Irritable bowel syndrome
Functional gastrointestinal disorder with abdominal pain and altered stool frequency or form. Diagnosed by Rome IV criteria. Therapy includes dietary approaches (low-FODMAP), psychotherapy, spasmolytics, low-dose antidepressants, and probiotics in selected patients.
ICD-10 K58.816 drugs
Also known as: IBS
Drugs used for this condition
- BAmitriptylineSecond line · Tricyclic antidepressants (TCA)In irritable bowel syndrome low-dose amitriptyline is second line: BSG 2021 recommends tricyclics for global symptoms and abdominal pain when first-line measures (diet, antispasmodics, laxatives or loperamide) have not helped, NICE CG61 advises them after laxatives, loperamide or antispasmodics have failed, at 5–10 mg at night and usually not above 30 mg, ACG 2021 gives a strong recommendation for tricyclic antidepressants for global IBS symptoms, and the European UEG/ESNM 2022 consensus on IBS with diarrhoea a conditional one. In the ATLANTIS 2023 RCT (n=463, English primary care), amitriptyline 10 mg titrated to 30 mg at night lowered symptom severity on the IBS-SSS by 27 points more than placebo over 6 months; 13% stopped it for side effects versus 9% on placebo. In Spain IBS is not in section 4.1 of the Tryptizol SmPC, so this is off-label use; IBS doses are far below antidepressant doses. Contraindicated after a recent myocardial infarction, with heart block or arrhythmia, coronary insufficiency, severe liver disease and with MAOIs. It very commonly causes dry mouth and constipation, which matters in constipation-predominant IBS; caution in urinary retention, angle-closure glaucoma, QT prolongation and epilepsy; the AGS Beers Criteria 2023 advise older adults to avoid it. In patients under 25, antidepressants raise the risk of suicidal behaviour. Fluoxetine, paroxetine and bupropion raise its levels; with tramadol the risk of seizures and serotonin syndrome increases. An adult dose of 750 mg or more can cause severe poisoning. In pregnancy only when clearly needed; 0.6–1% of the maternal dose passes into breast milk.
- BHyoscine butylbromideSecond line · Antispasmodic, quaternary ammonium belladonna alkaloidUsed as-needed for IBS pain episodes. Not first-line – inferior to mebeverine, otilonium bromide, and pinaverium bromide in effect duration.
- BLoperamideCase-by-case decision · AntipropulsivesIn IBS with diarrhea (IBS-D), as-needed loperamide per ACG 2021 reduces diarrheal episodes and improves stool consistency. It does not affect pain frequency or overall quality of life – other classes are needed (rifaximin, eluxadoline, antispasmodics). Use 2 mg 1–4 times daily as needed.
- BMebeverineCase-by-case decision · Antispasmodics (myotropic)Per BSG 2021 and Rome IV, myotropic antispasmodics are first-line pharmacotherapy for abdominal pain in irritable bowel syndrome. Mebeverine dose 200 mg twice daily 20 minutes before meals. Effect on abdominal pain is moderate (NNT 7), on overall QoL – small. ACG 2021 grades antispasmodic recommendations as 'conditional, low-quality evidence'. If no benefit after 4 weeks, reassess diagnosis and switch to peppermint oil, eluxadoline, rifaximin, or psychotropic agents.
- BOtilonium bromideFirst line · Intestinal antispasmodic, quaternary ammonium compoundFirst-line for pain-predominant irritable bowel syndrome per ACG 2021, BSG 2021, and Rome IV. The Ford 2014 meta-analysis of 23 RCTs reported relative risk for no response on antispasmodics of 0.68 (95% CI 0.57–0.81). Standard dose 40 mg 2–3 times daily, 20 minutes before meals. Course 4–8 weeks with the option to repeat.
- BPsyllium (Plantago ovata, ispaghula husk)Add-on therapy · Soluble and insoluble fibre from seed husk. AEMPS registered Plantaben and Cenat as medicinal products for chronic constipation and maintenance of normal defecation. ACG 2014 and NICE NG61 IBS 2017 list psyllium as the primary soluble fibrePsyllium is one of the few soluble fibres with evidence in irritable bowel syndrome, especially IBS-C. Moayyedi 2014 meta-analysis (14 RCTs, 906 patients) showed moderate global IBS symptom improvement with soluble fibre (psyllium, ispaghula), but not insoluble (wheat bran). NICE NG61 IBS 2017 in IBS-C and mixed forms lists soluble psyllium fibre with gradual dose increase first-line. ACG 2021 IBS guideline gives a strong recommendation for soluble fibre use (psyllium, ispaghula). Evidence base is stronger than for probiotics. In IBS-D, psyllium may worsen bloating in some patients – individual dose titration required. Effect develops over 2–4 weeks of use.
- CProbiotics (Lactobacillus spp., Bifidobacterium spp., Saccharomyces boulardii)Case-by-case decision · Probiotic microorganismsCochrane 2019 and AGA 2020 rated the evidence base for probiotics in IBS as moderate with high strain-dependence. Some meta-analyses showed reduced pain and bloating. AGA 2020 does not recommend probiotics for IBS in adults outside clinical trials due to result heterogeneity and study quality. In some IBS-D patients, Bifidobacterium infantis 35624 or combination preparations provide clinical improvement.
- CTrimebutineSecond line · GI motility regulator, peripheral opioid receptor agonistUsed in irritable bowel syndrome with mixed or variable bowel pattern. Evidence is modest: the 2011 Cochrane meta-analysis showed moderate benefit over placebo for symptom relief (RR 1.32, 95% CI 1.07–1.64), with low-quality studies. International guidelines (ACG 2021, AGA 2022) do not include it; it is used mostly in Spain, France, and Eastern Europe.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DBifidobacterium longumNot recommended · Probiotic, Bifidobacterium genus bacteria. Supplement in Russia and Spain; marketing segment of «psychobiotics» promising gut-brain axis effects. AEMPS does not register it as a medicineB. longum (especially B. longum NCC3001 in Pinto-Sanchez 2017 RCT) is offered for IBS with associated anxiety and depression. ACG 2021 IBS guideline gives a conditional recommendation against routine probiotic use in adult IBS: effect is strain-specific, evidence low-quality. ESNM/UEG 2022 IBS consensus states that individual strains may show effect but no single recommended strain. In an IBS patient, first line is diet discussion (low-FODMAP), psyllium as soluble fibre, antispasmodics for IBS-D, rifaximin for IBS-D. If B. longum was recommended for IBS without discussing diet, psyllium and red flags, consider seeking a second opinion from a gastroenterologist.
- DDiosmectiteNot recommended · Intestinal adsorbents (natural smectite)Small RCTs showed a modest effect of diosmectite in IBS-D. ACG 2021 does not mention it. AGA and BSG also exclude it from IBS standards. Use is justified only sporadically for symptomatic diarrhea relief – not for long-term therapy.
- DInulin (chicory/agave/Jerusalem artichoke prebiotic)Not recommended · Soluble fructan fibre, prebiotic. Supplement in Russia and Spain. EFSA approved health claim for chicory inulin on maintenance of normal defecation (2015). AEMPS does not register it as a medicineInulin in irritable bowel syndrome may WORSEN symptoms. Inulin belongs to fructans – a high-FODMAP carbohydrate group that reaches the colon in excess and ferments with active gas production, causing pain, bloating and flatulence. The low-FODMAP diet (Monash University), which NICE NG61 IBS 2017 and ACG 2021 IBS guideline list as a second-line option in IBS, EXCLUDES inulin-rich foods (onion, garlic, artichoke, chicory, agave). In IBS-C, soluble psyllium fibre (low-FODMAP) is preferable over inulin. If inulin was recommended for IBS-C, consider seeking a second opinion.
- DL-glutamine (free amino acid)Not recommended · Conditionally essential amino acid; the main nitrogen source for nucleotide synthesis and fuel for enterocytes and immune cells. Normally supplied by dietary protein (meat, fish, eggs, dairy, legumes) and synthesised in skeletal muscle. Supplements market it as a remedy for «leaky gut», post-workout recovery, immune support in cancer patients, and a sugar-craving reducer. Neither AEMPS nor EMA registers it for supplement indications; a specialty drug exists (Endari, L-glutamine, FDA-approved) for sickle-cell disease to reduce pain-crisis frequency – this is a specialised clinical niche, not a supplement. AESAN classifies general L-glutamine supplements as complementos alimenticios.L-glutamine is central to the «leaky gut» marketing concept actively pushed by integrative clinics and functional-medicine influencers. The concept: stress, antibiotics, and gluten «open» the gut wall, large molecules enter blood, autoimmune disease, allergy, and chronic inflammation follow, and L-glutamine «heals» epithelial tight junctions. Academic gastroenterology does not accept «leaky gut» as a clinical syndrome: AGA, BSG, and the Spanish SEPD do not include leaky gut in their guidelines. Increased small-bowel permeability is a physiological adaptation seen in many states (coeliac disease, Crohn's, exercise, NSAIDs, infectious gastroenteritis) without clear causality for systemic disease. The Zhou and Verne trial (Gut 2018) in 106 patients with post-infectious diarrhoeal IBS reported symptom improvement in 79% on L-glutamine 5 g three times daily for 8 weeks versus 6% on placebo – an impressive single-centre result not reproduced in larger RCTs. NICE CG61 for IBS recommends low-FODMAP diet, psychological support, and when needed – mebeverine, loperamide, SSRIs and antidepressants; glutamine is not in the guideline. If glutamine was bought «for leaky gut», consider seeking a second opinion – persistent GI symptoms warrant gastroenterology assessment to rule out coeliac disease, SIBO, inflammatory bowel disease, and eosinophilic oesophagitis.
- DLactobacillus rhamnosus GG (LGG)Not recommended · Probiotic, Lacticaseibacillus rhamnosus GG strain. Supplement in Russia and Spain; in the EU and US available as food supplement or medical food; AEMPS does not register it as a medicineLGG is offered for irritable bowel syndrome as part of multi-strain formulas. ACG 2021 IBS guideline gives a conditional recommendation against routine probiotic use in adult IBS: effect is heterogeneous, strain-specific, evidence low-quality. If a patient must choose between LGG and other options (soluble psyllium fibre, low-FODMAP diet, antispasmodics for IBS-D, rifaximin for IBS-D), LGG is not a priority option. NICE NG61 IBS 2017 states: if a patient decides to try a probiotic – minimum 4 weeks at the manufacturer-recommended dose, with effect assessment at end of course. If LGG was recommended for IBS without discussing diet, psyllium and red flags (weight loss, nocturnal symptoms, bloody stool), consider seeking a second opinion.
- DSaccharomyces boulardii CNCM I-745Not recommended · Yeast probiotic. AEMPS registered Enterol (Biocodex) as a medicinal product for AAD, travellers diarrhoea and adjunct therapy for C. difficileS. boulardii is offered for irritable bowel syndrome, especially IBS-D after acute gastroenteritis (post-infectious IBS). Small RCTs showed heterogeneous results. ACG 2021 IBS guideline gives a conditional recommendation against routine probiotic use in adult IBS. S. boulardii has no specific IBS indication in AEMPS registration dossier (Enterol registered only for AAD and travellers diarrhoea). If S. boulardii was recommended for IBS as monotherapy without discussing diet, low-FODMAP approach and red flags (weight loss, nocturnal symptoms, bloody stool, onset after 50), consider seeking a second opinion from a gastroenterologist.
- DSlippery elm (inner bark)Not recommended · Over-the-counter botanical supplement, the inner bark of Ulmus rubra (slippery elm, a North American tree); a mucilage demulcent with traditional use for irritation of the gastrointestinal and throat mucosaIn irritable bowel syndrome, slippery elm was studied in a single pilot trial. Hawrelak (J Altern Complement Med 2010) in 21 patients with IBS-C compared a herbal blend with slippery elm against no placebo control: a moderate symptom improvement was reported. This is not the level of a large blinded RCT. NICE CG61 and ACG IBS 2021 for IBS-C recommend psyllium (soluble fiber), linaclotide or plecanatide; for IBS-D – loperamide, rifaximin, eluxadoline; for mixed IBS – individualized selection. Slippery elm is not mentioned in the guidelines. There is no Cochrane review on slippery elm in IBS. AEMPS and AESAN classify the product as a complemento alimenticio without therapeutic indication. If slippery elm was bought «for IBS», discuss with a gastroenterologist – at the current evidence level the first line in IBS is drugs with proven efficacy and a low-FODMAP diet, and demulcents do not belong in this scheme.
- FDydrogesteroneNot recommended · Progestogens — pregnadiene derivativesDydrogesterone has variable evidence for dysmenorrhea and endometriosis. For pain unrelated to menstrual cycle or endometriosis, dydrogesterone is not indicated. Common Russian prescriptions for Duphaston for «hormonal imbalance», «cycle disturbance» without workup, or «luteal-phase progesterone deficiency on blood levels» lack international evidence and often mask missed differential diagnoses.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit