From nausea pills to hypnosis, the latest ways to beat the misery of IBS

• Irritable bowel syndrome affects the wiring system between the brain and gut 

It’s one of the most common reasons for a visit to the GP and affects millions of Britons. But people with irritable bowel syndrome (IBS) often struggle to find effective treatment for the pain, cramps, bloating and urgency, leaving many housebound and in pain or having to plan their daily lives like a military operation.

Now a study published in The Lancet has shown that a cheap (25p a day) antidepressant may alleviate symptoms in some. The UK trial found that those who took a low-dose amitriptyline pill – 10mg to 30mg – were nearly twice as likely as a placebo group to report an improvement.

IBS affects the wiring system between the brain and gut, which controls how food moves through it.

There are different types of IBS. The most common is IBS-D, characterised by diarrhoea and abdominal discomfort; IBS-C, where constipation and abdominal discomfort are the main problems; IBS-mixed, where the sufferer has alternating loose stools and constipation with abdominal discomfort; and IBS-U, where symptoms vary.

So how could an antidepressant help? It comes down to its effect on serotonin receptors in the gut, explains Alexander Ford, a professor of gastroenterology at Leeds University and co-chief investigator in the Lancet trial.

Serotonin is a chemical that carries messages between cells in the brain and elsewhere in the body. Ninety per cent of the body’s serotonin is in the gut, where it affects motility.

By working on the serotonin receptors, amitriptyline alters how messages are sent and received, changing bowel activity.

‘It also works on noradrenaline [another chemical messenger] receptors in the gut, which may be how it affects pain signalling,’ Professor Ford told Good Health.

The trial found amitriptyline reduced stomach pain significantly.

The use of amitriptyline for IBS is, in fact, not new. ‘NICE guidance already recommends that GPs consider using low-dose amitriptyline,’ explains Professor Ford. ‘However, as the evidence wasn’t very strong, this wasn’t widely adopted by GPs – but specialists in hospitals did.

‘So, most people with IBS will have been given dietary advice and told to take laxatives, anti-diarrhoeal drugs and/or anti-spasmodic drugs. However, most of these treatments have only a modest impact.

‘We hope it [amitriptyline] will now be used more widely,’ he says, adding that there are other, little-known licensed second-line treatments, such as linaclotide, which can be used in IBS-C.

Here we explore other IBS treatments.

Anti-nausea pill 

Ondansetron, currently used for patients who experience nausea and vomiting after chemotherapy, radiotherapy and surgery, may be beneficial in IBS-D, where diarrhoea is the main symptom.

Known as a 5HT3 receptor antagonist, the drug blocks the action of serotonin in the gut. And, like amitriptyline, it is cheap and widely available.

A 2014 study by Queen’s Medical Centre, Nottingham, published in the journal Gut, found ondansetron reduced loose stools, frequency and urgency in patients with IBS-D.

Robin Spiller, a professor of gastroenterology who ran the trial, said he had prescribed ondansetron off-label (for a condition other than that it is licensed for) for IBS patients ‘for some years and knew it could be effective in some’.

‘I had been studying patients who developed IBS after Campylobacter gastroenteritis [a tummy bug caused by the Campylobacter bacteria] and had shown they had an excess of serotonin-containing enteroendocrine cells [gut cells that produce serotonin],’ he says.

These cells also released more serotonin than normal after the patients ate.

He realised that because serotonin stimulates gut motility, a drug that blocks its action might improve diarrhoea.

‘For those who respond, odansetron can be life-changing,’ says Professor Spiller, who with Professor Ford is hoping to get funding for a trial along the lines of the amitriptyline study.

Bespoke bacteria 

For more than 20 years, researchers have been investigating how probiotics (good bacteria) and prebiotics (food that nourishes probiotics) may help with IBS.

The theory is that, in some, IBS symptoms arise from an imbalance in the microbiome – the billions of microbes in the gut.

Glenn Gibson, a professor of food microbiology at Reading University (who coined the term ‘prebiotics’), says both stimulate more beneficial microbes, ‘which helps reduce symptoms such as gas distension’, i.e. bloating.

The bacteria’s by-products (‘metabolites’) can also influence brain function, potentially helpful in IBS because anxiety or stress often lead to attacks. Lactobacillaceae bacteria, for example, make GABA (Gamma-Aminobutyric Acid), a chemical messenger that has a calming effect on the brain.

The metabolites are transported to the brain by the bloodstream, or communicate with it via the vagus nerve (which runs from the brain to the intestine).

At King’s College London, researchers Dr Saeed Shoaie and Dr David Moyes have been exploring the idea that IBS sufferers could be offered a more personalised approach to improving the make-up of their gut bacteria. In a 2022 paper, published in the Journal of Translational Medicine, they wrote that artificial intelligence could be used to design bespoke treatments tailored to the individual’s microbiome.

This would require a database with tens of thousands of people’s microbiome details, revealing how different gut bacteria react to different foods, supplements, lifestyles, and their age and weight.

An algorithm would then predict how an individual’s microbiome would behave, and how it should be treated. So an IBS patient could go to the doctor, give a stool sample and have personal information such as their weight recorded, and then the sample would be tested and analysed in a lab to see what strains of bacteria it contained.

Mesmerising approach to gut problem 

Gut-directed hypnosis (GDH) is where patients are put into a deep state of hypnosis before, say, visualising controlling the flow of the gut as a river.

‘IBS symptoms are caused by the gut going into spasm due to being oversensitive and therefore over-reacting to events like eating or stress,’ says Peter Whorwell, a professor of medicine and gastroenterology at Wythenshawe Hospital, Manchester, and the pioneer of GDH.

‘Using hypnosis we can teach patients to reduce the sensitivity of their gut and stop it going into spasm. We usually offer 12 sessions although some patients improve after fewer.’ While NICE guidelines state that hypnotherapy can be helpful for IBS, Professor Whorwell says uptake is not as high as it could be due to scepticism among patients and the medical profession as well as a lack of suitably trained therapists.

‘And mild IBS patients don’t necessarily need hypnotherapy – firstly, because they often respond well to first-line treatment [medication and dietary advice] and secondly, because their motivation is not very strong so they will be less likely to engage in a treatment that is quite intensive and time-consuming.’

Based on this and the patient’s other data, the computer would make a prediction, explains Dr David Moyes, a senior lecturer in host-microbiome interactions.

‘It would say, OK, you’re low in this, therefore you need to increase this food. Or it might give a tailored probiotic cocktail.’

Talking therapies

Talking therapies such as cognitive behavioural therapy (CBT) may work just as well as medication for reducing IBS symptoms, according to a trial published in the journal Gut in 2019. In the study, 558 patients were given either a form of CBT tailored to IBS, or received ‘treatment as usual’ i.e. their usual IBS treatment from their doctor.

After 12 months, the CBT patients experienced an improvement on a par with the amitriptyline study, said Rona Moss-Morris, professor of psychology as applied to medicine at King’s College London and NIHR Maudsley Biomedical Research Centre, who led the study.

What the CBT also did, which the amitriptyline didn’t, ‘was reduce the depression and the anxiety, as well as the amount that IBS was affecting people’s lives’, she says. ‘Sometimes people think if you’re offering CBT then it’s not a physical health complaint, but that’s not what we’re saying.

‘It focuses on how specific thinking patterns, behaviours and emotions can perpetuate some of the symptoms of IBS.’

For example, many people with IBS develop ‘safety and avoidance behaviours’ – they may stop going out or spend time worrying where the loos are. ‘This can create a worry cycle – and we know stress escalates the IBS,’ Professor Moss-Morris explains.

‘People often also chop and change their diet, so they’ll try this, they’ll try that, which affects their routine – and actually our bodies quite like routine.

‘So while there are dietary changes that might help, this chopping and changing is not particularly helpful. We can target these behaviours in the CBT.’

Emerging evidence also shows that our emotions can alter our microbiome, she says. This, again, can be targeted by the CBT, as a small 2022 study by the University of Buffalo in the U.S. found. Stool samples of severe IBS sufferers before and after CBT showed the microbiome had changed.

‘It’s pretty remarkable,’ said Dr Jeffrey Lackner, chief of the Division of Behavioural Medicine, who carried out the research.

Professor Moss-Morris says it is not a question of choosing between medication or CBT.

‘CBT can easily be done alongside medication,’ she says. ‘We normally suggest trying medication first, as medicines like amitriptyline are relatively cheap and quite easy to take.’

Professor Moss-Morris hopes a web-based version of CBT will soon be available on the NHS.