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. 2010 Jan 5;2010:0410.

Irritable bowel syndrome

Alexander Charles Ford 1,#, Per Olav Vandvik 2,#
PMCID: PMC2907616  PMID: 21718578

Abstract

Introduction

The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 receptor antagonists (alosetron and ramosetron); 5HT4 receptor agonists (tegaserod); antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]); antispasmodics (including peppermint oil); cognitive behavioural therapy (CBT); hypnotherapy; soluble and insoluble fibre supplementation; and loperamide.

Key Points

The key features of irritable bowel syndrome (IBS) are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms.

  • The prevalence of IBS varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%.

  • IBS is associated with abnormal GI motor function, enhanced visceral perception, abnormalities in central pain processing, and altered gut flora, as well as psychosocial and genetic factors.

  • People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.

  • A positive symptom-based diagnosis and a graded general treatment approach are cornerstones in the management of people with IBS.

Antidepressants (tricyclic antidepressants and SSRIs) may reduce global symptoms of IBS and abdominal pain compared with placebo.

Antispasmodics (including peppermint oil) may reduce global symptoms of IBS and abdominal pain compared with placebo.

Soluble fibre supplementation may reduce global symptoms of IBS and abdominal pain compared with placebo.

Insoluble fibre supplementation does not reduce global symptoms of IBS or abdominal pain compared with placebo, but we found no evidence from RCTs that it exacerbates symptoms.

The 5HT4 receptor agonist tegaserod reduces global symptoms of IBS and abdominal pain compared with placebo in people with constipation-predominant IBS.

  • CAUTION: Tegaserod may be associated with cerebrovascular and cardiovascular ischaemic events.

5HT3 receptor agonists (alosetron and ramosetron) reduce global symptoms of IBS and abdominal pain compared with placebo.

  • Alosetron reduces global symptoms of IBS and abdominal pain in diarrhoea-predominant IBS compared with placebo in women, but we don’t know whether it is effective in men, or whether this effect applies to those with IBS with an alternating bowel habit.

  • Alosetron may be more effective than mebeverine at reducing symptoms in women with diarrhoea-predominant IBS, but we don't know whether it is effective in men.

  • CAUTION: Alosetron may be associated with severe constipation and ischaemic colitis.

  • Ramosetron may reduce global symptoms of IBS and abdominal pain, and improve abnormal bowel habits, compared with placebo in people with diarrhoea-predominant IBS.

CBT may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term. We don't know whether it is beneficial in the longer term.

Hypnotherapy may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term.

Loperamide may reduce stool frequency in diarrhoea-predominant IBS, but it may not improve other symptoms compared with placebo.

About this condition

Definition

Irritable bowel syndrome (IBS) is a chronic functional condition of the lower GI tract characterised by abdominal pain or discomfort and disordered bowel habit (diarrhoea, constipation, or fluctuation between the two). There is no known structural or biochemical explanation for the symptoms. Symptom-based criteria, such as the Manning criteria (see table 1 ) and the latest revision of the Rome criteria, the Rome III criteria (see table 2 ), aid diagnosis, but their main use is in recruiting patients for clinical trials. The Rome III criteria subcategorise IBS according to predominant symptom (diarrhoea, constipation, or alternating bowel habit). In practice, the division between constipation-predominant and diarrhoea-predominant IBS may not be clear-cut in all people, particularly as individuals often change subcategory during follow-up. Restriction of trial entry to a subcategory of IBS limits the generalisability of some RCT results.

Table 1.

Manning criteria

Recurrent abdominal pain and two or more of the following:
- Relief of pain with defecation
- More frequent stools at the onset of pain
- Looser stools at the onset of pain
- Visible abdominal distension
- Passage of mucous per rectum
- A sensation of incomplete evacuation
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Table 1.

Rome III criteria

Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months, with symptom onset at least 6 months prior to diagnosis, associated with 2 or more of the following:
- Improvement with defecation
- Onset associated with a change in frequency of stool
- Onset associated with a change in form (appearance) of stool
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Incidence/ Prevalence

Estimates of incidence and prevalence of IBS vary depending on the diagnostic criteria used to define the condition. One cross-sectional survey conducted in the UK defined IBS as recurrent abdominal pain on more than six occasions during the previous year plus two or more of the Manning criteria (see table 1 ). It estimated prevalence in the UK to be 17% overall, with a prevalence of 23% among women and 11% among men. An Australian study reported the prevalence to be 14% using the Manning criteria, 7% using the Rome I criteria, and 4% using the Rome II criteria. A cross-sectional survey of almost 4000 individuals in the UK with 10 years of follow-up estimated the incidence of IBS, defined using the Manning criteria, to be 1.5% per year.

Aetiology/ Risk factors

The pathophysiology of IBS is uncertain, and it is unlikely that a single unifying mechanism explains the condition, but abnormal GI motor function, enhanced visceral perception, and abnormalities of central pain processing appear important. Other determinants include psychosocial factors such as a history of childhood abuse, genetic predisposition, a history of exposure to acute enteric infection, so-called post-infectious IBS, and abnormalities in gut flora.

Prognosis

A retrospective study reviewed the medical records of people with IBS (112 people aged 20–64 years when diagnosed with IBS at the Mayo Clinic, USA, between 1961 and 1963). IBS was defined as the presence of abdominal pain associated with either disturbed defecation or abdominal distension, and the absence of organic bowel disease. Over a 32-year period, less than 10% of people developed organic GI disease subsequently, and death rates were similar among people with IBS compared with age- and gender-matched controls. In another study conducted in the USA, individuals meeting diagnostic criteria for IBS were followed up for between 10 and 13 years, during which time almost 50% had undergone subsequent investigation of the lower GI tract, yet this had not led to a revision of the diagnosis of IBS in any of the subjects. Other investigators have reported that people with IBS are two to three times more likely to undergo unnecessary surgical procedures, such as cholecystectomy, hysterectomy, or appendicectomy.

Aims of intervention

To improve symptoms and reduce disability, with minimal adverse effects.

Outcomes

Symptom improvement: in particular, improvement in abdominal pain, constipation, diarrhoea, bloating, and urgency of defecation, measured using validated self-report instruments, including: adequate relief; the Irritable Bowel Severity Scoring System; the Gastrointestinal Symptom Rating Scale; the Functional Bowel Disorder Severity Index; and the IBS Symptom Questionnaire; Quality of life: measured using validated instruments, including Quality of Life and Global Impact of IBS; the Irritable Bowel Syndrome Quality of Life Measurement; the Irritable Bowel Syndrome Quality of Life Questionnaire; the Digestive Health Status Instrument; the Functional Digestive Disorder Quality of Life Questionnaire; and the Irritable Bowel Syndrome Health-Related Quality-of-Life questionnaire; Adverse effects of treatment.

Methods

Clinical Evidence search and appraisal July 2009. The following databases were used to identify studies for this systematic review: Medline 1966 to July 2009, Embase 1980 to July 2009, and The Cochrane Database of Systematic Reviews 2009, Issue 3 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing any number of individuals. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Irritable bowel syndrome.

Important outcomes Quality of life, Symptom improvement
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of treatments in people with irritable bowel syndrome?
4 (861) Symptom improvement Antidepressants versus placebo 4 –2 –1 0 0 Very low Quality points deducted for short follow-up and methodological flaws in the RCTs included in the review. Consistency point deducted for conflicting results
2 (1828) Symptom improvement Antispasmodic drugs versus placebo 4 –2 –1 0 0 Very low Quality points deducted for short follow-up and heterogeneity of trials. Consistency point deducted for different results with different drugs in the same class
4 (392) Symptom improvement Peppermint oil versus placebo 4 –2 0 0 0 Low Quality points deducted for short follow-up and methodological flaws in the RCTs included in the review
6 (321) Symptom improvement Soluble fibre versus placebo 4 –3 0 0 0 Very low Quality points deducted for short follow-up, heterogeneity of studies, and other methodological flaws in the RCTs included in the review
5 (221) Symptom improvement Insoluble fibre versus placebo 4 –2 0 0 0 Low Quality points deducted for short follow-up and other methodological flaws in the RCTs included in the review
11 (9242) Symptom improvement Tegaserod versus placebo 4 –2 0 –1 0 Very low Quality points deducted for short follow-up and heterogeneity of studies. Directness point deducted for uncertainty about generalisability of results
8 (4987) Symptom improvement Alosetron versus placebo 4 –2 0 –1 0 Very low Quality points deducted for short follow-up and heterogeneity of studies. Directness point deducted for uncertainty about generalisability of results
1 (623) Symptom improvement Alosetron versus antispasmodic drugs (mebeverine) 4 –2 0 –1 0 Very low Quality points deducted for short follow-up and incomplete reporting of results. Directness point deducted for uncertainty about generalisability of results
1 (539) Symptom improvement Ramosetron versus placebo 4 –2 0 –1 0 Very low Quality points deducted for incomplete reporting of results and short follow-up. Directness point deducted for uncertainty about generalisability of results
18 (at least 566 people) Symptom improvement CBT versus usual care, waiting list control, or placebo 4 –3 –1 0 0 Very low Quality points deducted for short follow-up, incomplete reporting of results, and other methodological flaws in the RCTs included in the review. Consistency point deducted for conflicting results
5 (325) Quality of life CBT versus usual care, waiting list control, or placebo 4 –3 –1 0 0 Very low Quality points deducted for incomplete reporting of results, methodological flaws, and short follow-up. Consistency point deducted for conflicting results
3 (121) Symptom improvement Hypnotherapy versus no hypnotherapy 4 –2 –1 –1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for population restricted to people who had not responded to conventional treatments. Consistency point deducted for different results at different time points
1 (81) Quality of life Hypnotherapy versus no hypnotherapy 4 –2 0 –1 0 Very low Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for population restricted to people who had not responded to conventional treatments
5 (214) Symptom improvement Loperamide versus placebo 4 –3 –1 0 0 Very low Quality points deducted for short follow-up, incomplete reporting of results, and other methodological flaws. Consistency point deducted for conflicting results
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We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Contributor Information

Alexander Charles Ford, Department of Academic Medicine, St. James's University Hospital, Leeds, UK.

Per Olav Vandvik, Innlandet Hospital Trust, Gjovik, Norway.

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BMJ Clin Evid. 2010 Jan 5;2010:0410.

Antidepressants

Summary

Antidepressants (tricyclic antidepressants and SSRIs) may reduce global symptoms of IBS and abdominal pain compared with placebo.

Benefits and harms

Antidepressants versus placebo:

We found two systematic reviews (search date 2007, 5 RCTs, 221 people; search date 2008, 13 RCTs [7 RCTs used standard diagnostic criteria for IBS], 789 people) and one subsequent RCT. The reviews identified five RCTs (221 people) in common, but they performed different meta-analyses and reached different conclusions, so we report the results of both here (see further information on studies). The harms of SSRI and tricyclic antidepressants are well known; see review on Depression in adults: drug and physical treatments.

Symptom improvement

Antidepressants compared with placebo Tricyclic antidepressants may be more effective than placebo at improving global symptoms or abdominal pain in IBS, but we don't know whether SSRIs are more effective than placebo (very low-quality evidence)

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 204 people
4 RCTs in this analysis		 Proportion of people with improved abdominal pain
49/105 (47%) with SSRIs (fluoxetine, paroxetine, and citalopram)
26/99 (26%) with placebo
OR 4.68
95% CI 0.64 to 34.3 		Not significant

Systematic review		 132 people
3 RCTs in this analysis		 Proportion of people with improved bloating
26/62 (42%) with SSRIs (fluoxetine, paroxetine, and citalopram)
18/70 (26%) with placebo
OR 2.46
95% CI 0.40 to 15.2 		Not significant

Systematic review		 73 people
2 RCTs in this analysis		 Proportion of people with improved global symptoms
22/36 (61%) with SSRIs (fluoxetine, paroxetine, and citalopram)
20/37 (54%) with placebo
OR 1.31
95% CI 0.50 to 3.39 		Not significant

Systematic review		 789 people
13 RCTs in this analysis		 Proportion of people with persistent symptoms
182/432 (42%) with antidepressants
231/357 (65%) with placebo
RR 0.66
95% CI 0.57 to 0.78
NNT 4
95% CI 3 to 6 		Small effect size antidepressant therapy

Systematic review		 575 people
9 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
132/319 (41%) with tricyclic antidepressants
153/256 (60%) with placebo
RR 0.68
95% CI 0.56 to 0.83
NNT 4,
95% CI 3 to 8
Statistically significant heterogeneity (defined as I2 value >25%; P <0.10) between studies (I2 = 26.9%; P = 0.21). There were insufficient studies available to explore reasons for this heterogeneity 		Small effect size tricyclic antidepressants

Systematic review		 230 people
5 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
50/113 (44%) with SSRIs
83/117 (71%) with placebo
RR 0.62
95% CI 0.45 to 0.87
NNT 3.5
95% CI 2 to 14
Statistically significant heterogeneity (defined as I2 value >25%; P <0.10) between studies (I2 = 38.1%; P = 0.17). There were insufficient studies available to explore reasons for this heterogeneity 		Small effect size SSRIs

RCT		 72 people with IBS (Rome II criteria) Reduction in self-reported composite pain scores (scale of 1−9 with 1 = mild pain/discomfort, 9 = very severe pain/discomfort) 12 weeks
–2.8 with paroxetine
–1.9 with placebo
P = 0.82 		Not significant

RCT		 72 people with IBS (Rome II criteria) Proportion of treatment responders (response defined as a score of 1 or 2 on the Clinical Global Impression-Improvement scale [scale not further defined] after treatment) 12 weeks
25/36 (69%) with paroxetine
6/36 (17%) with placebo
P <0.01 		Effect size not calculated paroxetine
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 301 people
6 RCTs in this analysis		 Proportion of people with adverse effects
27/149 (18%) with antidepressants
14/152 (9%) with placebo
RR 1.63
95% CI 0.94 to 2.80 		Not significant

RCT		 72 people with IBS (Rome II criteria) Any individual adverse effect
with paroxetine
with placebo		 Not significant

RCT		 72 people with IBS (Rome II criteria) Drowsiness
13/36 (36%) with paroxetine
9/36 (25%) with placebo
Reported as not significant
P value not reported 		Not significant

RCT		 72 people with IBS (Rome II criteria) Dry mouth
10/36 (28%) with paroxetine
6/36 (17%) with placebo
Reported as not significant
P value not reported 		Not significant
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No data from the following reference on this outcome.

Further information on studies

One of the RCTs identified by the two reviews was a crossover study comparing SSRIs with placebo, and was handled differently by both reviews. The authors of the first review used post-crossover results, whereas the authors of the second review used pre-crossover results (obtained by contacting the authors of the RCT). This may partly explain the reason for the difference in efficacy of SSRIs in IBS reported by the two reviews. Four studies in the second systematic review adjusted for the effects of antidepressants on underlying depression, which could account for some of their benefits in people with IBS, and none demonstrated any correlation between improvement in depression scores and improvement in IBS symptoms.

Comment

None of the trials identified by the review was conducted in primary care. RCTs were not of sufficient duration to determine whether the benefits of antidepressants remain in the long term.

Substantive changes

Antidepressants Two systematic reviews and one RCT added. The two reviews supersede three older systematic reviews previously reported in this Clinical Evidence review, which included some of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

Antispasmodics

Summary

Antispasmodic drugs and peppermint oil may reduce global symptoms of IBS and abdominal pain compared with placebo.

Mebeverine may be less likely than alosetron to cause constipation.

Benefits and harms

Antispasmodic drugs versus placebo:

We found one systematic review (search date 2008; 22 RCTs, 1778 people) and one additional RCT.

Symptom improvement

Antispasmodic drugs compared with placebo Some antispasmodic drugs (otilonium, cimetropium, hyoscine, pinaverium, and dicycloverine) may be more effective than placebo at improving global symptoms or abdominal pain in IBS. However, we don't know whether trimebutine, mebeverine, pirenzipine, prifinium, propinox, rociverine, and alverine are more effective than placebo (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 1778 people
22 RCTs in this analysis		 Proportion of people with persistent symptoms
350/905 (39%) with antispasmodics (otilonium, cimetropium, hyoscine, pinaverium, trimebutine, rociverine, alverine, dicycloverine, mebeverine, pirenzipine, prifinium, and propinox)
485/873 (56%) with placebo
RR 0.68
95% CI 0.57 to 0.81
NNT 5
95% CI 4 to 9
Statistically significant heterogeneity (defined as I2 >25%; P <0.10) between RCTs (I2 = 62.6%; P <0.001)
In a subgroup analysis of high-quality studies, heterogeneity persisted (I2 = 70.2%; P = 0.0001) 		Small effect size antispasmodics

Systematic review		 435 people
4 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
111/216 (51%) with otilonium
155/219 (71%) with placebo
RR 0.55
95% CI 0.31 to 0.97 		Small effect size otilonium

Systematic review		 158 people
3 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
15/79 (19%) with cimetropium
42/79 (53%) with placebo
RR 0.38
95% CI 0.20 to 0.71 		Moderate effect size cimetropium

Systematic review		 426 people
3 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
63/215 (29%) with hyoscine
97/211 (46%) with placebo
RR 0.63
95% CI 0.51 to 0.78 		Small effect size hyoscine

Systematic review		 188 people
3 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
26/94 (28%) with pinaverium
57/94 (61%) with placebo
RR 0.47
95% CI 0.33 to 0.67 		Moderate effect size pinaverium

Systematic review		 97 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
21/48 (44%) with dicycloverine
33/49 (67%) with placebo
RR 0.65
95% CI 0.45 to 0.95 		Small effect size dicycloverine

Systematic review		 140 people
3 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
28/70 (40%) with trimebutine
27/70 (39%) with placebo
RR 1.08
95% CI 0.72 to 1.61 		Not significant

Systematic review		 80 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
35/40 (88%) with mebeverine
28/40 (70%) with placebo
RR 1.25
95% CI 0.99 to 1.58 		Not significant

Systematic review		 24 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
7/12 (58%) with pirenzipine
6/12 (50%) with placebo
RR 1.17
95% CI 0.56 to 2.45 		Not significant

Systematic review		 18 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
3/9 (33%) with prifinium
6/9 (67%) with placebo
RR 0.50
95% CI 0.18 to 1.40
The RCT is likely to have been underpowered to detect a clinically important difference between groups 		Not significant

Systematic review		 75 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
4/39 (10%) with propinox
3/36 (8%) with placebo
RR 1.23
95% CI 0.30 to 5.13 		Not significant

Systematic review		 60 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
11/30 (37%) with rociverine
10/30 (33%) with placebo
RR 1.10
95% CI 0.55 to 2.19 		Not significant

Systematic review		 107 people
Data from 1 RCT
Subgroup analysis		 Proportion of people with persistent symptoms
26/53 (49%) with alverine
31/54 (57%) with placebo
RR 0.85
95% CI 0.60 to 1.22 		Not significant

RCT		 50 people with IBS (Rome II criteria) Participant satisfaction (assessed on a visual analogue scale of 1−10, with higher scores indicating greater satisfaction) 2 weeks
8.1 with trimebutine
5.2 with placebo
P <0.01 		Effect size not calculated trimebutine
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 1379 people
13 RCTs in this analysis		 Proportion of people reporting adverse effects
101/704 (14%) with antispasmodics (otilonium, cimetropium, hyoscine, pinaverium, trimebutine, rociverine, alverine, dicycloverine, mebeverine, pirenzipine, prifinium, and propinox)
62/675 (9%) with placebo
RR 1.62
95% CI 1.05 to 2.50 		Small effect size placebo
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No data from the following reference on this outcome.

Peppermint oil versus placebo:

We found one systematic review (search date 2008; 4 RCTs, 392 people).

Symptom improvement

Peppermint oil compared with placebo Peppermint oil may be more effective than placebo at improving global symptoms or abdominal pain in IBS (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 392 people
4 RCTs in this analysis		 Proportion of people with persistent symptoms
52/197 (26%) with peppermint oil
127/195 (65%) with placebo
RR 0.43
95% CI 0.32 to 0.59
NNT 2.5
95% CI 2 to 3
Statistically significant heterogeneity (defined as I2 >25%; P <0.10) between RCTs (I2 = 31.1%; P = 0.23) 		Moderate effect size peppermint oil

Systematic review		 Number of people not reported
3 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
with peppermint oil
with placebo
Absolute results not reported
RR 0.40
95% CI 0.29 to 0.55
Heterogeneity was no longer significant in a subgroup analysis of high-quality studies (I2 = 22.0%; P = 0.28) 		Moderate effect size peppermint oil
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 345 people
3 RCTs in this analysis		 Proportion of people reporting adverse effects
5/174 (3%) with peppermint oil
0/171 (0%) with placebo
Significance not reported
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Antispasmodics versus 5HT3 receptor antagonists:

See benefits of 5HT3 antagonists (alosetron).

Further information on studies

Only two of the studies included in the review were conducted in primary care. Included RCTs were of insufficient duration to determine whether the benefits of antispasmodics or peppermint oil remain in the long term. The large variety of drugs used in the meta-analysis also make it difficult to assess whether the effect seen is a true class-effect of antispasmodics.

Comment

None.

Substantive changes

Antispasmodics One systematic review and one RCT added. The review supersedes two older systematic reviews previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

Soluble fibre supplementation

Summary

Soluble fibre supplementation may reduce global symptoms of IBS and abdominal pain compared with placebo.

Benefits and harms

Soluble fibre versus placebo:

We found one systematic review (search date 2008; 6 RCTs, 321 people with IBS) comparing ispaghula with placebo.

Symptom improvement

Soluble fibre compared with placebo We don't know whether soluble fibre (ispaghula) is more effective than placebo at improving global symptoms or abdominal pain in IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 321 people
6 RCTs in this analysis		 Proportion of people with persistent symptoms
83/161 (52%) with soluble fibre
103/160 (64%) with placebo
RR 0.78
95% CI 0.63 to 0.96
NNT 6
95% CI 3 to 50
Statistically significant heterogeneity (defined as I2 >25%; P <0.10) between RCTs (I2 = 34.4%; P = 0.18) 		Small effect size soluble fibre

Systematic review		 Number of people not reported
5 RCTs in this analysis
Subgroup analysis		 Proportion of people with persistent symptoms
with soluble fibre
with placebo
Absolute results not reported
RR 0.86
95% CI 0.74 to 1.01
P = 0.06
Heterogeneity was no longer significant in a subgroup analysis of high-quality studies (I2 = 2.6%; P = 0.39) 		Not significant
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Quality of life

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The review did not report on specific adverse effects of ispaghula, owing to a lack of reporting of these in included RCTs.

Comment

None of the studies included in the review was conducted in primary care. Included RCTs were of insufficient duration to determine whether the benefits of soluble fibre remain in the long term.

Substantive changes

Soluble fibre supplementation One systematic review added. This supersedes an older systematic review previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Likely to be beneficial).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

Insoluble fibre supplementation

Summary

Insoluble fibre supplementation does not reduce global symptoms of IBS or abdominal pain compared with placebo, but we found no evidence from RCTs that it exacerbates symptoms.

Benefits and harms

Insoluble fibre versus placebo:

We found one systematic review (search date 2008; 5 RCTs, 221 people with IBS) comparing dietary supplementation with bran versus control (placebo dietary supplementation or low-fibre diet).

Symptom improvement

Insoluble fibre compared with placebo Insoluble fibre (wheat bran) may be no more effective than placebo at improving global symptoms or abdominal pain in IBS (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 221 people
5 RCTs in this analysis		 Proportion of people with persistent symptoms
62/114 (54%) with insoluble fibre (bran)
58/107 (54%) with placebo
RR 1.02
95% CI 0.82 to 1.27
No statistically significant heterogeneity (defined as I2 >25%; P <0.10) 		Not significant
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Quality of life

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The review did not report on specific adverse effects of bran, owing to a lack of reporting of these in included RCTs.

Comment

None of the studies included in the review was conducted in primary care. Some investigators have reported that insoluble fibre worsens pain and bloating in IBS, but the trials included in the systematic review did not report data in such a way that this issue could be examined.

Substantive changes

Insoluble fibre supplementation One systematic review added. This supersedes an older systematic review previously reported in this Clinical Evidence review, which included many of the same studies and reached similar conclusions. Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

5HT4 receptor agonists

Summary

The 5HT 4 receptor agonist tegaserod reduces global symptoms of IBS and abdominal pain compared with placebo in people with constipation-predominant IBS.

A warning has been issued that serious diarrhoea, sometimes requiring hospitalisation, and cerebrovascular and cardiovascular ischaemic events can occur as adverse effects with tegaserod.

Benefits and harms

Tegaserod versus placebo:

We found one systematic review (search date 2008; 11 RCTs, 9242 people [mainly women] with Rome I or Rome II IBS; 8 of these RCTs [7414 people] were only in people with constipation-predominant IBS; 3 of these RCTs [1828 people] excluded people with diarrhoea-predominant IBS) comparing tegaserod (0.5 mg to 12 mg twice daily) versus placebo.

Symptom improvement

Tegaserod compared with placebo Tegaserod may be more effective at improving global symptoms or abdominal pain in people with constipation-predominant IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 9242 people
11 RCTs in this analysis		 Proportion of people with persistent symptoms
3301/6041 (55%) with tegaserod
2032/3201 (64%) with placebo
RR 0.85
95% CI 0.80 to 0.90
NNT 10
95% CI 8 to 14
Statistically significant heterogeneity (defined as I2 >25%; P <0.10) when studies were combined (I2 = 56.7%; P = 0.01), which was not fully explained by subgroup analyses and despite RCTs using standard diagnostic criteria and meeting other recommendations from the Rome committee for the design of RCTs in functional GI disorders 		Small effect size tegaserod
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 2827 people
3 RCTs in this analysis		 Proportion of people with adverse effects
724/1423 (51%) with tegaserod
662/1404 (47%) with placebo
RR 1.07
95% CI 1.00 to 1.15 		Not significant

Systematic review		 6888 people
6 RCTs in this analysis		 Proportion of people with diarrhoea
266/4410 (6%) with tegaserod
51/2478 (2%) with placebo
RR 3.60
95% CI 2.45 to 5.30 		Moderate effect size placebo

Systematic review		 Number of people not reported Proportion of people with cardiovascular events
with tegaserod
with placebo
Absolute results not reported
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5HT4 receptor agonists other than tegaserod versus placebo:

We found no systematic review or RCTs.

Further information on studies

The RCTs included in the systematic review were mainly conducted in women (about 90% of participants), and therefore results may not be generalisable to men with IBS. However, a subgroup analysis by gender in the review demonstrated that tegaserod was also effective in a small number of men. Included RCTs were of insufficient duration to determine whether the benefits of tegaserod remain in the long term.

Comment

A warning has been issued by the FDA about reported cases of cerebrovascular and cardiovascular ischaemic events, as well as severe diarrhoea, in some cases requiring hospitalisation, associated with tegaserod. These adverse effects led to the withdrawal of tegaserod in 2007. However, at the time of this update, it has been reintroduced under an emergency investigational drug protocol.

Substantive changes

5HT4 receptor agonists One systematic review added. This systematic review supersedes two older previously reported reviews, as it reports many of the same RCTs and reaches the same conclusion. Categorisation unchanged (Trade-off between benefits and harms).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

5HT3 receptor antagonists (alosetron)

Summary

Alosetron reduces global symptoms of IBS and abdominal pain in diarrhoea-predominant IBS compared with placebo in women, but we don’t know whether it is effective in men, or whether this effect applies to those with IBS with an alternating bowel habit.

Alosetron may be more effective than mebeverine at reducing symptoms in women with diarrhoea-predominant IBS, but we don't know whether it is effective in men.

Alosetron is associated with constipation, and has been restricted in some countries because of concerns that it may be associated with ischaemic colitis.

Benefits and harms

Alosetron versus placebo:

We found one systematic review (search date 2008; 8 RCTs, 4987 people with Rome I or Rome II IBS; 2 of these RCTs [1367 people] were only in people with diarrhoea-predominant IBS; 4 of these RCTs [2788 people] included at least 70% of people with diarrhoea-predominant IBS) comparing alosetron (0.1 mg to 8 mg twice daily) versus placebo. Five of the identified RCTs (3493 people) included only women, two RCTs included mainly women, and one RCT (626 people) included only men.

Symptom improvement

Alosetron compared with placebo Alosetron may be more effective at improving global symptoms or abdominal pain in women with diarrhoea-predominant IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 4987 people
8 RCTs in this analysis		 Proportion of people with persistent symptoms
1576/3214 (49%) with alosetron
1127/1773 (64%) with placebo
RR 0.79
95% CI 0.69 to 0.90
NNT 8
95% CI 5 to 17
Statistically significant heterogeneity (defined as I2 >25%; P <0.10) among RCTs included in the meta-analysis (I2 = 84.9%; P <0.00001). Not fully explained by subgroup analyses and resulted despite RCTs using standard diagnostic criteria and meeting other recommendations from the Rome committee for the design of RCTs in functional GI disorders 		Small effect size alosetron
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 4607 people
7 RCTs in this analysis		 Proportion of people reporting any adverse effect
1877/2915 (64%) with alosetron
930/1692 (55%) with placebo
RR 1.19
95% CI 1.09 to 1.30 		Small effect size placebo

Systematic review		 Number of people not reported
8 RCTs in this analysis		 Proportion of people reporting any adverse effect
716 (25%) with alosetron
96 (6%) with placebo
Absolute numbers not reported
RR 4.50
95% CI 3.11 to 6.53 		Moderate effect size placebo

Systematic review		 3498 people
5 RCTs in this analysis		 Proportion of people with serious adverse effects
66/2246 (2.9%) with alosetron
30/1252 (2.4%) with placebo
RR 1.30
95% CI 0.83 to 2.04 		Not significant

Systematic review		 Number of people not reported Proportion of people with ischaemic colitis
with alosetron
with placebo
Absolute results not reported
Four people developed ischaemic colitis with alosetron (total number of people, absolute risk, or significance assessment not reported). Alosetron has been associated with cases of ischaemic colitis, as well as severe constipation; see comment
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Alosetron versus antispasmodic drugs (mebeverine):

We found one systematic review (1 RCT; 623 people, all women; mainly [>70%] diarrhoea-predominant IBS; see comment below).

Symptom improvement

Alosetron compared with mebeverine Alosetron may be more effective at reducing symptoms in women with diarrhoea-predominant IBS compared with the antispasmodic drug mebeverine (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 623 people
Data from 1 RCT		 Symptoms (pain, discomfort, stool frequency and consistency) 12 weeks
with alosetron (2 mg/day or more)
with mebeverine
Absolute results not reported
OR 1.69
95% CI 1.42 to 2.32 		Small effect size alosetron
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 623 people
Data from 1 RCT		 Constipation
with alosetron (2 mg/day or more)
with mebeverine
Absolute results not reported
OR 10.59
95% CI 9.15 to 12.25 		Large effect size mebeverine

Systematic review		 623 people
Data from 1 RCT		 Overall adverse effects
with alosetron (2 mg/day or more)
with mebeverine
Absolute results not reported
OR 1.22, 95% CI 0.87 to 1.69 		Not significant
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Alosetron versus antispasmodics other than mebeverine:

We found no systematic review or RCTs.

Further information on studies

The efficacy of alosetron in men is unclear because most participants in the RCTs included in the reviews were women. Only one RCT used alosetron for more than 12 weeks, so it is unclear if the benefits remain in the long term.

Comment

Alosetron has been associated with cases of ischaemic colitis, as well as severe constipation, in some cases requiring hospitalisation. These adverse effects led to the withdrawal of alosetron in 2000. However, it has since been reintroduced, with its use regulated by an FDA prescribing programme.

Substantive changes

5HT3 receptor antagonists: One systematic review added comparing alosetron versus placebo. It pooled results from five RCTs previously reported in this Clinical Evidence review and three subsequent RCTs. It found that alosetron significantly improved global symptoms or abdominal pain compared with placebo. Categorisation unchanged (Trade-off between benefits and harms).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

5HT3 receptor antagonists other than alosetron

Summary

Ramosetron may reduce global symptoms of IBS and abdominal pain, and improve abnormal bowel habits, compared with placebo in people with diarrhoea-predominant IBS.

Benefits and harms

Ramosetron versus placebo:

We found one RCT (539 people, predominantly men, with Rome II diarrhoea-predominant IBS) comparing ramosetron versus placebo.

Symptom improvement

Ramosetron compared with placebo Ramosetron may be more effective at reducing symptoms in diarrhoea-predominant IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

RCT		 539 people Proportion of people with response to treatment 12 weeks
47% with ramosetron
27% with placebo
Absolute numbers not reported
P <0.001 		Effect size not calculated ramosetron

RCT		 539 people Proportion of people reporting relief of abdominal pain or discomfort 12 weeks
46% with ramosetron
33% with placebo
Absolute numbers not reported
P = 0.005 		Effect size not calculated ramosetron

RCT		 539 people Proportion of people reporting improvement in abnormal bowel habits 12 weeks
44% with ramosetron
24% with placebo
Absolute numbers not reported
P <0.001 		Effect size not calculated ramosetron
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 539 people Proportion of people reporting adverse effects
163/270 (60%) with ramosetron
141/269 (52%) with placebo
P = 0.08 		Not significant

RCT		 539 people Hard stools
20/270 (7%) with ramosetron
2/269 (1%) with placebo
P <0.001 		Effect size not calculated placebo

RCT		 539 people Discontinued treatment due to adverse effects
13/270 (5%) with ramosetron
10/269 (4%) with placebo
Significance assessment not reported
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Further information on studies

None.

Comment

Ramosetron is not currently available in the USA or Europe. Further data are required to confirm the beneficial effect of ramosetron in diarrhoea-predominant IBS.

Another 5HT3 receptor antagonist, cilansetron, has been studied, but it is not licensed for use in IBS at the time of writing this review. We found one systematic review (search date 2008; 3 RCTs [all published as abstracts only], 2229 people with Rome criteria-defined diarrhoea-predominant IBS) comparing cilansetron with placebo. It found that cilansetron (6 mg/day) significantly improved global symptoms or abdominal pain compared with placebo (proportion of people with persistent symptoms: 542/1116 [49%] with cilansetron v 721/1113 [65%] with placebo; RR 0.75, 95% CI 0.69 to 0.82; NNT 6, 95% CI 5 to 8). Although there appeared to be a treatment effect in favour of cilansetron in the systematic review, all three RCTs were reported in abstract form only, and they did not report adverse effects data. Only one RCT used cilansetron for more than 12 weeks, so it is unclear if the benefits remain in the long term.

Substantive changes

5HT3 receptor antagonists other than alosetron (ramosetron) One RCT added. It found that ramosetron increased response to treatment and patient-reported relief of abdominal pain or discomfort and improvement in abnormal bowel habits compared with placebo after 12 weeks' treatment. Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

CBT

Summary

CBT may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term. We don't know whether it is beneficial in the longer term.

Benefits and harms

CBT versus usual care, waiting list control, or placebo:

We found two systematic reviews (both search dates 2008) and one subsequent RCT. The first systematic review (7 RCTs, 491 people) compared CBT versus control therapy or physician’s usual management. The second systematic review (17 RCTs) compared CBT (cognitive treatment in 4 RCTs; behavioural treatment in 7 RCTs; and a combination of cognitive and behavioural therapy in 6 RCTs) with physician’s usual care (not defined) or placebo. The two reviews identified seven RCTs (491 people) in common; however, they applied different inclusion/exclusion criteria and performed different meta-analyses, so we report both here. The subsequent RCT (75 people with Rome II-diagnosed IBS, 65 [86%] women) was a three-arm trial comparing self-administered CBT versus therapist-administered CBT versus waiting list control for 10 weeks.

Symptom improvement

CBT compared with usual care, waiting list control, or placebo CBT may be more effective at improving global symptoms or abdominal pain in IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 491 people
7 RCTs in this analysis		 Proportion of people with persistent symptoms
118/279 (42%) with CBT
130/212 (61%) with control therapy or physician’s usual management
RR 0.60
95% CI 0.42 to 0.87
NNT 3
95% CI, 2 to 7
Statistically significant heterogeneity (defined as I2 value >25%; P <0.10) between studies when pooled (I2 = 70.7%; P = 0.002). No obvious explanations for heterogeneity.
Evidence of publication bias, or other small study effects (Egger test for funnel plot asymmetry; P = 0.01). 		Small effect size CBT

Systematic review		 133 people
4 RCTs in this analysis		 Symptom scores 2 months
with CBT
with usual care
SMD 0.75
95% CI –0.20 to +1.70 		Not significant

Systematic review		 378 people
5 RCTs in this analysis		 Symptom scores 3 months
with CBT
with usual care
SMD +0.58
95% CI 0.36 to 0.79 		Effect size not calculated CBT

Systematic review		 80 people
3 RCTs in this analysis		 Improvement of abdominal pain 2 months
with CBT
with usual care
SMD 0.45
95% CI 0 to 0.91 		Not significant

Systematic review		 359 people
7 RCTs in this analysis		 Improvement of abdominal pain 2 months
with CBT
with usual care
SMD +0.22
95% CI –0.04 to +0.49 		Not significant

Systematic review		 44 people
2 RCTs in this analysis		 Symptom scores 2 months
with CBT
with placebo
SMD +0.68
95% CI –0.01 to +1.36 		Not significant

Systematic review		 230 people
3 RCTs in this analysis		 Symptom scores 3 months
with CBT
with placebo
SMD –0.17
95% CI –0.45 to +0.11 		Not significant

Systematic review		 20 people
Data from 1 RCT		 Improvement of abdominal pain 2 months
with CBT
with placebo
SMD –0.41
95% CI –1.30 to +0.48 		Not significant

Systematic review		 395 people
5 RCTs in this analysis		 Improvement of abdominal pain 3 months
with CBT
with placebo
SMD +0.33
95% CI –0.16 to +0.82 		Not significant

RCT
3-armed trial 		75 people Proportion of people reporting adequate relief from pain and bowel symptoms 12 weeks
72% with self-administered CBT for 10 weeks
7% with waiting list control for 10 weeks
Absolute numbers not reported
P <0.05 		Effect size not calculated self-administered CBT

RCT
3-armed trial 		75 people Proportion of people reporting adequate relief from pain and bowel symptoms 12 weeks
61% with therapist-administered CBT for 10 weeks
7% with waiting list control for 10 weeks
Absolute numbers not reported
P <0.05 		Effect size not calculated therapist-administered CBT

RCT
3-armed trial 		75 people Mean improvement in global symptom score 12 weeks
1.68 with self-administered CBT for 10 weeks
0.11 with waiting list control for 10 weeks
P <0.05 		Effect size not calculated self-administered CBT

RCT
3-armed trial 		75 people Mean improvement in global symptom score 12 weeks
1.56 with therapist-administered CBT for 10 weeks
0.11 with waiting list control for 10 weeks
P <0.05 		Effect size not calculated therapist-administered CBT
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Quality of life

CBT compared with usual care or placebo CBT may be more effective at improving quality-of-life scores (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Quality of life

Systematic review		 97 people
2 RCTs in this analysis		 Quality of life 2 months
with CBT
with usual care
SMD 0.44
95% CI 0.04 to 0.85 		Effect size not calculated CBT

Systematic review		 24 people
Data from 1 RCT		 Quality of life 3 months
with CBT
with usual care
SMD 0.92
95% CI 0.07 to 1.77 		Effect size not calculated CBT

Systematic review		 129 people
Data from 1 RCT		 Quality of life 3 months
with CBT
with placebo
SMD –0.16
95% CI –0.22 to +0.54 		Not significant

RCT
3-armed trial 		75 people Mean score on IBS quality of life questionnaire (change from baseline) 12 weeks
58.7 to 78.3 with self-administered CBT for 10 weeks
62.0 to 64.2 with waiting list control for 10 weeks
P <0.05 		Effect size not calculated self-administered CBT

RCT
3-armed trial 		75 people Mean score on IBS quality of life questionnaire (change from baseline) 12 weeks
52.0 to 72.0 with therapist-administered CBT for 10 weeks
62.0 to 64.2 with waiting list control for 10 weeks
P <0.05 		Effect size not calculated therapist-administered CBT
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No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

There are several possible explanations as to why the systematic reviews reached different conclusions regarding the effectiveness of CBT in IBS. Both included a variety of psychological interventions in addition to CBT, and differed in their selection criteria and definitions for interventions and outcomes. The second systematic review performed meta-analyses for three different outcomes for symptoms of IBS and for two different control groups, suggesting type II error as a possible explanation for the non-significant effect of CBT in the meta-analysis. Three of seven studies in the first systematic review were conducted in the same centre. When these three studies were excluded from the analysis, the beneficial effect of CBT on global symptoms of IBS disappeared (RR 0.79, 95% CI 0.56 to 1.13).

Comment

Other outcomes important to people with IBS, such as functional disability and adverse events, were poorly reported in the identified literature.

Substantive changes

CBT Two systematic reviews and one RCT added. These supersede three older previously reported systematic reviews, as they provided more information, included many of the same studies, and reached similar conclusions. Categorisation changed from Unknown effectiveness to Likely to be beneficial.

BMJ Clin Evid. 2010 Jan 5;2010:0410.

Hypnotherapy

Summary

Hypnotherapy may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term.

Benefits and harms

Hypnotherapy versus no hypnotherapy:

We found two systematic reviews (search dates 2006 and 2008). The first systematic review did not perform a meta-analysis. There was crossover between the two reviews in terms of the RCTs identified. Therefore we only report the results of the second systematic review, and we report separately one additional RCT from the first review that met Clinical Evidence inclusion criteria.

Symptom improvement

Hypnotherapy compared with no hypnotherapy We don't know whether hypnotherapy is more effective at improving symptoms in people with IBS most of whom had not responded to conventional treatment (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

Systematic review		 40 people
2 RCTs in this analysis		 Proportion of people with persistent symptoms
7/20 (35%) with hypnotherapy
15/20 (75%) with control therapy or physician’s usual management
RR 0.48
95% CI 0.26 to 0.87
NNT 2
95% CI 1.5 to 17 		Moderate effect size hypnotherapy

RCT		 81 people in primary care whose IBS symptoms had not responded to conventional treatments Mean improvement in overall symptom score (based on Rome II criteria, endpoints not clear) 3 months
13.0 with five 30-minute hypnotherapy sessions plus daily autohypnosis tape plus standard care
4.5 with standard care alone
P = 0.008 		Effect size not calculated hypnotherapy

RCT		 81 people in primary care whose IBS symptoms had not responded to conventional treatments Mean improvement in overall symptom score (based on Rome II criteria, endpoints not clear) 12 months
9.1 with five 30-minute hypnotherapy sessions plus daily autohypnosis tape plus standard care
6.4 with standard care alone
P = 0.44 		Not significant
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Quality of life

Hypnotherapy compared with no hypnotherapy We don't know whether hypnotherapy is more effective than no hypnotherapy at improving quality-of-life measures on an IBS-specific scale in people with IBS who had not responded to conventional treatments (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Quality of life

RCT		 81 people in primary care whose IBS symptoms had not responded to conventional treatments Mean improvement in quality-of-life scores (measured on an IBS-specific scale, endpoints not clear) 3 months
10.1 with five 30-minute hypnotherapy sessions plus daily autohypnosis tape plus standard care
3.9 with standard care alone
P = 0.11 		Not significant

RCT		 81 people in primary care whose IBS symptoms had not responded to conventional treatments Mean improvement in quality-of-life scores (measured on an IBS-specific scale, endpoints not clear) 12 months
13.6 with five 30-minute hypnotherapy sessions plus daily autohypnosis tape plus standard care
10.9 with standard care alone
P = 0.24 		Not significant
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No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Most studies are performed in small numbers of participants in secondary care, often with resistant symptoms and high psychosocial burden. The RCT performed in a primary care setting indicated that the initial beneficial effect of hypnotherapy did not last. Both RCTs used a gut-directed hypnotherapy protocol.

Comment

None.

Substantive changes

Hypnotherapy Two systematic reviews added. These supersede a previously reported early narrative systematic review as they include some of the same studies, provide more information, and reach similar conclusions. One of the new systematic reviews carried out a meta-analysis and found that hypnotherapy reduced global symptoms or abdominal pain compared with placebo. Categorisation changed (from Unknown effectiveness to Likely to be beneficial).

BMJ Clin Evid. 2010 Jan 5;2010:0410.

Loperamide

Summary

Loperamide may reduce stool frequency in diarrhoea-predominant IBS, but it may not improve other symptoms compared with placebo.

Benefits and harms

Loperamide versus placebo:

We found one systematic review (search date 2004) identifying five poor-quality RCTs (see comment). It did not pool data. The fifth crossover RCT (11 people) included two people without IBS, and all included participants had chronic diarrhoea plus faecal incontinence; we have not reported this RCT further here.

Symptom improvement

Loperamide compared with placebo Loperamide may be no more effective at reducing symptoms of IBS, but it may decrease stool frequency in people with diarrhoea-predominant IBS (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom improvement

RCT
Crossover design 		28 people; symptoms suggestive of IBS for at least 6 months and failed to respond to 4-week trial of dietary bran Stool frequency and urgency
with loperamide
with placebo
Reported as significant 		Effect size not calculated loperamide

RCT
Crossover design 		28 people; symptoms suggestive of IBS for at least 6 months and failed to respond to 4-week trial of dietary bran Global IBS symptoms or pain
with loperamide
with placebo
Reported as not significant 		Not significant

RCT		 16 people with IBS (painless diarrhoea)
Subgroup analysis		 Stool frequency and consistency
with loperamide
with placebo
P <0.01 		Effect size not calculated loperamide

RCT		 21 people with IBS (alternating bowel habit with pain)
Subgroup analysis		 Stool frequency and consistency
with loperamide
with placebo
P <0.02 		Effect size not calculated loperamide

RCT		 12 people with IBS (alternating bowel habit without pain)
Subgroup analysis		 Stool frequency and consistency
with loperamide
with placebo
Reported as not significant; P value not reported 		Not significant

RCT		 9 people with IBS (constipation)
Subgroup analysis		 Stool frequency and consistency
with loperamide
with placebo
Reported as not significant; P value not reported 		Not significant

RCT		 90 people Stool frequency
with loperamide
with placebo
P <0.05 		Effect size not calculated loperamide

RCT		 90 people Stool consistency
with loperamide
with placebo
P <0.05 		Effect size not calculated loperamide

RCT		 90 people Abdominal pain
with loperamide
with placebo
Reported as not significiant; P value not reported 		Not significant

RCT		 25 people with diarrhoea-predominant IBS Stool consistency
with loperamide
with placebo
P <0.001 		Effect size not calculated loperamide

RCT		 25 people with diarrhoea-predominant IBS Global symptom improvement
with loperamide
with placebo
P <0.03 		Effect size not calculated loperamide

RCT		 25 people with diarrhoea-predominant IBS Urgency
with loperamide
with placebo
P <0.05 		Effect size not calculated loperamide

RCT		 25 people with diarrhoea-predominant IBS Pain
with loperamide
with placebo
P <0.05 		Effect size not calculated loperamide
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Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT
Crossover design 		28 people; symptoms suggestive of IBS for at least 6 months and failed to respond to 4-week trial of dietary bran Adverse effects
29% with loperamide
36% with placebo
Absolute numbers not reported
Statistical analysis not reported; no further details provided

RCT		 60 people with IBS Adverse effects
with loperamide
with placebo

RCT		 90 people Adverse effects
with loperamide
with placebo
P <0.05 		Effect size not calculated placebo

RCT		 25 people with diarrhoea-predominant IBS Proportion of people with adverse effects
with loperamide
with placebo
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Further information on studies

The authors of the review conclude that there is excellent evidence for the antidiarrhoeal effect of loperamide in diarrhoea-predominant IBS.

Comment

The conclusions of the review described above are in line with those of an earlier review (search date 2001; 3 RCTs identified; no meta-analysis). However, all but one RCT in these two reviews are more than 10 years old, and do not meet basic methodological quality standard criteria for functional GI disease research. The RCTs did not use the Rome criteria for inclusion, did not present sample-size calculations, all but one had a follow-up of less than 12 weeks, and none used a validated symptom score. The significance of their findings should be viewed with caution.

Substantive changes

No new evidence

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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