What is the best treatment approach for a patient with Irritable Bowel Syndrome (IBS) with diarrhea?

Treatment of IBS with Diarrhea

Start with loperamide 4-12 mg daily for diarrhea control, combined with soluble fiber (ispaghula 3-4 g/day, gradually increased) and lifestyle modifications as first-line therapy. 1

Initial Management: Diagnosis and Patient Education

• Make a positive diagnosis based on symptoms (abdominal pain with altered bowel habit for ≥6 months) without extensive testing in patients under 45 years without alarm features such as unintentional weight loss, blood in stool, fever, anemia, or family history of colon cancer or inflammatory bowel disease. 2, 1

• Obtain basic screening tests: full blood count, C-reactive protein or ESR, coeliac serology, and faecal calprotectin (in patients <45 years with diarrhea) to exclude inflammatory bowel disease. 2

• Explain the diagnosis clearly using simple analogies patients can understand—describe IBS as a "sensitive gut" with brain-gut interactions, similar to how anxiety before an exam can cause diarrhea. 2 This reduces anxiety about unexplained symptoms and prevents unnecessary referrals or potentially hazardous treatments. 2

• Consider bile acid malabsorption in patients with atypical features such as nocturnal diarrhea or prior cholecystectomy, and test with 23-seleno-25-homotaurocholic acid scanning or serum 7α-hydroxy-4-cholesten-3-one. 2, 1

First-Line Treatment: Lifestyle and Dietary Modifications

Lifestyle Changes

• Prescribe regular physical activity to all IBS-D patients, as exercise provides significant benefits for symptom management. 2, 3

• Recommend keeping a two-week symptom diary to identify dietary triggers, stressors, and patterns that exacerbate symptoms. 2

Dietary Interventions

• Identify and reduce excessive intake of lactose (>280 ml milk/day), fructose, sorbitol, caffeine, and alcohol, as these commonly trigger diarrhea. 1, 3

• Reduce fiber intake in IBS-D patients, as increased fiber worsens diarrhea symptoms. 1 Specifically, avoid insoluble fiber (wheat bran) as it exacerbates symptoms. 2

• Start soluble fiber (ispaghula/psyllium) at 3-4 g/day and increase gradually to avoid bloating, as it is effective for global symptoms and abdominal pain. 2, 1

• Consider a supervised low-FODMAP diet as second-line dietary therapy if symptoms persist, but only under supervision of a trained dietitian with planned reintroduction of foods according to tolerance. 2, 1, 3 This three-phase approach (restriction, reintroduction, personalization) is particularly effective but requires professional guidance to avoid nutritional deficits. 4

• Do not recommend gluten-free diet unless celiac disease is confirmed. 2, 1

• Do not use IgG-based food elimination diets as they are not recommended. 2, 1

Pharmacological Treatment for Diarrhea

First-Line Antidiarrheal Agent

• Prescribe loperamide 4-12 mg daily (either regularly or prophylactically before going out) to effectively reduce stool frequency, urgency, and fecal soiling. 2, 1, 3, 4 Loperamide is the most established first-line agent for diarrhea control in IBS-D. 1

• Titrate loperamide dose carefully as abdominal pain, bloating, nausea, and constipation are common and may limit tolerability. 3

Alternative Antidiarrheal Options

• Consider cholestyramine for patients with prior cholecystectomy or suspected bile acid malabsorption, though it is less well tolerated than loperamide. 2, 1

• Codeine 30-60 mg, 1-3 times daily can be tried but central nervous system effects often limit use. 4

Pharmacological Treatment for Abdominal Pain

• Use antispasmodic agents with anticholinergic properties (such as dicyclomine) as first-line therapy for abdominal pain, particularly when symptoms are meal-related. 2, 1, 3, 4

• Consider peppermint oil as an alternative antispasmodic, though evidence is more limited. 3, 4

Second-Line Pharmacological Treatments

Tricyclic Antidepressants (TCAs)

• Prescribe tricyclic antidepressants (TCAs) for moderate to severe symptoms or when first-line treatments fail, as they are the most effective pharmacological treatment for global symptoms and abdominal pain in IBS-D. 2, 1, 3, 4

• Start amitriptyline at 10 mg once nightly and titrate slowly (by 10 mg/week) according to response and tolerability, up to 30-50 mg once daily. 1, 3

• Continue TCAs for at least 6 months if the patient reports symptomatic improvement. 1, 4

• TCAs have neuromodulatory and analgesic properties independent of their psychotropic effect and alter GI physiology (visceral sensitivity, motility, and secretion) at lower doses than needed for depression. 2

SSRIs as Alternative

• Consider SSRIs (fluoxetine, paroxetine, sertraline) as an alternative when TCAs are not tolerated, particularly for patients with comorbid anxiety-related disorders, as they have low side effect profiles and better safety than TCAs. 2, 1

• If there is a concurrent mood disorder, use an SSRI instead of low-dose TCAs, because low-dose TCAs are unlikely to address psychological symptoms. 4

Probiotics

• Consider a 12-week trial of probiotics for global symptoms and bloating, and discontinue if there is no improvement. 2, 4 However, it is not possible to recommend a specific species or strain. 2

Advanced Pharmacological Options (FDA-Approved for IBS-D)

Rifaximin

• Rifaximin is FDA-approved for IBS-D and has been shown to improve abdominal pain and stool consistency with the most favorable safety profile among approved agents. 5, 6, 7

Eluxadoline

• Eluxadoline is FDA-approved for IBS-D and improves abdominal pain and stool consistency. 5, 7, 8 However, it is contraindicated in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment. 3, 5

Alosetron

• Alosetron is approved only for women with severe IBS-D in whom conventional treatment has failed, due to safety concerns including ischemic colitis. 2, 7, 9

Psychological Therapies for Refractory Cases

• Refer for IBS-specific cognitive behavioral therapy (CBT) or gut-directed hypnotherapy when symptoms persist despite first-line treatments. 1, 3

• Strongly recommend psychological therapies when symptoms are refractory to drug treatment for 12 months. 1, 3, 4

• Cognitive-behavioral treatment, dynamic psychotherapy, hypnosis, and stress management/relaxation are effective in reducing abdominal pain and diarrhea (but not constipation), and also reduce anxiety and other psychological symptoms. 2

• Greater benefit may be expected in patients who relate symptom exacerbations to stressors, have associated anxiety or depression, or have symptoms of relatively short duration with waxing and waning rather than chronic pain. 2

• These brain-gut behavior therapies are specifically designed for IBS and differ from psychological therapies that target depression and anxiety alone. 3, 4

Treatment Monitoring and Adjustment

• Review treatment efficacy after 3 months and discontinue ineffective medications. 3, 4

• Recognize that symptoms may relapse and remit over time, requiring periodic adjustment of treatment strategy. 3, 4

Referral Criteria

• Refer to gastroenterology when there is diagnostic doubt, severe or refractory symptoms, or patient request. 2, 1

• Refer to a gastroenterology dietitian if the patient consumes considerable intake of foods that trigger IBS symptoms, shows dietary deficits or nutritional deficiency, shows recent unintended weight loss, or requests dietary modification advice. 3

• Refer to a gastropsychologist if IBS symptoms or their impact are moderate to severe, the patient accepts that symptoms are related to gut-brain dysregulation, and has time to devote to learning new coping strategies. 3, 4

Important Caveats

• Avoid anxiolytics as they have weak treatment effects, potential for physical dependence, and interaction with other drugs and alcohol. 2

• Do not perform colonoscopy in IBS unless there are alarm symptoms or signs, or atypical features suggesting microscopic colitis (female sex, age ≥50 years, coexistent autoimmune disease, nocturnal or severe watery diarrhea, duration <12 months, weight loss, or use of NSAIDs/PPIs). 2

• The placebo response in IBS trials averages 47%, approximately three times larger than the additional drug effect (16%), which emphasizes the importance of the therapeutic relationship and patient education. 2