Assessing the evidence

We found 156 studies through surveillance of this guideline.

This included evidence suggesting possible effects of ondansetron and dietary supplements such as vitamin D and a herbal medicine combination of fennel oil plus curcumin. We asked topic experts whether this evidence would affect current recommendations. Generally, the topic experts thought that an update of these areas was not needed.

We also identified evidence that supports current recommendations on:

• diagnosis of irritable bowel syndrome, including evidence that supports NICE diagnostic guidance on SeHCAT (tauroselcholic [75 selenium] acid) testing for bile acid malabsorption and on faecal calprotectin testing
• low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, other exclusion diets, dietary supplements and probiotics
• physical activity interventions
• drug treatments including antispasmodics, laxatives, antidepressants
• psychological therapies such as cognitive behavioural therapy (CBT)
• alternative therapies, for example, hypnotherapy, biofeedback, relaxation, acupuncture and herbal medicine.

We found evidence on serotonin 5-HT3 and 5-HT4 receptor antagonists, which was not covered in the guideline. However, the evidence was insufficient to add new recommendations in this area at this time.

For any new evidence relating to published or ongoing NICE technology appraisals, the guideline surveillance review deferred to the technology appraisal decision. This included a study of eluxadoline, which is currently being evaluated, and technology appraisal guidance is expected in 2017.

Equalities

No equalities issues were identified during the surveillance process.

Overall decision

After considering all the evidence and views of topic experts and stakeholders, we decided that no update is necessary for this guideline.

See how we made the decision for further information.

What the guideline recommends

The irritable bowel syndrome guideline recommends that healthcare professionals should consider prescribing antispasmodic agents for people with IBS. These should be taken as required, alongside dietary and lifestyle advice. Alverine is an antispasmodic. The guideline has no recommendations on simeticone. However, this anti-foaming agent is available on general sale in the UK, marketed for the relief of symptoms of gastrointestinal gas. No combination products containing both treatments are available in the UK.

Methods

Ducrotte et al. (2013) conducted a pragmatic randomised controlled trial (RCT; n=436) in adults with moderate to severe IBS symptoms (IBS symptom severity score of 175 to 400) lasting between 1 year and 10 years. GPs (n=87) in France were randomly assigned to prescribe either on-demand alverine 60 mg plus simeticone 300 mg or to the physician’s choice of usual treatment. The randomisation of physicians rather than patients was designed to avoid possible investigator bias that could arise if a GP treated both groups of patients.

In the on-demand alverine plus simeticone group, participants were instructed to take the treatment 3 times daily, before meals, until the end of the pain episode. In the usual care group, physicians were not allowed to prescribe alverine plus simeticone, but prescribed what they considered to be the most appropriate treatment, which could include antispasmodics. Irritant laxatives were not allowed for treatment of constipation in either group.

The primary endpoint was the change in total IBS quality-of-life score (measured by IBSQoL) after 6 months. Secondary endpoints included individual IBSQoL domains and change in symptom severity. Exclusion criteria were digestive disorders with organic or other causes, untreated endocrine disorders, or neurological disease. People were also excluded if they were treated with alverine plus simethicone in the 6 months before the study.

Results

The mean age of participants was 54 years and 73% were women. Participants had a mean duration of IBS of 6 years and a median of 5 abdominal pain episodes per year. In the usual treatment group, 58% were prescribed 1 treatment, 31% were prescribed 2 treatments and 9% were prescribed at least 3 treatments. Most people were prescribed an antispasmodic (94%), with 20% of people prescribed a laxative, 3% prescribed analgesics and 2% prescribed bulking agents.

The mean change in IBSQoL score (adjusted for baseline value) over 6 months was 13.8 in the alverine plus simeticone group compared with 8.4 in the usual care group. The between-group difference was therefore 5.4 (95% confidence interval [CI] 2.3 to 8.6, p=0.0008). Most of the individual domains of IBSQoL also showed significant between-group differences, including mental health, sleep, energy, food, and social life, (all p≤0.01). The effects on physical status, physical activity and sexual activity were not reported clearly, although they appear to not have shown significant differences between groups.

Severity of symptoms reduced over the course of the study in both groups, but the reduction was significantly greater in the alverine plus simeticone group than in the usual care group. The between-group difference was −59.3 (95% CI −77.8 to −40.8, p=0.0001).

Adverse events were reported by 41% of people in both groups. The paper reported that no serious adverse events were drug-related, but did not report the number of serious adverse events.

Strengths and limitations

Impact on guideline

The prescription of on-demand alverine is consistent with current recommendations to consider prescribing antispasmodic agents to be taken as needed. Use of simeticone is not currently recommended by the guideline, but an update is not thought to be necessary at this time because simeticone is widely available in the UK without prescription.

What the guideline recommends

The guideline has no recommendations on ondansetron.

Methods

Garsed et al. (2013) conducted a crossover RCT (n=120) in adults (aged 18 to 75 years) with diarrhoea-predominant IBS. Participants were randomly assigned to either ondansetron then placebo for 5 weeks each or to placebo then ondansetron for 5 weeks each. The dosage of ondansetron was 1 or 2 tablets (4 mg per tablet) taken 3 times daily. Participants underwent a 3-week dose titration period at the beginning of each stage of the study, and a 2 to 3 week washout period was used before the crossover.

Titration started at 1 capsule daily, and was increased if participants had diarrhoea and reduced if the participant became constipated. Loperamide 2 mg was allowed as rescue medication if participants had uncontrolled diarrhoea.

Participants had tests to exclude other causes of diarrhoea, and stopped any previously prescribed antidiarrhoeal drugs. Additionally, women who were pregnant or breastfeeding and people who had undergone abdominal surgeries (except for appendectomy or cholecystectomy) were excluded. The exclusion criterion ‘being in the opinion of the investigator unsuitable’ was not explained. A small sample of healthy volunteers (n=21) was also studied to obtain data for normal colon transit times.

The primary outcome was stool consistency, measured by the Bristol Stool Form score. Secondary outcomes included symptoms of IBS, including pain, frequency or urgency of defaecation and bloating. Outcome data values were average scores from the last 2 weeks of each treatment period.

Results

Stool form was significantly improved when people with IBS were taking ondansetron than when taking placebo (stool form difference −0.9, 95% CI −1.1 to −0.6, p<0.001). Additionally, the IBS symptom score was reduced significantly more (by 83 points) with ondansetron compared with placebo (by 37 points, 46 point between-group difference, p=0.001).

However, people with worse diarrhoea at baseline did not respond as much as those whose diarrhoea was less severe. In the lower quartile of diarrhoea severity (average stool form 4.9), ondansetron was associated with a difference in stool form of −1.0 (95% CI −1.3 to −0.7, p<0.001). In the upper quartile of diarrhoea severity (average stool form 5.9), ondansetron was associated with a difference in stool from of −0.7 (95% CI −1.0 to −0.4, p<0.001).

Gut transit time was 46 hours in healthy volunteers but only 16 hours when people with IBS were taking placebo. Ondansetron increased gut transit time by 10 hours (95% CI 6 to 14, p<0.001).

Constipation occurred in 9% of people taking ondansetron and 2% of people taking placebo. Reducing the dose of ondansetron resolved all cases of constipation. Other side effects seen in 1 or 2 people in each group included headache, rectal bleeding, backache and abdominal pain.

Strengths and limitations

Impact on guideline

This study suggests that ondansetron may be useful for diarrhoea-predominant IBS. However, topic experts thought that the available data were not sufficient to update the guideline at this time. Another study of ondansetron in diarrhoea-predominant IBS was recommended for funding from the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research in June 2016. This new study may strengthen the case for using ondansetron in diarrhoea-predominant IBS.