PIT in secondary care reported no improvement 

in patients with depression. PIT was particularly 

323 335 

successful in patients who reported a history of sexual 

abuse. 336 346 In the primary care CBT trial, 112 a poor response to 

therapy was found in men who believed in a physical cause for 

their symptoms. Few data are available, however, to guide the 

timing of psychological therapies, although the temptation to 

withhold them for ‘‘refractory’’ patients should, perhaps, be 

tempered by the recognition that they may provide effective 

alternatives or adjuncts to existing drug treatments, although 

there are few comparative trials. 

The choice of psychological treatment will depend on what 

type of therapy is available locally and on patient preference. 

Some patients are very reluctant to accept that psychological 

therapy is necessary, but may be prepared to take a small dose 

of an antidepressant to see if it helps the pain or other 

symptoms. Many more patients are prepared to accept that 

psychological factors could be important and would prefer a 

psychological, or ‘‘talking’’, therapy to drug treatment. As 

patients who do not wish to take antidepressants gain no 

335 336 

benefit from them. it is important to elicit and respect 

patients’ preference for type of treatment. 

7.3.6 Recommendations 

All approaches to managing IBS should be informed by 

psychological understanding, recognising that the most important 

aspect of management is the relation between the patient 

and the physician. Empathic listening, respecting patients’ 

views of symptom causation, and giving honest, clear explanations 

of the interplay between psychological and physical 

symptoms are essential. Conversely, collusion in seeking a 

physical cause and undertaking endless investigations must be 

resisted. 

Referral for a psychological treatment in primary care should 

be considered if the patient wishes this or if there are marked 

anxiety or depressive symptoms. There has recently been a 

general increase in the availability of ‘‘talking’’ therapies in 

primary care. In secondary care, more specialised psychological 

treatment, focused on IBS, is preferable if it is available. 

Gastroenterologists are encouraged to develop close links with a 

particular psychotherapist or hypnotherapist as this facilitates 

referral of patients, who may express reservations about such 

treatments unless they are made to seem part of the entire 

process and not as a rejection by the gastroenterologist. 

A summary of the recommendations for the psychological 

treatment of IBS is given in table 5. 

7.4 Hypnotherapy 

7.4.1 Evidence of benefit 

The first controlled trial assessing the value of hypnotherapy in 

IBS patients refractory to other treatments was reported in 

1984. 347 In that study hypnotherapy was shown to produce a 

significantly greater improvement over a three month period 

than supportive therapy combined with the administration of a 

placebo drug. Since that time continuing evidence for its value 

348 349 

has accrued, and there has recently been a systematic 

review of published reports assessing the efficacy of hypnotherapy 

in IBS. 350 In the 14 studies identified, of which only six 

included a control group, 599 patients were treated with 

hypnotherapy and 100 received some form of control treatment. 

It was concluded that, according to the clinical psychology 

division of the American Psychological Association guidelines, 

hypnotherapy qualified for the highest level of acceptance as 

being both effective and specific. 350 There is also some 

preliminary evidence that a home hypnosis programme might 

be useful, although the response rate is not so high as that in 

therapist led treatment, 351 and it is therefore probably not 

suitable for the more severe cases seen in referral centres. One 

particular advantage of hypnotherapy is that, rather than just 

relieving a single symptom, it has been shown that it improves 

many of the features of the condition, including quality of life 

and psychological status. 111 Furthermore, the beneficial effects 

appear to be sustained over time, with patients reporting 

continued relief from symptoms for at least five years. 352 

7.4.2 Mechanisms 

There has been some research into establishing how hypnotherapy 

might mediate its beneficial effects. There is 

evidence to suggest that in patients with IBS, it normalises 

visceral sensation, 353 reduces colonic phasic contractions, 354 and 

reverses the patients’ negative thoughts about their condition. 

355 As has already been discussed above, the activation of 

the certain areas of the brain, especially the anterior cingulate 

cortex, in response to a painful rectal stimulus appears to be 

exaggerated in IBS compared with controls. It is therefore of 

interest that hypnotic reduction of somatic pain is associated 

with a reduction in activation of this particular region, 356 

suggesting that hypnotherapy might enable IBS subjects to 

modify their central response to pain. 

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Table 5 Summary of recommendations for the psychological treatment of irritable bowel 





N Make a positive diagnosis and provide a clear explanation of 

the cause and nature of symptoms and an honest appraisal of 

prognosis and treatment options Medium Net benefit Qualified 

Psychological approaches to treatment 

N Relaxation therapy Moderate Trade-offs Qualified 

N Patients with moderate anxiety, not amounting to psychiatric 

disorder, who do not respond satisfactorily to standard 

treatment may benefit from relaxation therapy Moderate Trade-offs Qualified 

N Cognitive behavioural therapy Moderate Trade-offs Qualified 

N Psychodynamic interpersonal therapy Moderate Trade-offs Qualified 

N Specific psychological treatment for coexisting 

psychopathology High Net benefit Definitive 

7.4.3 Problems with application 

Hypnotherapy, like all behavioural treatments, suffers from 

several disadvantages, especially in terms of its lack of 

availability and lack of therapists adequately qualified to 

provide it. It is labour intensive, requiring as many as 12 onehour 

sessions of treatment, as well as being extremely operator 

dependent and therefore subject to variation in the quality of 

provision. Although most individuals can be hypnotised, for a 

successful therapeutic application there must be regular 

practice and commitment on the part of the patient, without 

which it is likely to fail. The best evidence for effectiveness is in 

patients refractory to standard treatments, so its efficacy as first 

line treatment is uncertain. Thus this form of treatment is 

probably best reserved for the more refractory patients, who 

could then be treated in a limited number of specialist centres 

where hypnotherapy can be integrated into an overall care 

package. 357 

A summary of the recommendations for hypnotherapy in the 

treatment of IBS is given in table 6. 

7.5 Pharmacological treatments for IBS 

7.5.1 Overview 

Various pharmacological agents have been tried in the management 

of IBS, but these have proved of limited efficacy for the 

cardinal symptoms of abdominal pain and bloating. 

Therapeutic targets for these symptoms have changed over 

the years, initially focusing on relaxing the smooth muscle of 

the gut, latterly evolving into attempts to alter gut transit and to 

modulate the perception of visceral afferent information in the 

CNS. Treatment of bowel dysfunction is comparatively more 

straightforward, aimed at accelerating or slowing transit as 

required. The placebo response of up to 40–50% in IBS 

358 359 

trials confounds interpretation of many drug studies. 

Table 6 Summary of recommendations for hypnotherapy 

in the treatment of irritable bowel syndrome 




N Hypnotherapy for patients 

refractory to standard 

treatment 

N Hypnotherapy works best for 

Those without major 

psychiatric disease 

Moderate 

Low 

Trade-offs 

Trade-offs 

Qualified 

Qualified 

Meta-analyses have shown that the placebo response is 

increased by more frequent dosing and by doctor/patient 

interactions. Several investigators have pointed out that rather 

than regarding this as a problem physicians should be 

360 361 

harnessing the effect. 

7.5.2 Antispasmodic agents 

The rationale for using antispasmodic agents is to attenuate the 

heightened baseline and postprandial contractility seen in 

patients with IBS (particularly when diarrhoea predominant). 

151 The efficacy of antispasmodic agents has been the 

subject of several meta-analyses. 362–366 Of the various agents 

shown to have some efficacy in these studies, only two are 

licensed in the United Kingdom—mebeverine (135–150 mg 

three times a day) and hyoscine (10–20 mg four times a day). 

Comparisons between these and more recently developed 

drugs are difficult because at the time when the earlier drugs 

were developed the trials were much smaller than they are now, 

and by comparison underpowered. There may also have been a 

publication bias. A recent meta-analysis 364 366 give an odds ratio 

for benefit of 2.1 and global improvement of 56% for active drug 

vs 38% for placebo, and a number needed to treat (NNT) of 5.5. 

Relief of pain was seen in 53% and 41%, respectively, giving an 

NNT of 8.3. The odds ratio for benefit must be interpreted with 

caution as in a much larger modern trial of mebeverine vs 

alosetron (see below), alosetron was shown to be more effective 

than antispasmodic agents, with an odds ratio of benefit of only 

1.7, 367 which is not much different from its benefit over placebo 

in other trials. Furthermore, these drugs do not seem to have 

any beneficial effect on the symptoms of diarrhoea or 

constipation. 365 Other antimuscarinic agents licensed in the 

United Kingdom lack RCT evidence of effectiveness (alverine 

citrate 368 ) or are associated with significant side effects 

(dicycloverine). 364 Mebeverine is generally well tolerated and 

can be used on an as required basis (before meals) and hence is 

sometimes employed when simple reassurance fails to improve 

symptoms. Other classes of antispasmodic—for example 

calcium channel blockers 369 and opioid antagonists such as 

trimebutine 370 —have been shown to produce inconsistent 

benefit in IBS and have been made available in only a few 

countries worldwide. 

7.5.3 Antidepressants 

It is important that patients’ preferences are taken into account 

when deciding whether to recommend antidepressants or 

psychological treatment, as both require good patient compliance 

to be effective. 

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7.5.3.1 Tricyclic antidepressants 

The tricyclic antidepressants are drugs with anticholinergic and 

non-selective serotonin reuptake inhibitor effects. Tricyclic 

antidepressants are widely used in other specialties for their 

ability to potentiate analgesics, with NNT ranging from 2.3 to 

3.6. 371 The drugs may alter pain perception, 372 especially during 

acute stress, 227 independent of their antidepressant or antianxiety 

effect (for a review, see Clouse and Lustman 373 ). 

Approximately 10% of IBS patients, usually those with 

refractory symptoms, are tried on the tricyclic antidepressants. 

105 

Several randomised placebo controlled studies have shown 

that low dose tricyclic agents effectively decrease symptoms. 

Although a meta-analysis has suggested a beneficial odds ratio 

of 4.0 compared with placebo, with an NNT of 3, 374 this metaanalysis 

was strongly influenced by a single trial that appeared 

362 375 

to be a clear outlier. If that study is excluded then no 

benefit remains, in keeping with the largest and most recent 

study in which no benefit was seen when analysed on an 

intention to treat basis (though benefit was seen in those able 

to tolerate the drug, with an NNT of 5.2). 335 Five tricyclic agents 

have been studied formally (amitriptyline, trimipramine, 

desipramine, clomipramine, and doxepin), in addition to the 

anti-serotonin agent mianserin. The effect of these agents 

primarily relates to pain, and it has been suggested that 

patients with diarrhoea predominant IBS obtain the greatest 

benefit. 335 

Even with low doses, side effects of constipation, dry mouth, 

drowsiness, and fatigue occur in over one third of patients 

treated with tricyclic agents. The number needed to harm with 

these drugs is 22. 371 These side effects often preclude good 

compliance, and so it is essential that the prescriber counsels 

the patient adequately about the potential for developing these 

problems, in addition to explaining the nature of the drug and 

the need to try it for at least four weeks (though effects may be 

seen as soon as one week 335 376 ). The hypnotic side effect can be 

minimised or taken advantage of by night time dosing, and 

daily administration—starting at a dose of 10 mg for any of the 

tricyclic antidepressants, with a gradual increase to 25 to 100 

mg—has been suggested. 377 The drug should be continued for 6 

to 12 months, after which dose tapering may be attempted. 377 It 

should be noted that IBS patients, who show hypersensitivity to 

many stimuli, are often hypersensitive to drug side effects. 

Many practitioners therefore find the lower dose range (initially 

10 mg increasing as tolerated up to 30 mg at night) is the most 

useful. 

7.5.3.2 Selective serotonin reuptake inhibitors 

Selective serotonin reuptake inhibitors (SSRIs) are widely 

prescribed and well tolerated in the treatment of anxiety, 

depression, and somatisation disorders. 378 There have been four 

randomised controlled trials of SSRIs in IBS, but only one of 

reasonable size. This large cost-effectiveness trial showed that a 

standard dose of an SSRI antidepressant leads to a significant 

improvement in health related quality of life at no extra cost in 

patients with chronic or treatment resistant IBS. 309 All four 

studies showed global benefit without significant change in 

336 379–381 

bowel symptoms or pain. After the trial, patients on 

SSRIs were more likely to want to continue with the drug (84% 

vs 37% on placebo) so plainly they are providing benefit even if 

they do not change bowel symptoms. SSRIs have been shown 

to benefit patients with somatisation, 382 a common feature of 

more severe IBS. Treatment of this aspect may underlie the 

global improvement and why patients wish to continue with 

treatment. 

7.5.4 Fibre and laxatives 

Constipation is a common complaint in patients with IBS. Fibre 

supplementation with naturally derived concentrated nonstarch 

polysaccharides such as bran, ispaghula husk, methylcellulose, 

and sterculia increases faecal mass and may accelerate 

transit. The odds ratio for benefit in global symptom relief 

with fibre is 1.33, but although constipation symptoms may 

improve there is no benefit for abdominal pain. 294 As already 

mentioned above, overall only 10% of patients are improved by 

such bulking agents, and insoluble fibre (such as bran) has 

been shown in randomised placebo controlled trials to have no 

effect on pain and to exacerbate flatulence and bloating. 383 This 

is recognised by IBS patients, of whom around half report that 

bran aggravates their symptoms. 292 Inorganic salts (for example, 

magnesium salts and polyethylene glycol based laxatives) 

act as an osmotic laxative and are effective and well tolerated in 

chronic constipation, 384 though data are lacking in IBS-C. These 

inorganic salts are preferred to organic alcohols and sugars, 

which are more expensive and may promote flatulence. One of 

the few randomised controlled trials in chronic constipation 

showed that polyethylene glycol was superior in efficacy and 

tolerability to lactulose, with less flatulence. 384 Stimulant 

laxatives act erratically and are associated with tachyphylaxis 

and dependency. Stimulants are therefore generally recommended 

only for occasional use. 

7.5.5 Antidiarrhoeal agents 

The opioid analogues loperamide and diphenoxylate stimulate 

inhibitory presynaptic receptors in the enteric nervous system 

resulting in inhibition of peristalsis and secretion. Loperamide 

reduces diarrhoea in patients with IBS 385 but has little effect on 

abdominal pain. 386 No such studies have been undertaken with 

cophenotrope (diphenoxylate–atropine) but loperamide is 

preferred as it causes neither confusion nor anticholinergic 

side effects. Codeine phosphate is also not favoured because of 

its potential for dependence and its tendency to induce nausea 

and dysphoria. 387 Loperamide and cophenotrope can be used 

both as regular medication and also on an as required basis. 

Tachyphylaxis does not develop with chronic dosing. 

Loperamide has particular potential value in that it is available 

in syrup formulation for fine tuning of dose to minimise the 

adverse effect of constipation. 

Bile acid malabsorption has been variably reported in 

diarrhoea predominant IBS. 388 However, this has to be severe, 

with less than 5% of bile acid retained at seven days, before a 

reliable response to treatment can be expected. 281 Such patients 

made up approximately 10% of Williams’ series of unexplained 

bile acid malabsorbers. Responders are often those with an 

acute, presumed infective onset 389 280 390 

and nocturnal diarrhoea. 

7.5.6 Serotonin receptor agonists/antagonists 

Serotonin (5-HT), acting particularly through the 5-HT 3 and 5- 

HT 4 receptors, plays a significant role in the control of 

gastrointestinal motility, sensation, and secretion. 391–393 

Furthermore, recent observations that plasma 5-HT concentrations 

are reduced in IBS patients with constipation, but 

169 240 

169 394 

raised in those with diarrhoea, especially those showing 

postprandial symptoms, 394 provide further support for its 

involvement in the motor and sensory dysfunction associated 

with this condition. Thus there has been considerable interest 

in these receptors as possible therapeutic targets for IBS, with 

agonists at the 5-HT 4 receptor predicted to enhance gastrointestinal 

propulsion (that is, to be prokinetics) and 

379 395 396 

antagonists at the 5-HT 3 receptor to slow gastrointestinal 

379 397–399 

transit and reduce visceral sensation. 

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7.5.6.1 5-HT 4 receptor agonists 

8Tegaserod is a selective partial agonist at the 5-HT 4 receptor, 

available in the USA since 2002 and in many other countries, 

though not in Europe, for the treatment of IBS with 

constipation. Tegaserod has been assessed in multiple, large, 

379 395 400 401 

and well designed clinical trials and has also been 

shown to have promotility effects in both the small and the 

large bowel. 396 A Cochrane review identified seven high quality 

placebo controlled trials of tegaserod in IBS-C, which included 

4040 patients treated for up to a maximum of 20 weeks, and a 

small study in IBS-D. 401 Again, a small benefit was identified, 

with a relative risk (RR) of global relief of gut symptoms with 

tegaserod at 6 mg twice daily of 1.19 (95% confidence interval 

(CI), 1.09 to 1.29; NNT = 14) and at 2 mg twice daily of 1.15 

(1.02 to 1.31; NNT = 20). The most improved symptoms were 

those related to defecatory frequency. A more recent randomised 

controlled trial conducted in 2660 female patients, with 

1191 entering a repeat treatment phase, showed that global 

and individual symptoms were significantly improved by 

tegaserod in both phases (33.7 vs 24.2% and 44.9 vs 28.7%, 

respectively). 69 Extended use studies suggest that benefit 

continues to be experienced (Am J Gastroenterol 2006;101: 

2558–69). 

In addition, quality of life was also significantly improved. 69 

Other recent studies have similarly shown a positive effect on 

quality of life, 402 403 and a decrease, although small, in 

absenteeism from work (2.6%) and activity impairment 

(5.8%). 404 It should be noted that, as there have been no direct 

comparisons, it is unknown whether this agent superior to 

older stimulant laxatives. The commonest side effect of 

tegaserod 6 mg twice daily is predictably diarrhoea (RR = 2.75 

(95% CI, 1.90 to 3.97)), with the number needed to 

harm = 20. 401 Despite initial good experience concerning safety, 

the use of tegaserod has recently been restricted owing to 

concerns about an apparent small excess of cases of myocardial 

ischaemia and stroke (13 events per 11 614 patients treated) 

(see www.fda.gov/cder/drug/advisory/tegaserod.htm). Whether 

this will prove to be a problem with other 5-HT 4 agonists under 

development remains uncertain. 

7.5.6.2 5-HT 3 receptor antagonists 

Alosetron, a selective 5-HT 3 receptor antagonist used for the 

treatment of female IBS patients with diarrhoea, has recently 

been reapproved by the US Food and Drug Administration after 

being withdrawn in the USA in 2000 because of side effects of 

constipation and ischaemic colitis. 405 It is unavailable for use in 

any country other than the USA. Meta-analyses have shown it 

to be helpful in women with IBS-D (odds ratio = 2.2 (95% CI, 

1.9 to 2.6)), 400 406 being more effective than placebo at inducing 

adequate relief of abdominal pain and discomfort, and 

improvement in bowel frequency, consistency, and urgency of 

bowel movement, 379 400 with NNT = 7. 406 Again extended use 

studies suggest that the benefit continues as long as the drug is 

taken. 407 

7.5.6.3 Developmental 5-HT drugs 

Cilansetron, another 5-HT 3 receptor antagonist for the treatment 

of IBS-D, has been reported in two RCTs published in 

abstract form to relieve abdominal pain or discomfort and 

abnormal bowel habit in both male and female patients at three 

and six months. 408 409 Renzapride—a mixed 5-HT 4 receptor 

agonist/5-HT 3 receptor antagonist—has been shown to accelerate 

colonic transit in a small, randomised placebo controlled 

trial for two weeks in patients with IBS-C but to be without 

effect on symptoms. 410 

7.5.7 Alternative pharmacological strategies 

7.5.7.1 Antibiotics and probiotics 

Approximately three quarters of IBS patients have been found 

to have a positive lactulose hydrogen breath test, defined as a 

double peak in breath hydrogen, the first occurring less than 90 

minutes after ingestion, with a rise of more than 20 parts per 

million. 411 The significance of this is disputed, as double peaks 

can be seen once lactulose reaches the colon and do not usually 

represent fermentation within the small bowel. 412 However, the 

investigators interpreted this finding as suggestive of the 

presence of small intestinal bacterial overgrowth, 411 providing 

the rationale for antibiotic treatment. When given a 10 day 

course of broad spectrum antibiotics (neomycin, ciprofloxacin, 

metronidazole, or doxycycline), one third of these patients 

became asymptomatic, at least in the short term. 413 A similar 

result has been seen in an RCT of rifamixin which showed 

benefit lasting up to 10 weeks after treatment. 414 . 

No other group has adopted this treatment, which cannot be 

recommended until replicated in well designed studies by 

others. An elemental diet has been shown to normalise the 

lactulose hydrogen breath test, possibly because of alteration in 

gut microflora. 415 Again, the durability of this response is 

unknown. 

Probiotics are a more attractive though possibly less effective 

way of altering bowel flora, and five randomised placebo 

controlled trials of probiotics have shown benefit for some 

symptoms, notably bloating and flatulence, using a variety of 

probiotic agents including Lactobacillus rhamnosus plantarum and 

VSL#3, a mixture of lactobacilli, bifidobacteria, and a 

streptococcus. 416–420 A more recent study using Bifidobacterium 

infantis suggested benefit and linked this to a downregulation of 

immune response, 246 but this finding also needs to be replicated. 

A subsequent larger study 421 has confirmed the benefit of 

B infantis, though problems with formulation mean that further 

studies are needed before this can be firmly recommended. 

7.5.7.2 Miscellaneous agents 

An alternative approach to modifying neuroimmunology of the 

gut is to use an immunosuppressive agent. There has been only 

one small placebo controlled trial of prednisolone 30 mg which 

failed to show a beneficial effect after three weeks. 422 Similar 

disappointing results with leuprolide—a gonadotrophin releasing 

hormone antagonist that induces a medical menopause— 

mean that this approach cannot be recommended either. 423 

Three underpowered placebo controlled studies looked at the 

D2 antagonist domperidone: two found no effect 424 425 but the 

third reported significant improvement in flatulence, pain, and 

altered bowel habit compared with placebo. 426 

Herbal preparations have also been the subject of several 

trials. The plant preparations (STW-5 containing bitter candytuft, 

chamomile flower, peppermint leaves, caraway fruit, 

liquorice root, lemon balm leaves, celandine herbs, angelica 

root, and milk thistle fruit) have been shown to improve overall 

IBS scores and abdominal pain but it is unclear which is the 

active ingredient. 427 A longer study of 16 weeks with Chinese 

herbal preparations reported significant symptom alleviation. 428 

Herbal mixtures individualised for each patient by Chinese 

medical practitioners were compared with a standardised 

mixture of 20 herbs and found to offer no advantage. As with 

probiotics, this area of treatment is attractive to patients and 

needs further studies with well characterised preparations to 

help elucidate which formulations will benefit which patient 

groups. 

A summary giving details of all the studies cited here is 

provided in appendix 2, which is available online at the journal 

website (http://www.gutjnl.com/supplemental). 

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7.5.8 Sequence of treatments 

Given that most treatments benefit only a minority, it will often 

be logical to try a sequence of treatments, starting with the 

safest and least expensive drugs. However, the reader should be 

aware that the sequences shown in table 7 are based on expert 

opinion only and the effectiveness of such strategies needs to be 

tested in controlled trials. The evidence for bloating is 

particularly weak; however, recent studies suggest that it is 

important to distinguish between the perception of bloating 

and visible distension. Both symptoms together are associated 

with constipation and may respond to laxatives. 251 Another 

approach in non-constipated subjects might be to try reducing 

dietary fibre, particularly excluding wheat bran. By contrast, 

bloating without distension may be caused by visceral 

hypersensitivity 429 for which tricyclic agents may be a more 

logical treatment. Some probiotics have been shown to benefit 

bloating, but more experience is needed before definitive 

recommendations can be made. A summary of the recommendations 

for the pharmacological treatment of IBS is provided in 

table 8. 

8 TREATMENT IN PRIMARY AND SECONDARY CARE 

8.1 Spectrum of severity in primary care 

Patients with IBS managed in primary care comprise the entire 

spectrum, from those with mild or ill defined symptoms to 

those with severe or persistent problems. In contrast, those 

referred to a specialist are more likely to be at the more severe 

end of the spectrum—in terms of both physical symptoms and 

psychopathology—and primary care management has proved 

to be difficult or ineffective. In the United Kingdom up to 29% 

of patients with IBS are referred to a specialist 19 but the 

majority of these will return to their general practitioners for 

long term management. 

Treatment approaches in primary care are influenced by the 

awareness that functional diseases present with a variable 

combination of undifferentiated symptoms, many of which— 

such as tiredness or backache—are non-gastrointestinal and 

non-specific. The specialist led diagnostic criteria for IBS, such 

as the Manning or Rome criteria, are not commonly known or 

applied in primary care, where the management approach is 

more likely to reflect the presenting problem. A formal 

diagnosis of IBS is not necessarily made, even though 

treatments which are recognised as being associated with IBS 

might be used. 430 For example, constipation is often diagnosed 

as a problem in its own right and managed as such rather than 

identified as a possible symptom of IBS. In contrast, patients 

with loose motions are more likely to be asked about other 

symptoms such as bloating and to receive a formal label of IBS. 

A rigid distinction between the different subtypes of IBS 

(constipation or diarrhoea predominant or alternating) is often 

difficult to achieve in practice, and in a large community survey 

Table 7 Suggested sequence of pharmacological 

treatment for irritable bowel syndrome 

Predominant symptom First line 

Second line 

Pain Antispasmodic Tricyclic antidepressives 

agents 

Hypnosis 

Psychological treatments 

Diarrhoea Loperamide 5-HT 3 antagonist* 

Constipation Ispaghula 5-HT 4 agonist* 

Bloating with distension Dietary manipulation Probiotics 

Polyethylene glycols 5-HT 4 agonist* 

Bloating without Antispasmodic agents Probiotics 

distension 

Tricyclics 

*No representative of this class of drugs is currently licensed for IBS in 

Europe but there are other related drugs in development. 

there was a substantial mismatch between categorisation based 

on the Rome II criteria and the patients’ own classification. 38 

8.2 Nature of the relation between the patient and the 

primary care doctor 

Various other factors are specific to primary care, influencing 

the management and distinguishing it from secondary care. 

First, patients tend to have a long term, longitudinal consultation 

pattern with their general practitioners, and time plays an 

important role in the understanding of the problem by the 

patient and the evolution of its management. This enables 

treatment to take place through a series of steps which may be 

characterised by the use of different treatments or types of 

management, including drugs and psychological interventions. 

Second, the recurrent, relapsing, and non-lethal nature of 

IBS—including a change in the pattern of symptoms to involve 

other systems 29 —enables both the patient and the clinician to 

come to terms with the problem using remedies that appear 

effective. Finally, it is known that only a minority of IBS 

sufferers consult a doctor. While those doing so probably have 

more severe symptoms and are seeking an explanation, they do 

not necessarily want a prescription medication. 

8.3 Use of self management 

Most patients will have tried various approaches to self 

29 430 

management of their IBS. In two large community studies, 

37% of IBS sufferers had not consulted a health professional at 

all, 60% had tried an over-the-counter remedy, 47% had altered 

their diet, and a large number of complementary health carers 

had been consulted. Substances used included laxatives, 

supplements, and various ‘‘natural remedies’’. A range of self 

help organisations offers advice and information which may 

assist patients to manage and come to terms with their 

condition (for example, the IBS Network, available at 

www.ibsnetwork.org.uk). 

8.4 Prescribed drugs in primary care 

Prescribed drugs in primary care do not differ substantially 

from those in secondary care. Commonly used medicines, 

irrespective of their actual effectiveness, are the bulking agents 

(ispaghula), laxatives (osmotic or stimulant), antispasmodics, 

and antidepressants. 74 With regard to antidepressants, general 

practitioners have considerable experience in their use because 

psychological problems are commonly managed in primary 

care. As general practitioners tend to take a holistic approach 

they are comfortable with exploring psychological factors 

associated with IBS; indeed, a consideration of psychological 

factors is often prominent in making the diagnosis and in 

influencing treatment. 

8.5 Psychological approaches in primary care 

Recent research suggests that many IBS patients are not 

committed to seeking a somatic explanation for their symptoms 

and they readily accept the possibility of a psychological 

contribution to their gut problems. 431 Allied with the use of 

the drug treatment, GPs commonly use counselling and other 

psychological therapies. Many general practices have in-house 

counsellors; while these are not trained to deal specifically with 

IBS, most have strategies for the management of anxiety and 

somatisation. Research has supported the use of cognitive 

behaviour therapy. 112 Though this not routinely available in 

primary care, it can be accessed in some localities without 

referral to a gastroenterologist. Hypnotherapy for IBS has been 

shown to be effective in specialist centres (see 7.4) and new 

data from general practice suggests that this is effective during 

the first three months, although the effect is less marked after 

that. 432 A recent report has also highlighted the success of a 

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Table 8 Summary of recommendations for pharmacological treatment of irritable bowel 





Comments 

Antispasmodics 

Mebeverine Low Net benefit Qualified 

Alverine citrate Very low Uncertain trade-offs Definitive 

Dicyclomine Very low Uncertain trade-offs Definitive 

Fibre supplements 

Ispaghula High Net benefit Definitive 

Bran High No net benefit Definitive Half are made worse 

Opioids 

Loperamide High Net benefit Definitive Helps diarrhoea but less effect 

on pain/discomfort 

Tricyclic antidepressants 

Desimipramine Moderate Trade-offs Qualified Ineffective on intention to treat 

analysis 

Poorly tolerated at full dose 

Amitriptyline Low Trade-offs Qualified Poorly tolerated at full dose 

Nortriptyline 

SSRIs 

Better tolerated than TCAs 

Paroxetine High Net benefit Qualified Global benefit without benefit to 

specific bowel symptoms 

Fluoxetine High Net benefit Qualified Global benefit 

5-HT 4 agonists 

Prokinetic; benefit IBS-C 

Tegaserod High Net benefit Definitive NNT = 14 

5-HT 3 antagonists 

Antidiarrhoeal; benefit IBS-D 

Alosetron High Trade-offs Definitive NNT = 7 

‘‘Ischaemic’’ colitis, 1/700 

Probiotics Moderate Trade-offs Qualified 

Antibiotics Low Trade-offs Qualified Controversial; needs replicating 

IBS-C, constipation predominant irritable bowel syndrome; IBS-D, diarrhoea predominant irritable bowel syndrome; 

NNT, number needed to treat; TCA, tricyclic antidepressant. 

patient derived information and explanation booklet in primary 

433 434 

care, although this has not been used widely. 

8.6 Patients’ perspective 

These guidelines were reviewed by some members of the IBS 

Network, who created 10 ‘‘top requests’’ in answer to the 

question ‘‘When I visit my health professional about my IBS, I 

would like them to give me….? 

N A clear knowledgeable explanation of what IBS is. 

N A statement that there is no miracle cure. 

N A clear indication that it is my body, my illness, and that it is 

up to me to take control. 

N A clear explanation that there will be good days and bad 

days, but that there will be light at the end of the tunnel. 

N An explanation of the different treatment options. 

N Recognition that IBS is an illness. 

N Consider and discuss complementary/alternative therapies. 

N Offer at least one complementary/alternative therapy. 

N Offer support and understanding. 

N Be aware of conflicting emotions in someone who is newly 

diagnosed. 

9 APPLICABILITY OF GUIDELINES 

These guidelines are relevant to adult patients with IBS in both 

primary and secondary care. 

9.1 Organisational barriers in implementing the 

recommendations 

9.1.1 Consultation time 

IBS is a complicated condition which requires identification of 

important psychosocial factors for optimal management. Such 

patients often need longer consultations than normal in order to 

determine the role of psychological and social factors in 

exacerbating the symptoms and to offer the full explanation 

and reassurance that may be required. This is likely to prove a 

problem within fixed timed appointments. Dedicated longer time 

slots may be an appropriate way to manage the disorder rather 

than repeated brief consultations—often with different doctors— 

which usually lead to numerous negative investigations, more 

frequent attendances, and a poorer long term outcome. 

Educational booklets should be freely available, but patients 

may need the opportunity to discuss their concerns again once 

they have read such material. A suitably trained specialist nurse 

may be best suited to this task, but may not be available in 

many centres. 

9.1.2 Provision of hypnotherapy, cognitive 

behavioural therapy, or other psychological treatments 

This is limited by lack of trained practitioners and the 

reluctance of some providers to budget for it. 

9.1.3 Availability of certain drugs 

Some drugs which are of proven benefit have not been licensed 

in the United Kingdom and at present patients are left to try to 

obtain drugs themselves over the internet at their own expense. 

www.gutjnl.com



9.1.4 Training in functional gastrointestinal diseases 

Lack of adequate training leaves some gastroenterologists 

feeling uncomfortable managing such patients. Most primary 

care physicians are not aware of diagnostic criteria for IBS and 

about one third of secondary care doctors do not use them in 

practice. 261 Recent advances in knowledge and treatments mean 

that much needs to be done during training to ensure that best 

practice becomes the norm. Trainee or practising gastroenterologists 

and associated staff (for example, specialist nurses or 

other therapists) may require further training in the techniques 

of consultation suitable for IBS patients. The training of general 

practitioners usually includes generic consultation skills, but 

training in more specialised techniques of reassurance, explanation, 

and exploration of psychological factors in patients who 

prefer to speak of bodily symptoms may be helpful. 

9.2 Costs of applying the recommendations 

Costs of any condition and the cost–benefit ratio depend 

critically on whether indirect costs are included. Currently 

available drugs are cheap, though consultation time is not. 

Indirect costs can, however, be much greater. 435 These derive 

from time lost from work, which is increased by 21%, 3 and costs 

of investigations and procedures which were increased by 69% 

in one study. 3 436 These costs were based on the average IBS 

patient, but costs for the more severely affected cases can be 

much greater. 322 Annual total costs (health care and loss of 

productivity) are approximately £1000 in patients with severe 

IBS which has not responded to usual treatment, but this is 

nearly doubled in those patients who also have a depressive or 

panic disorder. 323 Both psychotherapy and an SSRI have been 

shown to improve health related quality of life in these patients 

at no extra cost. 336 Psychotherapy, but not antidepressant use, 

has been shown to reduce the direct health care costs 

significantly in patients with severe and persistent IBS, and 

psychotherapy appears also to reduce the chances of patients 

being on disability benefits. 336 However, local health authorities 

are unlikely to see the wider picture and will focus on costs 

generated within their own budget, namely the costs of 

investigations and prescribing. There is evidence that IBS 

18 437 

patients undergo more unnecessary surgery and consult 

more frequently than the normal population. 438 Whether 

optimum management will be able to show reduction in 

consultation rates and procedures is a question that requires 

urgent study. 

Increased consultation time costs money but may be costeffective 

if it saves further investigations and unnecessary 

operations. However, demonstrating that this is the case 

requires further cost-effectiveness studies. Better training in 

managing functional gastrointestinal diseases may involve 

some reorganisation of training programmes but should not 

be expected to incur much extra cost. 

9.3 Criteria for audit 

Suggested criteria for audit are as follows: improvement in 

patient satisfaction with management in primary care after 

initial diagnosis (demonstrating this would require systematic 

patient surveys using validated questionnaires); improvement 

in patient understanding of their disorder; increase in 

confidence of gastroenterologists in dealing with IBS; increase 

in the proportion of referrals to secondary care which meet 

these guidelines; reduction in the number of negative investigations 

initiated in primary care after initial diagnosis of IBS 

has been confirmed in secondary care; reduction in number of 

elective cholecystectomies in IBS patients in whom no gall 

stones are found; and reduction in number of acute appendectomies 

with normal appendices in patients subsequently 

diagnosed as IBS. 

10 SUGGESTIONS FOR FURTHER RESEARCH 

As brief perusal of our recommendations will show much of the 

available evidence is poor. Major limitations include small 

patient numbers and lack of adequate characterisation in terms 

of the variables known to affect outcomes, particularly 

psychological factors. There is therefore an urgent need for 

better research in many areas. The following list provides some 

examples: 

N Large community based follow up studies to enable a better 

definition of the natural history, in particular its relation to 

life events. 

N Improved ability to recognise food intolerances and response 

to food challenge using objective measures including genetic, 

blood, urine, and stool tests. 

N Large high quality randomised controlled trials of dietary 

manipulation in hospital-naive patients. 

N Studies of mechanisms underlying gut sensory, motor, and 

reflex changes in response to stress to identify potential 

novel pharmacological targets. 

N Improvement in behavioural assessment of visceral sensation, 

to move from current subjective measures to a 

combination of behavioural assessments, with objective 

measures such as cortical evoked potentials and autonomic 

function tests. 

N PET studies using ligands for various receptors known to be 

relevant in visceral pain may be helpful in understanding the 

neuropharmacology of visceral pain. 

N Large high quality randomised, double blind, placebo 

controlled trials to evaluate psychological therapies. 

N Large community based clinical trials comparing tricyclic 

antidepressants with SSRIs. 

N Mechanistic studies to define putative mechanisms and 

hence possible targets for treatment. 

N Community studies of behavioural interventions, including 

patient education and empowerment, should be further 

evaluated for cost-benefit. 

N Long term intervention studies are needed to determine 

whether changes in management can reduce excess surgery 

rates associated with IBS. 

A summary form of this document and appendixes 1 

and 2 are available on the journal website (http// 

www.gutjnl.com/supplemental). 

....................... 

Authors’ affiliations 

R Spiller, Wolfson Digestive Diseases Centre, University of Nottingham, 

Nottingham, UK 

Q Aziz, Department of Gastroenterology, St Barts and Royal London 

Hospital, London, UK 

F Creed, University Department of Psychiatry, Manchester Royal Infirmary, 

Manchester, UK 

A Emmanuel, Digestive Disorders Institute, University College Hospital, 

London, UK 

L Houghton, Neurogastroenterology Unit, Wythenshawe Hospital, 

Manchester, UK 

P Hungin, Centre for Integrated Research, University of Durham, Durham, 

UK 

R Jones, Department of General Practice and Primary Care, Kings College 

London, London, UK 

D Kumar, Department of Surgery, St George’s Hospital, Tooting, London, 

UK 

G Rubin, University of Sunderland, Sunderland, UK 

N Trudgill, Sandwell General Hospital, West Bromwich, UK 

P Whorwell, University Hospital of South Manchester, Manchester, UK 

www.gutjnl.com



Conflicts of interest: Professor Aziz has received remuneration for 

consultancy advice to Novartis and Mundi Pharma, and has received 

research funding from GlaxoSmithKline (GSK) and Pfizer Pharmaceuticals. 

Professor Creed has received remuneration for consultancy advice to Eli 

Lilley and Company. Dr Emmanuel has been reimbursed for travelling and 

conferences by GSK and Novartis and has received research funding from 

GSK. Dr Houghton has received remuneration for advice and speaking 

(Novartis, Solvay, Clasado), together with financial support for the conduct 

of physiological research from Novartis, GSK, and Pfizer. Professor Hungin 

has received remuneration for speaking and consulting from GSK, 

Novartis, and AstraZeneca, and research funding from Novartis. 

Professor Jones has received remuneration for speaking and consulting 

from Novartis, Solvay, Astra-Zeneca, and GSK. Professor Rubin has 

received remuneration for consultancy advice to Novartis and Tillots 

Pharma, and has received research funding from Novartis. He has shares 

in GSK. Professor Spiller has received remuneration for consultancy advice 

and received research support from Novartis Pharmaceuticals and GSK. 

He has also acted on an advisory board for Solvay Pharmaceuticals. Dr 

Trudgill has received remuneration for consultancy advice to Astra-Zeneca 

and Ferring. Professor Whorwell has received remuneration for advice and 

his department has received financial support from Novartis, GSK, Pfizer, 

Solvay, Rotta Research, Proctor and Gamble, Astellas, and Tillots. 

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