Irritable Bowel Syndrome
Clinical Snapshot
Irritable bowel syndrome (IBS) is a chronic, relapsing disorder of gut-brain interaction (the current terminology for what was previously called a functional gastrointestinal disorder) characterized by recurrent abdominal pain or discomfort together with altered bowel habits — constipation, diarrhea, or an unpredictable mix of both — without any structural or biochemical abnormality that fully explains the symptoms.[1]
There is no biomarker for IBS. The underlying pathophysiology is multifactorial, involving visceral hypersensitivity, altered gastrointestinal motility, low-grade mucosal immune activation, disruption of the gut microbiota, and dysregulated signalling along the brain-gut axis, often compounded by psychological comorbidity. Because no test can confirm the diagnosis, IBS is identified through a positive, symptom-based diagnostic process — the current Rome V criteria — combined with a limited, targeted set of investigations to exclude the small number of alternative diagnoses that can mimic it, rather than an open-ended process of exclusion.[2]
Symptoms fluctuate over time, and a substantial proportion of patients migrate between subtypes as their bowel habit pattern changes, so both diagnosis and treatment selection need to be revisited whenever the predominant pattern shifts rather than fixed permanently at the first visit.
Recognize the Condition
Typical presentation
Recurrent abdominal pain or discomfort, often crampy and variable in location, that is characteristically related to defecation — improved, worsened, or otherwise clearly linked to a bowel movement — together with a change in stool frequency, a change in stool form/appearance, or both. Bloating and abdominal distension are extremely common accompanying complaints, as is a sensation of incomplete evacuation and passage of mucus with stool. Symptoms typically wax and wane over weeks to months and are frequently triggered or worsened by meals, stress, or hormonal changes.
Physical examination
Usually unremarkable. Mild, diffuse abdominal tenderness on palpation may be present, but a normal examination is expected and does not argue against the diagnosis. An abdominal mass, ascites, or focal peritoneal signs is not consistent with uncomplicated IBS and should prompt urgent further assessment.
The IBS subtypes
Subtyping is based on the Bristol Stool Form Scale (a 7-point scale from hard, lumpy stool at one extreme to entirely liquid stool at the other) applied to bowel movements on days with an abnormal stool, and should be reassessed whenever a patient's bowel habit pattern changes.[1]
IBS with predominant constipation (IBS-C)
Bristol type 1-2 stool on more than one-quarter of abnormal-stool days, and Bristol type 6-7 stool on less than one-quarter of those days.
IBS with predominant diarrhea (IBS-D)
Bristol type 6-7 stool on more than one-quarter of abnormal-stool days, and Bristol type 1-2 stool on less than one-quarter of those days.
IBS with mixed bowel habits (IBS-M)
Bristol type 1-2 stool on more than one-quarter of abnormal-stool days, and Bristol type 6-7 stool on more than one-quarter of those days as well. A subset of patients labelled IBS-M actually have "pseudo-IBS-M": overflow diarrhea occurring around a background of unresolved constipation. This distinction matters because pseudo-IBS-M is treated by targeting the underlying constipation, not by adding an antidiarrheal.
IBS unclassified (IBS-U)
Meets the diagnostic criteria for IBS but the bowel habit pattern cannot be reliably categorized into the three patterns above.
Risk Factors
- Family history of IBS or another disorder of gut-brain interaction.
- Personal history of anxiety, depression, or other psychological comorbidity.
- History of an acute gastrointestinal infection — post-infectious IBS can follow bacterial, viral, or parasitic gastroenteritis.
- Early-life adverse events or significant psychosocial stress/trauma.
- Female sex.
- Overlapping disorders of gut-brain interaction or centrally mediated conditions — fibromyalgia, chronic fatigue syndrome, interstitial cystitis/bladder pain syndrome, temporomandibular disorder, chronic pelvic pain.
- Reported intolerance or sensitivity to specific dietary components, particularly fermentable carbohydrates and wheat-containing foods.
- Prior antibiotic exposure.
Red Flags & Refer
The following alarm features are not explained by uncomplicated IBS and should prompt further investigation rather than a presumptive IBS diagnosis or empiric IBS treatment.[3]
- Rectal bleeding or melena.
- Unexplained/unintentional weight loss or loss of appetite.
- Nocturnal gastrointestinal symptoms — pain or diarrhea that wakes the patient from sleep, since daytime-only symptoms are typical of IBS and night-waking symptoms are not.
- Symptom onset after age 50.
- Family history of colorectal cancer, inflammatory bowel disease, or celiac disease.
- Palpable abdominal mass or ascites on examination.
- Fever.
- Unexplained iron-deficiency anemia.
- Elevated white blood cell count or other unexplained laboratory abnormality.
- A recent, distinct change in symptoms or bowel habits in a patient with previously stable IBS.
- Severe, progressively worsening symptoms.
Any of these findings warrants further workup (typically including colonoscopy) before attributing symptoms to IBS, and referral to gastroenterology whenever management strategies for confirmed IBS are ineffective despite optimized therapy.[3]
Assessment & Diagnosis
Conditions commonly confused with IBS
Several conditions produce a similar symptom picture to IBS, particularly IBS-D and IBS-M, and should be considered before finalizing an IBS diagnosis, especially if any alarm feature is present or first-line therapy fails.
| Condition | Overlapping features with IBS | Distinguishing clue / test |
|---|---|---|
| Celiac disease | Abdominal pain, bloating, diarrhea, altered bowel habit | IgA tissue transglutaminase serology, ± duodenal biopsy; more common in IBS-D and IBS-M |
| Inflammatory bowel disease | Abdominal pain, diarrhea, urgency | Elevated fecal calprotectin/CRP, nocturnal symptoms, weight loss, blood in stool, extraintestinal findings |
| Microscopic colitis | Chronic watery diarrhea, cramping | Normal-appearing colon on colonoscopy with diagnostic changes on random biopsy; more common in older adults and with certain drug exposures |
| Bile acid malabsorption | Chronic watery diarrhea and urgency, overlaps heavily with IBS-D | SeHCAT scan or fecal bile acid testing where available, or a therapeutic trial of cholestyramine; found in a meaningful proportion of patients who otherwise meet IBS-D criteria |
| Lactose intolerance / other carbohydrate malabsorption | Bloating, gas, diarrhea after specific foods | Symptom correlation with dairy/fermentable-carbohydrate intake, hydrogen breath testing where available, or an empiric elimination trial |
| Colorectal cancer | Altered bowel habit, abdominal pain, particularly relevant with new constipation-predominant symptoms | Colonoscopy; consider especially with any alarm feature or onset after age 50 |
Diagnostic criteria — Rome V (current since June 2026)
Rome V replaced Rome IV as the current diagnostic standard and made two clinically important changes to the IBS criteria: the required symptom frequency was lowered, and "discomfort" was reinstated alongside pain as a qualifying symptom.[1]
| Rome V clinical diagnostic criteria for IBS | |
|---|---|
| Recurrent abdominal pain or discomfort, present on at least 3 days per month over the last 3 months (not required to be continuous — continuous pain suggests centrally mediated abdominal pain syndrome rather than IBS), associated with 2 or more of the following: | |
| 1 | Related to defecation |
| 2 | Associated with a change in frequency of stool |
| 3 | Associated with a change in form (appearance) of stool |
Symptom onset should be at least 6 months before diagnosis. This is a meaningful loosening of the prior Rome IV threshold, which required pain at least 1 day per week and did not recognize discomfort as a qualifying symptom on its own — a patient who did not strictly meet Rome IV criteria may now meet Rome V criteria, and real-world validation shows Rome V identifies a somewhat different population than Rome III/IV rather than simply a larger version of the same population.[4]
Treat these criteria as a framework rather than a rigid checklist: a patient who falls just short of literal criteria fulfillment but otherwise has a classic, alarm-feature-free presentation can still reasonably be managed as IBS.
History
- Bowel movement frequency and stool appearance (Bristol Stool Form Scale) to establish subtype.
- Abdominal pain characteristics — location, frequency, severity, duration, and relationship to defecation — plus associated bloating, distension, or flatulence.
- Potential symptom triggers: specific foods, personal stress, relationship or occupational stressors.
- Family history of IBS or other gastrointestinal disorders, specifically screening for the red-flag family-history conditions (colorectal cancer, IBD, celiac disease).
- Comorbid medical history, including gynecologic and urologic conditions that can mimic or overlap with IBS symptoms.
- Current medications that may be contributing to constipation or diarrhea.
- Screen specifically for reproducible food-allergy symptoms — routine testing for food allergy or food sensitivity is not indicated in patients without them.[2]
Targeted investigations
Diagnose using a positive, symptom-based strategy rather than a strategy of exhaustive exclusion — this improves both time to starting effective therapy and overall cost-effectiveness without missing clinically important alternative diagnoses, provided alarm features are absent.[2]
| Test | When to use |
|---|---|
| CBC | All patients, to assess for anemia or evidence of inflammation. |
| IgA tissue transglutaminase serology (± duodenal biopsy) | All patients with IBS-D or IBS-M symptoms, to rule out celiac disease. |
| CRP and fecal calprotectin | Patients with diarrhea symptoms and no alarm features, to rule out inflammatory bowel disease before attributing symptoms to IBS. |
| Colonoscopy | Any alarm feature present (GI bleeding, unexplained weight loss, family history of colorectal cancer, abdominal mass), or age 45 and older; not routinely required in younger patients with a typical presentation and no alarm features. |
| Random colonic biopsies during colonoscopy | Consider in patients with diarrhea symptoms to rule out microscopic colitis, particularly if colonoscopy is already being performed. |
| SeHCAT, fecal bile acid testing, or an empiric cholestyramine trial | Refractory IBS-D, given how commonly bile acid malabsorption coexists with an IBS-D symptom pattern. |
| Plain abdominal film | Selected patients, to assess for fecal loading when the severity/pattern of constipation is uncertain on history and exam. |
| Anorectal physiology testing | Symptoms suggestive of a pelvic floor disorder, or refractory constipation not responding to standard therapy. |
| Routine stool pathogen testing | Not routinely indicated in the absence of a specific exposure history or outbreak setting.[2] |
Treatment Targets
- Build a strong, ongoing patient-clinician relationship as the foundation of management.
- Reduce abdominal pain/discomfort and normalize bowel habits to a level the patient finds acceptable — IBS management targets symptom control, not a cure.
- Tailor the treatment plan to the patient's specific subtype, predominant/most bothersome symptom, and personal preferences.
- Identify and treat coexisting psychological comorbidity when present.
- Improve quality of life and support normal social and occupational functioning.
- Avoid unnecessary escalation of testing or medication once alarm features have been appropriately excluded.
Choose Initial Treatment
All subtypes — before or alongside any drug
Start every patient on nonpharmacologic measures — patient education/reassurance, regular physical activity, and dietary review — regardless of subtype; a trial of a low-FODMAP diet is reasonable in patients willing and able to follow it, ideally with dietitian support.[2]
IBS-C
1st line soluble fibre (psyllium or calcium polycarbophil), titrated gradually.
2nd line — use when soluble fibre alone is inadequate and constipation itself, rather than global symptoms, is the main problem add polyethylene glycol.
2nd line — use for inadequate global IBS-C symptom control (pain, bloating, and constipation together) despite fibre ± polyethylene glycol a guanylate cyclase-C agonist (linaclotide or plecanatide).
IBS-D
1st line soluble fibre plus loperamide taken as needed for stool consistency/urgency control — loperamide controls diarrhea but does not reliably improve overall (global) IBS-D symptoms, so it is not a complete solution on its own.[2]
2nd line — use when global IBS-D symptoms (pain plus diarrhea) remain inadequately controlled rifaximin, a 14-day course.
Alternative to rifaximin, or add-on when diarrhea/urgency remain prominent eluxadoline, only in a patient with a gallbladder and no history of pancreatitis or heavy alcohol use.
Pain-predominant symptoms, IBS-M, or inadequate response to the subtype-directed therapy above
2nd line a low-dose tricyclic antidepressant (amitriptyline first-line among the TCAs), started low and titrated to effect — this is the most consistently evidence-supported drug class for global IBS pain.[5]
Special situation antispasmodics may be used for short-term relief of pain/cramping episodes, particularly around meals or anticipated triggers; evidence for this specific use is low quality, and current ACG guidance advises against relying on this class for global symptom control.[2]
Offer gut-directed psychotherapy (cognitive behavioural therapy or gut-directed hypnotherapy) at any point in this pathway, either alongside pharmacotherapy or in patients who prefer to avoid or minimize medication.
Non-Pharmacologic Treatment
The patient-clinician relationship
A strong therapeutic relationship measurably improves outcomes in IBS and is itself part of treatment, not just a courtesy before it. Key elements: active listening to the patient's concerns, not interrupting, using empathy, setting realistic expectations about what treatment can achieve, and using non-verbal techniques such as eye contact and open body posture. A multidisciplinary approach — involving a pharmacist, dietitian, and psychologist as needed — is recommended.[3]
Lifestyle
- Encourage regular physical activity; sustained increases in activity have long-term benefit for both GI and associated psychological symptoms.
- Limit caffeine intake to 400 mg/day or less, similar to general-population guidance — evidence specific to IBS is limited.
- Counsel against binge drinking specifically (rather than light/moderate alcohol intake), which is associated with worsened GI symptoms, particularly in IBS-D.
Diet
- Low FODMAP diet: a limited trial (a restriction phase followed by structured, systematic reintroduction) improves global IBS symptoms for many patients and is recommended as a dietary option, ideally with dietitian involvement to guide reintroduction and avoid unnecessary long-term restriction and nutritional deficiency.[2]
- Fibre: soluble fibre (psyllium, calcium polycarbophil) has consistent evidence of benefit for global IBS symptoms; insoluble fibre (e.g., wheat bran) does not and should not be recommended as an IBS treatment.[2] Start fibre at a nominal dose and titrate gradually over several weeks to a total daily intake around 20-30 g, since starting at a high dose worsens bloating and gas.
- Gluten-free diet: not recommended in the absence of confirmed celiac disease — test for celiac disease before considering gluten restriction rather than restricting empirically.
- IgG-based elimination diets: not recommended — the supporting evidence is very low quality.
Gut microflora
- Probiotics: evidence is heterogeneous and of very low overall quality across strains/formulations; current ACG guidance advises against routine use for global IBS symptoms, a shift from the earlier, broader positioning of probiotics as generally recommended.[2]
- Prebiotics: evidence is limited to isolated trials (e.g., guar gum) and does not support routine recommendation.
- Fecal microbiota transplantation: not recommended for IBS outside of a research setting given the current evidence base.[2]
Psychological treatment
Gut-directed psychotherapies — cognitive behavioural therapy, gut-directed hypnotherapy, and mindfulness-based therapy — are recommended to improve global IBS symptoms and can be offered at any point in management, not only after pharmacologic options have failed.[2]
Special Populations
- IBS-C in pregnancy: adequate hydration, physical activity, and dietary fibre first; psyllium and calcium polycarbophil are first-choice pharmacologic options given minimal systemic absorption. Senna or bisacodyl may be used short-term if bulk-forming fibre is inadequate. Dicyclomine has been used safely in pregnancy, though breastfeeding data are lacking. Pinaverium, linaclotide, plecanatide, and prucalopride are not recommended in pregnancy or breastfeeding given insufficient human safety data.
- IBS-D in pregnancy: psyllium and calcium polycarbophil are safe and compatible with both pregnancy and breastfeeding. Colesevelam may be used for bile-acid-malabsorption-related diarrhea when benefit outweighs risk, with fat-soluble vitamin supplementation given reduced absorption. Loperamide has not been associated with teratogenicity but is not formally established as safe in pregnancy; small amounts transfer into breast milk and are unlikely to affect the infant. Diphenoxylate-atropine should not be used in pregnancy or breastfeeding — teratogenic in animal studies, with an active metabolite that likely transfers into breast milk. Eluxadoline and rifaximin have insufficient pregnancy/lactation safety data.
- Low-dose TCAs for pain: use only when nondrug measures and safer options are inadequate, at the lowest effective dose.
Pediatrics
IBS occurs in children and adolescents and is diagnosed using pediatric-adapted symptom criteria; management emphasizes nonpharmacologic measures and dietary review first. Psyllium and polyethylene glycol have established pediatric dosing. Linaclotide, plecanatide, eluxadoline, and rifaximin are not established for routine pediatric use in IBS — refer to pediatric gastroenterology rather than extrapolating adult dosing.
Older adults
Use caution with the anticholinergic burden of TCAs and antispasmodics (dry mouth, constipation, cognitive effects, falls risk). Avoid supratherapeutic loperamide dosing, which carries a real risk of cardiac dysrhythmia at doses above the labelled maximum. Prucalopride and eluxadoline both require reduced starting doses at age 65 and older.
Renal and hepatic impairment
Prucalopride requires dose reduction in severe renal impairment (creatinine clearance 30 mL/min or less) and severe hepatic impairment. Eluxadoline requires the lower 75 mg twice-daily starting dose in mild-to-moderate hepatic impairment and should not be used in severe hepatic impairment (Child-Pugh class C). Rifaximin needs no dose adjustment in mild-to-moderate hepatic impairment but should be used cautiously in severe (Child-Pugh class C) impairment given increased systemic absorption.
Monitoring & Follow-Up
Reassess symptom response at an interval appropriate to the agent chosen — most pharmacologic options should show a meaningful benefit within 4 weeks; discontinue and reassess the plan if there is no benefit by then, and specifically discontinue eluxadoline sooner if severe constipation persists beyond 4 days. Re-screen for newly developed alarm features at every follow-up, since a stable, long-standing IBS pattern can still be interrupted by a new, unrelated diagnosis. Monitor adherence and agent-specific adverse effects — anticholinergic burden with TCAs/antispasmodics, electrolyte status with heavy or prolonged laxative use, and gallbladder/alcohol-use status before continuing eluxadoline. Revisit IBS subtype classification whenever the bowel habit pattern changes, since this can change the appropriate drug class. Screen for psychological comorbidity on an ongoing basis, not only at diagnosis, and reinforce the value of gut-directed psychotherapy at any point that symptoms remain bothersome.[2]
Common Errors to Avoid
- Diagnosing IBS only after an extensive negative exclusion workup instead of using a positive, Rome-based diagnostic strategy in a patient without alarm features.
- Missing an alarm feature (GI bleeding, unexplained weight loss, nocturnal symptoms, onset after age 50, relevant family history) and treating presumptively as IBS.
- Treating every patient the same way rather than tailoring therapy to subtype and predominant symptom.
- Recommending insoluble fibre (e.g., wheat bran) expecting the same benefit as soluble fibre.
- Relying on continuous, scheduled loperamide as a complete IBS-D treatment — it controls stool consistency/urgency but does not reliably improve pain or global symptoms.
- Starting a tricyclic antidepressant at a full antidepressant-range dose instead of the much lower IBS-specific starting dose.
- Prescribing eluxadoline in a patient without a gallbladder, with a history of pancreatitis, or with heavy alcohol use — an absolute contraindication given pancreatitis/sphincter of Oddi risk.
- Assuming probiotics are a reliable, evidence-based fix for IBS symptoms — the evidence is heterogeneous and of very low overall quality, and current guidance recommends against routine use.
- Missing bile acid malabsorption as a contributor in refractory IBS-D.
- Failing to re-triage a patient whose previously stable, typical IBS pattern has newly changed.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Bulk-forming agents (soluble fibre)
Soluble fibre has consistent trial evidence for global IBS symptoms across subtypes; insoluble fibre (e.g., wheat bran) does not and should not be recommended.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Psyllium | Adults: Start with a nominal dose; titrate over several weeks to 15-20 g/day in divided doses, each with at least 250 mL fluid | Bloating, flatulence, mild abdominal discomfort; esophageal/intestinal obstruction if taken without adequate fluid | Titrate gradually to reduce gas/bloating. Separate other oral medications (digoxin, warfarin, carbamazepine, lithium especially) by at least 2 hours. |
| Calcium polycarbophil | Adults and children over 12 years: 2 caplets (1.25 g) PO up to 4 times daily, maximum 8 caplets (5 g)/24h, each with at least 250 mL fluid | Bloating, flatulence; esophageal/intestinal obstruction if taken without adequate fluid | Separate other oral medications by at least 3 hours. |
Osmotic laxatives
For constipation specifically, not for global IBS symptom relief; add on to fibre rather than substituting for it when pain/bloating persist alongside constipation.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Polyethylene glycol 3350 | Adults: 17 g PO once daily dissolved in 250 mL fluid | Bloating, cramping, nausea, diarrhea with excess dose | May take 2-4 days for effect. Do not use for more than 1 week without medical guidance. |
Guanylate cyclase-C agonists
Recommended for global IBS-C symptoms including pain, not just constipation itself. Lubiprostone, a related chloride channel activator with similar evidence, is not currently marketed in Canada.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Linaclotide | Adults: 290 mcg PO once daily on an empty stomach, 30 minutes before the first meal of the day | Diarrhea (can be dose-limiting), abdominal pain, flatulence, viral-gastroenteritis-like symptoms | Not significantly systemically absorbed; no clinically significant systemic drug interactions expected. Do not chew the beads; may be opened into applesauce or water for swallowing difficulty. Avoid a high-fat breakfast, which can cause looser stools.[2] |
| Plecanatide | Adults: 3 mg PO once daily, with or without food | Diarrhea | Similar efficacy and tolerability to linaclotide in comparative evidence. May be crushed into applesauce or water, or given via feeding tube, if swallowing whole is not possible.[2] |
Serotonin 5-HT4 receptor agonist (prokinetic)
Prucalopride is approved for chronic idiopathic constipation and may be considered specifically for the constipation component of IBS-C when other measures are inadequate; evidence for improving global IBS-C symptoms is weaker than for guanylate cyclase-C agonists. Tegaserod, an older 5-HT4 agonist once used for IBS-C, is not currently marketed in Canada.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Prucalopride | Adults: 2 mg PO once daily | Nausea, diarrhea, abdominal pain, headache | Reduce to 1 mg once daily if age 65 or older, creatinine clearance 30 mL/min or less, or severe hepatic impairment; otherwise no adjustment needed. Discontinue if no benefit within 4 weeks. Consider a short-term rescue laxative if there is no bowel movement by day 3-4. |
Antispasmodics
Evidence for global symptom control is low quality; current ACG guidance recommends against routine use for this purpose, while short-term use for pain/cramping episodes around meals or anticipated triggers remains a reasonable option.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Dicyclomine | Adults: 10-20 mg PO 3-4 times daily, individualized to response and tolerance | Dizziness, dry mouth, blurred vision, drowsiness, nervousness, weakness | Expect relief of pain within about 1 hour if effective; discontinue if not effective within 2 weeks. Avoid combining with other anticholinergic drugs.[2] |
| Pinaverium | Adults: 50 mg PO 3 times daily, may increase to a maximum of 100 mg 3 times daily | Esophageal irritation | Take with a full glass of water and food; do not chew, crush, or take just before lying down. |
| Hyoscine butylbromide | Adults: 10-20 mg PO 1-2 times daily, up to a maximum of 60 mg/24h | Anticholinergic effects — dry mouth, blurred vision, urinary retention, tachycardia | For short-term relief of GI smooth-muscle spasm/pain. |
| Trimebutine | Adults: Up to 600 mg/day PO in divided doses, taken before meals — e.g., 200 mg 3 times daily | Mild anticholinergic-type effects; rare allergic reaction | Has combined antispasmodic and prokinetic activity; taken before meals. |
Antidiarrheals
First-line symptomatic control of stool consistency and urgency in IBS-D; do not rely on this class alone for global symptom control.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Loperamide | Adults: 4 mg PO after the first loose stool, then 2 mg after each subsequent loose stool, maximum 16 mg/24h | Constipation; cardiac dysrhythmia with supratherapeutic doses | Use PRN or prophylactically before anticipated triggers rather than on a fixed schedule. Do not exceed the labelled maximum daily dose, given the cardiac risk of higher doses. |
| Diphenoxylate/atropine | Adults: 5 mg PO initially, then 2.5 mg after each loose stool, maximum 20 mg/24h | Sedation, nausea, abdominal cramps, anticholinergic effects from the atropine component, dependence potential at high dose | Older adults are more susceptible to the anticholinergic effects of the atropine component. Avoid in pregnancy and breastfeeding. |
Gut-selective antibiotic
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Rifaximin | Adults: 550 mg PO 3 times daily for 14 days Retreatment: May be safely and effectively retreated up to 2 additional times with a further 14-day course if symptoms recur after an initial response | Diarrhea (paradoxical), nausea | Minimal systemic absorption; acts locally in the gut. Cyclosporine increases rifaximin levels via P-glycoprotein inhibition. May reduce the effectiveness of sodium-picosulfate-containing bowel preparations — use an alternate product. May reduce warfarin effectiveness; monitor INR. Use with caution in severe (Child-Pugh class C) hepatic impairment given increased systemic absorption.[2] |
Mixed opioid agonist/antagonist
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Eluxadoline | Adults under 65, standard dose: 100 mg PO twice daily with food Adults 65 and older, or dose-intolerant: 75 mg PO twice daily with food | Constipation (can be severe — discontinue if lasting more than 4 days), nausea, abdominal pain, sphincter of Oddi spasm, pancreatitis | Contraindicated without a gallbladder, with biliary duct obstruction, severe hepatic impairment, a history of pancreatitis, alcoholism, or heavy alcohol use. Avoid combining with opioids, other anticholinergics, or alcohol. |
Bile acid sequestrants
Off-label for IBS-D with suspected bile acid malabsorption; a therapeutic trial can support the diagnosis even without confirmatory testing.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Cholestyramine resin | Adults: 4 g PO 1-6 times daily, adjusted to effect | Bloating, constipation, GI upset | Binds many other oral drugs — separate other oral medications by at least 1 hour before or 4-6 hours after. Always mix with water or moist food; never take dry. |
| Colesevelam | Adults: 3 tablets PO twice daily with meals, or 6 tablets once daily with a meal, maximum 7 tablets/day | Constipation, dyspepsia | Better tolerated and binds fewer concurrent drugs than cholestyramine resin. Separate an interacting oral drug by at least 4 hours when an interaction cannot be excluded. Preferred bile acid sequestrant in pregnancy when indicated, with fat-soluble vitamin supplementation. |
Serotonin 5-HT3 receptor antagonist
Off-label, special-situation use for refractory IBS-D diarrhea/urgency not adequately controlled by first- and second-line options; not included in the 2021 ACG graded recommendations, so reserve for specialist-directed use. Alosetron, a 5-HT3 antagonist approved in the United States for severe IBS-D in women who failed conventional therapy, is not marketed in Canada.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Ondansetron | Adults, off-label starting dose: 4 mg PO once daily, titrated upward as needed to a typical effective range of 4-8 mg/day | Constipation, headache; QT prolongation at higher doses | No Health Canada indication for IBS. Start low and titrate upward every 1-2 weeks based on stool consistency/urgency response, stopping the increase once symptoms are controlled or constipation develops. Avoid combining with other QT-prolonging drugs. |
Tricyclic antidepressants (low-dose, pain modulation)
Used at doses well below the antidepressant range. The anticholinergic effect can specifically benefit IBS-D by slowing transit; use cautiously if constipation-predominant.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Amitriptyline | Adults: 10 mg PO at bedtime, titrated over 3 weeks to a maximum of 30 mg at bedtime as tolerated | Drowsiness, dry mouth, constipation, headache; QT effects at higher doses | Start low and titrate gradually; taper when discontinuing rather than stopping abruptly.[5] |
| Desipramine | Adults: 25-50 mg PO at bedtime | Drowsiness, dry mouth, headache | Alternative TCA if amitriptyline is not tolerated; anticholinergic profile may favour IBS-D. Avoid combining with other QT-prolonging drugs. |
| Imipramine | Adults: 25-50 mg PO at bedtime | Drowsiness, dry mouth, headache | Alternative TCA if amitriptyline is not tolerated. Avoid combining with other QT-prolonging drugs. |
Selective serotonin reuptake inhibitors
Used at standard antidepressant doses (unlike TCAs, which are used at much lower doses for IBS). The 2021 ACG guideline found that the benefit of antidepressant therapy on abdominal pain was attributable to TCAs, not SSRIs — reserve SSRIs for patients with comorbid depression/anxiety or TCA intolerance rather than as a primary pain-modulating choice.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Citalopram | Adults: 20 mg PO once daily | Nausea, dry mouth, sleep disturbance, sexual dysfunction, GI bleeding risk, dose-dependent QTc prolongation | Start low and titrate based on response. Avoid combining with other QT-prolonging drugs.[2] |
| Fluoxetine | Adults: 20 mg PO once daily | Nausea, insomnia, sexual dysfunction, GI bleeding risk | Start low and titrate based on response. |
| Paroxetine | Adults: 20 mg PO once daily | Nausea, drowsiness, fatigue, sexual dysfunction, GI bleeding risk | Start low and titrate based on response. |
| Escitalopram | Adults: 10 mg PO once daily | Nausea, sexual dysfunction, GI bleeding risk | Start low and titrate based on response. |
Stimulant laxatives (short-term use, including in pregnancy)
Reserve for short-term use (generally under 1 week) when bulk-forming fibre alone is inadequate for IBS-C constipation.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Senna | Adults and children 12 years and older: 1-2 tablets PO once daily, usually at bedtime, up to a maximum of 4 tablets twice daily | Abdominal cramping, diarrhea with higher doses | Onset of action is usually 6-12 hours; often taken at bedtime. Do not use for more than 1 week without medical advice. |
| Bisacodyl | Adults: 5-10 mg PO once daily, or one 10 mg suppository rectally once daily | Abdominal cramps, diarrhea | Do not use for more than 1 week without medical advice. |
References
- Disorders of Gut-Brain Interaction and the Rome V Process — Gastroenterology (Drossman DA, Chang L, Tack J). Gastroenterology 2026;170(6):1083-1098
- ACG Clinical Guideline: Management of Irritable Bowel Syndrome — American Journal of Gastroenterology, American College of Gastroenterology (Lacy BE, Pimentel M, Brenner DM, et al.). Am J Gastroenterol 2021;116(1):17-44
- Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS) — Journal of the Canadian Association of Gastroenterology (Moayyedi P, Andrews CN, MacQueen G, et al.). J Can Assoc Gastroenterol 2019;2(1):6-29
- The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study — The Lancet Gastroenterology & Hepatology (Goodoory VC, Ford AC, et al.). Lancet Gastroenterol Hepatol 2026;11(9):812-820
- Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial — The Lancet (Ford AC, Wright-Hughes A, Alderson SL, et al.). Lancet 2023;402(10414):1773-1785
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.