Approach

The main goal of treatment is to decrease the severity of symptoms and improve quality of life.

Pharmacological therapy is frequently used, in addition to lifestyle and dietary modifications. Placebo effect may be robust; one meta-analysis found that more than one quarter of patients with IBS experienced significant improvement in global symptoms with placebo treatment alone.[52]

Lifestyle and dietary modifications

It is important to establish an effective therapeutic relationship with each patient, and to provide education and reassurance.

Initial treatments should be conservative, including discussion of lifestyle changes that may lessen stress. Possible precipitating substances, such as caffeine, lactose, or fructose, may need to be eliminated from the diet. Symptom monitoring with a diary can be helpful to identify precipitating substances and factors. UK guidelines recommend that all patients should be advised of the potential benefits of regular exercise, citing evidence from randomised controlled trials (RCTs) that this can be beneficial, particularly for constipation.[53] However, US guidelines do not recommend exercise as a treatment.[39] One Cochrane review reported that physical activity may improve symptoms, but not quality of life or abdominal pain, in people with IBS, although the certainty of evidence was very low.[54]

Dietary advice should be given to all patients who can associate triggering or worsening of their IBS symptoms with eating food (this encompasses over 80% of patients with IBS) and who are motivated to make the necessary changes.[55] Referral to a registered dietitian nutritionist (RDN) should be made for patients who are willing to engage and patients who are not able to implement recommended dietary changes on their own.[55]

Low FODMAP diet

A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet is recommended.[34][39][53] The low FODMAP diet is the most evidence-based diet for treating IBS.

FODMAPs are poorly absorbed short-chain carbohydrates that are prone to cause symptoms in patients with IBS. The low FODMAP diet induces favourable changes in the intestinal microbiota and significantly diminishes histamine, which may play a provocative role in some patients.[56][57]

A diet low in FODMAPs has been shown to improve multiple symptoms, including diarrhoea, flatus, bloating, and pain.[58][59][60][61][62]​​ However, RCTs have typically been of short duration and at risk of bias.[63][64] One meta-analysis showed significant superiority of a low FODMAP diet over British Dietetic Association dietary advice in reducing abdominal pain, bloating, and distension.[65] One European randomised trial found that in patients with IBS in primary care, a smartphone FODMAP-lowering diet application was superior to an antispasmodic agent in improving IBS symptoms. The authors concluded that a low FODMAP diet should be considered the first-line treatment for IBS in primary care.[66] However, it is uncertain which patients respond to specific FODMAP restrictions and adherence can be an issue.

Clinicians should consider an individualised approach to the low FODMAP diet, such as dietary restriction relevant to the patients' ethnicity, symptom profile, and usual dietary intake.[67]

Before recommending a restrictive diet of this nature, it is important to exclude disordered eating behaviours and eating disorders through careful history taking, as these are common in patients with gastrointestinal disorders.[55] Screening for malnutrition using a validated tool should also be considered. If the results indicate malnutrition, the patient is not suitable for dietary restrictions and should be referred to an RDN for a comprehensive nutritional assessment.[55]

A low FODMAP diet consists of three phases: restriction of FODMAP foods (lasting no more than 4-6 weeks); reintroduction of FODMAP foods; and personalisation of ongoing diet based on the outcome of reintroduction. These diet interventions should be attempted for a predetermined time period, and ideally supervised by a registered dietitian.[55] Studies have demonstrated that 4-6 weeks of a low FODMAP diet is sufficient to determine whether a patient is going to respond.[55]

It remains unclear whether a gluten-free diet is of similar benefit to patients with IBS, with mixed results from RCTs.[55][68][69] Currently, a gluten-free diet is not recommended for the treatment of IBS.[53]

Probiotics

Probiotics can help reduce abdominal bloating and flatulence, alleviate pain, and improve quality of life in patients with IBS.[70]​ Response to probiotics varies between studies and individuals.[71][72]​ They are not routinely recommended due to the heterogeneity in trials regarding outcome, design, magnitude of benefit, and uncertainty regarding the most effective strain.[39][73]

Systematic review and meta-analyses indicate that composite probiotics containing Bifidobacterium infantis may be more effective than single strain probiotic therapy.[71][74]

If a patient chooses to try probiotics, one UK guideline recommends taking them for up to 12 weeks at the dose recommended by the manufacturer, and discontinuing treatment if there is no improvement in symptoms.[55]

Constipation-predominant IBS (IBS-C)

Soluble fibre

If the patient has constipation or alternating constipation and diarrhoea, then soluble fibre (found in ispaghula, oat bran, barley, and beans) is often recommended. People with IBS should avoid insoluble fibre.[34][39]​​​[53][55]​​​​ One UK guideline advises starting soluble fibre at a low dose (3-4 g/day) and building up gradually to avoid bloating.[53]

Effectiveness has not been consistently demonstrated, but the lack of significant adverse effects makes soluble fibre a reasonable first-line therapy for patients with IBS with symptoms.[7][39][75][76][77]​​​

Osmotic laxatives

The American Gastroenterological Association (AGA) suggests that polyethylene glycol (PEG) may be used for specific symptom relief, or as adjunctive therapy for the treatment of IBS with constipation (IBS-C).[78] American College of Gastroenterology (ACG) guidelines contradict this, however, citing a lack of evidence that PEG alleviates abdominal pain, and thus global symptoms, in patients with IBS-C.[39] They therefore recommend against the use of PEG alone for the treatment of global IBS-C symptoms, although they recognise that clinicians may use PEG as first-line treatment of constipation in IBS, given its low cost and availability.[39]

Secretagogues

Lubiprostone, linaclotide, plecanatide, or tenapanor are recommended for patients with persistent constipation despite treatment with initial laxatives.[39]​​[53][78]​​​​ One systematic review and network meta-analysis examining the relative efficacy of these secretagogues across 15 RCTs found that they were all superior to placebo.[79] Linaclotide was the most efficacious agent for relieving constipation; plecanatide had the best safety profile.[79] Analyses utilised data extracted at a 12-week timepoint; longer-term effects are unknown.

Linaclotide and plecanatide are minimally absorbed 14-amino acid peptides that bind and activate the guanylate cyclase C receptor on the luminal surface of the enterocyte. This results in increased levels of cyclic guanosine monophosphate (cGMP), a second messenger that increases secretion of intestinal fluid.[80] Plecanatide and linaclotide are comparably effective, safe, and well tolerated.[39][81]​ Diarrhoea is a common side effect of both medications.[53]

Treatment with lubiprostone, a chloride-channel 2 (CIC2) activator, is an alternative in patients with constipation-predominant IBS who do not tolerate laxatives or stool softeners, or in whom these are ineffective.[39][82][83]​ Lubiprostone is approved by the US Food and Drug Administration (FDA) for the treatment of IBS with constipation only in women aged ≥18 years. Diarrhoea is a less common adverse effect with lubiprostone than with other secretagogues; however, patients should be warned that nausea is a frequent side effect.[53]

Tenapanor, an inhibitor of the sodium-proton exchanger NHE3, is another alternative. It is effective for constipation and other global symptoms of IBS like bloating. As with linaclotide and plecanatide, diarrhoea is a side effect.[53]

Tegaserod

Tegaserod, a serotonin-4 (5HT-4) receptor partial agonist, was previously recommended in some countries for the treatment of IBS with constipation in women aged under 65 years with ≤1 cardiovascular risk factor who did not adequately respond to secretagogues.[39] Tegaserod was originally withdrawn from the US market in 2007 following concerns about an increased risk of cardiovascular events. In 2019, based on a safety review, the FDA approved the reintroduction of tegaserod in the US. The drug has never been approved by the European Medicines Agency.[84][85]​​ According to a 2022 announcement, tegaserod has been withdrawn once again from the US market in June 2022; the withdrawal is reported to be because of commercial reasons and not because of product safety and efficacy or imposed recall.[86] The manufacturer has stated that the drug will be available in the US market until the depletion of existing supplies. 

Diarrhoea-predominant IBS

Antidiarrhoeals

Loperamide and opioid agonists/antagonists (e.g., eluxadoline) are variously recommended for patients with diarrhoea-predominant IBS.[34][39][87]

Loperamide is a synthetic peripheral opioid agonist. It inhibits peristalsis and antisecretory activity and prolongs intestinal transit time with limited penetrance of the blood-brain barrier.[87]

The ACG and AGA both note that loperamide improves diarrhoea but not global IBS symptoms.[39][87]

Eluxadoline is a minimally absorbed mixed opioid receptor agonist and antagonist that was developed to reduce abdominal pain and diarrhoea in patients who have IBS with predominant diarrhoea (IBS-D), without constipating side effects.[88] In studies it has demonstrated significant improvements in stool consistency and urgency, but less effect on abdominal pain. It may therefore be more useful in patients with IBS-D with predominant and troublesome diarrhoea than in those with predominant or more severe abdominal pain.[87] Eluxadoline is contraindicated in patients without a gallbladder or in patients who drink more than 3 alcoholic beverages per day because of increased risk of pancreatitis resulting in hospitalisation or death.[89]

Colestyramine

Colestyramine may be more effective than loperamide in patients who have had a cholecystectomy. If bile acid-related diarrhoea is suspected, a trial of colestyramine may be warranted, either empirically or following testing if available.[40]

Alosetron

Alosetron is a 5-HT3 antagonist; these have been shown to significantly improve symptoms in patients with IBS-D.[90][91]

Availability of alosetron may be restricted due to safety concerns. It was originally approved by the FDA in 2000 for the treatment of IBS-D in women; however, it was voluntarily withdrawn due to serious adverse events, particularly ischaemic colitis and serious complications of constipation.[87][91][92]​​ It was reintroduced in 2002, but with use restricted to the treatment of severe IBS-D in women under a risk management programme. Though safety risks with alosetron still exist, the FDA has discontinued the risk management programme. Counselling patients on the signs and symptoms of serious complications of constipation and ischaemic colitis is recommended. Immediate discontinuation of treatment is recommended in patients with signs or symptoms of ischaemic colitis.

Alosetron is only recommended for women with severe, diarrhoea-predominant IBS who have had symptoms for 6 months or longer, do not have physical or biochemical abnormalities of the gastrointestinal tract, and have not responded adequately to conventional treatment.[39][87]​​ Severe symptoms are defined as 1 or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or faecal incontinence, and/or disability or restriction of daily activities due to IBS.[87]

Rifaximin

Rifaximin, a minimally absorbed broad-spectrum oral antibiotic, has been shown to reduce global symptoms, bloating, abdominal pain, and loose watery stools in patients with IBS without constipation.​[72][87]​​[93][94][95] Rifaximin may be used as an initial or recurrent treatment.[87] It has been approved by the FDA as a 14-day course for the treatment of diarrhoea-predominant IBS. For recurrent symptoms, up to three courses are approved.

Pain or bloating

There are many options for treatment of pain, including lifestyle and dietary modifications.[96]

Antispasmodics

Antispasmodics may be considered for patients experiencing pain or bloating.[34][87] They act by relaxing smooth muscle, thereby reducing gut motility. One Cochrane review found that patients taking antispasmodics experienced significantly greater improvement in both abdominal pain and global IBS symptoms.[76] The effect of individual antispasmodics was difficult to interpret, however, because of the inclusion of 12 different drugs and the small number of studies evaluated for each drug. There was also considerable variation between the studies concerning diagnostic and inclusion criteria, dosing schedule, and study end points.[87]

Because of the lack of high-quality evidence available, ACG guidelines recommend against the use of antispasmodics currently available in the US to treat global IBS symptoms (dicyclomine and hyoscyamine). They concede that there are more robust data supporting the use of alternative antispasmodics available internationally.[39] The AGA differs in its guidance and does recommend hyoscyamine and dicyclomine.[78][87]​​​

Not all antispasmodic agents are universally available; for example, the non-anticholinergics mebeverine and alverine are not approved for use in the US. Mebeverine and alverine probably have similar efficacy to the anticholinergics in the management of IBS.

Peppermint oil has antispasmodic properties, and is recommended by both the ACG and AGA for the relief of global IBS symptoms.[39][78]​​[87]​​ It is available as drops or enteric-coated sustained-release tablets. Evidence is mixed. One meta-analysis found that peppermint oil reduced abdominal pain and overall IBS symptoms compared with placebo.[97] However, a subsequent RCT (that employed end points recommended by regulatory authorities) concluded that peppermint oil does not significantly reduce abdominal pain or improve overall symptom relief.[98]

Antidepressants

If pain persists despite antispasmodics, a tricyclic antidepressant (TCA), used as a gut-brain neuromodulator, may be beneficial.[39][78]​​​[87][99]​​​ TCAs are thought to improve visceral and central pain by acting on noradrenaline and dopaminergic receptors. They may also improve abdominal pain because of their anticholinergic effects. At higher doses they can slow gastrointestinal transit, which can be useful in patients with urgency and diarrhoea, but potentially problematic in patients with constipation. Secondary amine TCAs (e.g., desipramine and nortriptyline) may be better tolerated in patients with constipation-predominant IBS due to their lower anticholinergic effects.[78][87]​​

Notable adverse events include dry mouth and eyes, urinary retention, cardiac arrhythmias, sedation, and constipation, so careful patient selection is needed.[39][87] The beneficial effects of TCAs on IBS symptoms appear to be independent of effects on depression and may take several weeks.[87]

Selective serotonin-reuptake inhibitors (SSRIs) are not recommended in US guidelines because of a lack of high quality evidence that they significantly improve global symptoms or abdominal pain in patients with IBS.[39][87]

In one meta-analysis, subgroup analysis by antidepressant class found no significant benefit from SSRIs in patients with IBS and abdominal pain; the beneficial effect on abdominal pain appeared to be limited to TCAs.[100] AGA guidelines note that in some patients, however, SSRIs may improve the perception of overall IBS symptoms and well-being by improving gastrointestinal symptoms, mood, and extraintestinal symptoms.[87] UK guidelines differ from US guidelines, recommending that SSRIs can be used as an alternative to TCAs for treating global symptoms of IBS.[53]

Psychological therapies

Patients who do not respond to pharmacological treatment may need referral for more intensive psychological treatments and support.[34] One meta-analysis of RCTs of psychological therapies for IBS demonstrated that several types of therapy were more efficacious than control interventions. However, the most compelling evidence, based on the number of trials and long-term outcomes, was for IBS-specific cognitive behavioural therapy (CBT) and gut-directed hypnotherapy.[101] Both are recommended in US and UK guidelines; UK National Institute for Health and Care Excellence (NICE) guidelines specify a role for them when symptoms have not improved after 12 months of pharmacological treatment, whereas ACG guidelines recommend their use in conjunction with other IBS therapies for patients who are emotionally stable but exhibit cognitive-affective drivers of IBS.​[34][39]

Patients with predominantly pain-related symptoms may need referral to a pain specialist or clinic.

IBS occurring after enteric infection

There are no specific treatments for IBS occurring after enteric infection. It should be managed according to the predominant symptom, which is usually diarrhoea or a mixed stool pattern.[102]

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