What are the treatment modalities for dyspepsia?

Treatment Modalities for Dyspepsia

For all patients with dyspepsia, test for Helicobacter pylori and provide eradication therapy if positive, followed by empirical acid suppression with proton pump inhibitors (PPIs) for those who remain symptomatic or test negative. 1, 2, 3

Initial Diagnostic Considerations

• Patients over 55 years with dyspepsia or those with alarm symptoms (weight loss, dysphagia, bleeding) require immediate upper gastrointestinal endoscopy before initiating empirical therapy 2, 3
• Complete blood count should be performed in patients ≥55 years, and celiac serology in those with overlapping irritable bowel syndrome symptoms 2, 3
• Establish an empathetic doctor-patient relationship and explain that functional dyspepsia is a disorder of gut-brain interaction, not a psychological condition, which reduces healthcare utilization and improves quality of life 2, 3

First-Line Pharmacological Treatment Algorithm

Step 1: H. pylori Testing and Eradication

• All patients with dyspepsia must undergo non-invasive H. pylori testing (urea breath test or stool antigen) 1, 2, 3
• If positive, provide eradication therapy as the initial intervention regardless of symptom subtype 2, 3, 4
• Confirmation of successful eradication is only necessary in patients at high risk for gastric cancer 2

Step 2: Empirical Acid Suppression (for H. pylori-negative or persistent symptoms)

• For ulcer-like dyspepsia (predominant epigastric pain): Initiate full-dose PPI therapy as first-line treatment 1, 2
• Omeprazole 20 mg once daily is effective and can confirm the acid-related nature of symptoms 1, 2
• Use the lowest effective PPI dose that controls symptoms, as there is no evidence of dose-response benefit 2
• Continue PPI therapy for 4-8 weeks initially 5

Step 3: Prokinetic Agents (for dysmotility-like symptoms)

• For dyspepsia with predominant bloating, distension, fullness, or early satiety: Consider a prokinetic agent as first-line therapy 1, 2, 3
• Metoclopramide is available but should be used with extreme caution due to risk of tardive dyskinesia (TD), which can be irreversible 6
• Critical warning: Metoclopramide should not be used for more than 12 weeks due to increasing risk of TD with duration of treatment 6
• The risk of TD is higher in elderly patients, women, and diabetics 6
• Cisapride is no longer recommended due to cardiac toxicity 1
• Alternative prokinetics include acotiamide, itopride, and mosapride where available 4

Second-Line Treatment for Refractory Symptoms

When Initial Therapy Fails

• If symptoms persist after 2-4 weeks of initial therapy, switch treatment class (e.g., from PPI to prokinetic or vice versa) 1, 5
• Consider a trial of high-dose PPI therapy to confirm acid-related nature of symptoms, including misclassified GERD patients 1

Tricyclic Antidepressants

• Low-dose tricyclic antidepressants (TCAs) are recommended as second-line therapy, particularly for epigastric pain syndrome 1, 3, 4
• Start with amitriptyline 10 mg once daily at bedtime and titrate slowly to a maximum of 30-50 mg once daily 1, 4
• Provide careful explanation of the rationale for their use and counsel patients about side effects 1
• TCAs may be effective for visceral hypersensitivity 7

Antipsychotics (Third-Line)

• Sulpiride 100 mg four times daily or levosulpiride 25 mg three times daily may be efficacious as second-line treatment 1
• Require careful explanation of rationale and counseling about side effect profile 1

Non-Pharmacological Treatment Modalities

Lifestyle and Dietary Modifications

• Regular aerobic exercise is strongly recommended for all patients with functional dyspepsia 1, 2, 3, 4
• Patients should avoid foods that trigger symptoms, but avoid overly restrictive diets that could lead to malnutrition 1, 2, 3
• Early dietitian involvement is recommended in severe or refractory cases to prevent excessively restrictive diets 1, 2, 3
• Dietary changes include frequent small meals, low-fat diet, cessation of smoking, avoiding excess alcohol, and minimizing coffee intake 7
• There is insufficient evidence to recommend specialized diets, including low FODMAP diets, for functional dyspepsia 3

Psychological and Behavioral Interventions

• In patients with resistant functional dyspepsia where symptomatic therapy fails, re-evaluate the diagnosis, provide reassurance, and consider behavioral therapy, psychotherapy, or antidepressants 1, 2

Management of Severe or Refractory Functional Dyspepsia

Multidisciplinary Approach

• A multidisciplinary support team including primary care physicians, dietitians, gastroenterologists, and psychologists should be involved for patients with severe or refractory functional dyspepsia 1, 2, 3

Critical Safety Warnings

• Opioids and surgery must be avoided in patients with severe or refractory functional dyspepsia to minimize iatrogenic harm 1, 2, 3
• Patients with severe functional dyspepsia presenting with weight loss and food restriction should be assessed for eating disorders, including avoidant restrictive food intake disorder (ARFID) 1, 2, 3

Specialist Referral Indications

• Refer to gastroenterology when there is diagnostic doubt, symptoms are severe or refractory to first-line treatments, or for endoscopy 3
• Endoscopy provides a positive diagnosis of functional dyspepsia and allows treatment according to the most bothersome symptom 1

Treatment Maintenance and Follow-Up

• If symptoms are controlled by initial empirical therapy, consider a trial of withdrawal with therapy repeated if symptoms recur 1
• On-demand therapy with the successful agent is an option, though data are limited in functional dyspepsia 1
• For patients on long-term PPI therapy (>3 years), monitor for potential complications including cyanocobalamin (vitamin B12) deficiency, hypomagnesemia, and increased risk of osteoporosis-related fractures 8
• Use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated 8

Common Pitfalls to Avoid

• Do not assume symptomatic response to PPI therapy excludes gastric malignancy in adults; consider additional follow-up and diagnostic testing in those with suboptimal response 8
• Do not routinely perform gastric emptying testing or 24-hour pH monitoring in patients with typical functional dyspepsia symptoms 3
• Avoid combining prokinetic agents with other medications that may prolong the QT interval 3, 4
• Do not prescribe metoclopramide without discussing the risk of tardive dyskinesia and limiting treatment duration to less than 12 weeks 6