What are the treatment options for functional dyspepsia?

Treatment of Functional Dyspepsia

First-Line Treatment: Test and Treat H. pylori

All patients with functional dyspepsia must undergo non-invasive H. pylori testing (breath test or stool antigen) and receive eradication therapy if positive, regardless of symptom subtype. 1, 2, 3

• H. pylori eradication provides modest but meaningful symptom improvement and is the initial intervention before any other pharmacotherapy 1
• This approach is prioritized by the British Society of Gastroenterology, American Gastroenterological Association, and European Society for Gastrointestinal Motility with strong recommendation and high evidence quality 1, 3

Symptom-Based Pharmacotherapy Algorithm

For Epigastric Pain Syndrome (EPS): Acid Suppression

Proton pump inhibitors (PPIs) are the first-line pharmacotherapy for patients with predominant epigastric pain or burning, particularly after H. pylori testing/treatment. 1, 3

• Use the lowest effective PPI dose to minimize risks of long-term complications 1
• H2 receptor antagonists are an alternative for EPS if PPIs are not tolerated 1
• PPIs carry risks including acute tubulointerstitial nephritis, Clostridium difficile-associated diarrhea, bone fractures with long-term use, drug-induced lupus, cyanocobalamin deficiency, and hypomagnesemia 4

For Postprandial Distress Syndrome (PDS): Prokinetics

Prokinetic agents are first-line for patients with predominant fullness, bloating, or early satiety. 1

• Acotiamide, itopride, mosaprid, and tegaserod have varying levels of evidence, with tegaserod having the strongest recommendation 3
• Metoclopramide is the only widely available effective prokinetic in many regions, but must be limited to short-term use (maximum 12 weeks) due to risk of tardive dyskinesia 5, 6
• The risk of tardive dyskinesia increases with duration of treatment, total cumulative dose, older age (especially women), and diabetes 5
• Metoclopramide can also cause neuroleptic malignant syndrome, acute dystonic reactions (especially in patients <30 years), parkinsonian symptoms, and depression with suicidal ideation 5
• Avoid combining prokinetics with medications that prolong QT interval 1, 2

Second-Line Treatment: Tricyclic Antidepressants

Low-dose tricyclic antidepressants (TCAs) are recommended as second-line therapy when H. pylori eradication and initial pharmacotherapy fail, particularly for EPS. 1, 2, 3

• Start with amitriptyline 10 mg once daily at bedtime, slowly titrating to 30-50 mg as tolerated 2, 3
• TCAs address visceral hypersensitivity and are effective for refractory symptoms 6, 7
• Screen patients with depression history carefully, as metoclopramide should be avoided in those with prior depression 5

Lifestyle and Dietary Modifications

Regular aerobic exercise is strongly recommended for all functional dyspepsia patients. 1, 3

Patients should avoid specific foods that trigger their symptoms, but must not adopt overly restrictive diets that risk malnutrition or disordered eating. 1, 2

• There is insufficient evidence to recommend specialized diets including low FODMAP diets 1
• Critical pitfall: Screen patients with severe FD presenting with weight loss and food restriction for avoidant restrictive food intake disorder (ARFID) and other eating disorders 1
• Refer to a dietitian early in refractory cases to prevent overly restrictive dietary patterns 1

Management of Refractory Cases

Patients with severe symptoms refractory to first and second-line treatments require multidisciplinary management including primary care physicians, dietitians, gastroenterologists, and psychologists. 1, 2

• Combination therapies may be considered, such as dual therapy with different medication classes or TCA combined with SSRI 2
• Psychotherapy is effective for patients with severe symptoms and refractoriness 8
• Establish an empathic relationship and explain that functional dyspepsia is a disorder of gut-brain interaction, not a psychological condition 1
• Critical safety warning: Avoid opioids and surgery in patients with severe or refractory functional dyspepsia to minimize iatrogenic harm 1

When to Perform Endoscopy

Urgent endoscopy is warranted in patients ≥55 years with weight loss, or those >40 years from high-risk areas for gastric cancer or with family history of gastro-oesophageal cancer. 1

• Non-urgent endoscopy should be considered in patients ≥55 years with treatment-resistant dyspepsia or dyspepsia with raised platelet count, nausea, or vomiting 1
• Full blood count should be performed in patients ≥55 years with dyspepsia 1
• Coeliac serology should be checked in patients with overlapping IBS-type symptoms 1
• Urgent abdominal CT scanning should be considered in patients ≥60 years with abdominal pain and weight loss to exclude pancreatic cancer 1
• In adults, symptomatic response to PPI therapy does not exclude gastric malignancy; consider additional diagnostic testing in those with suboptimal response or early relapse 4

Alternative and Complementary Therapies

Iberogast (STW-5) may be considered as an alternative or supplement to conventional prokinetics, especially for patients with mixed symptoms of both pain and motility disorders. 3

• This botanical preparation has positive evidence but is not explicitly mentioned in major guidelines, likely due to regional availability and prioritization of therapies with higher evidence quality 3