What is the treatment for dyspepsia?

Treatment of Dyspepsia

All patients with dyspepsia should first undergo non-invasive testing for Helicobacter pylori and receive eradication therapy if positive, followed by empirical acid suppression with proton pump inhibitors (PPIs) if symptoms persist or if H. pylori testing is negative. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, identify patients requiring urgent evaluation:

• Urgent endoscopy is warranted for 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, 2
• Non-urgent endoscopy should be considered for patients ≥55 years with treatment-resistant dyspepsia or dyspepsia with raised platelet count, nausea, or vomiting 1, 2
• Urgent abdominal CT scanning should be considered in patients ≥60 years with abdominal pain and weight loss to exclude pancreatic cancer 1, 2

First-Line Treatment Algorithm

Step 1: Test and Treat for H. pylori

Test all patients without alarm features for H. pylori using a validated non-invasive test (breath test or stool antigen test) and eradicate if positive. 1, 2 This strategy is particularly preferable in populations with moderate to high H. pylori prevalence (≥10%). 3

• Eradication therapy is effective for H. pylori-positive functional dyspepsia, though adverse events are more common than with control therapy 1
• Successful eradication should only be confirmed in patients with increased risk of gastric cancer 1

Step 2: Empirical Acid Suppression

For H. pylori-negative patients or those with persistent symptoms after successful eradication, initiate PPI therapy. 1, 2

• PPIs are highly effective for functional dyspepsia, particularly for epigastric pain syndrome subtype 1, 2
• Use the lowest dose that controls symptoms, as there does not appear to be a dose-response relationship 1
• Continue treatment for 4-8 weeks initially 3
• Common pitfall: Avoid long-term PPI use beyond what is medically necessary due to risks including fundic gland polyps (especially beyond one year), hypomagnesemia, vitamin B12 deficiency, and increased risk of cutaneous/systemic lupus erythematosus 4

Alternative First-Line Options

Histamine-2 receptor antagonists may be used as an alternative to PPIs, particularly for ulcer-like dyspepsia, and are well tolerated 1

Prokinetic agents may be considered for patients with predominant fullness, bloating, early satiety, or nausea (dysmotility-like dyspepsia). 1 However, availability varies by region:

• Metoclopramide is the only widely available effective prokinetic but carries significant risks 5
• Critical warning: Metoclopramide should not be used for more than 12 weeks due to risk of tardive dyskinesia, an irreversible movement disorder 6
• Risk of tardive dyskinesia increases with duration of treatment, total cumulative dose, elderly patients (especially women), and diabetics 6
• Cisapride is no longer recommended due to cardiac toxicity 1

Lifestyle Modifications

All patients should be advised to take regular aerobic exercise. 1

• Advise patients to avoid foods that trigger symptoms while being cautious not to adopt overly restrictive diets that could lead to malnutrition 2
• There is insufficient evidence to recommend specialized diets, including low FODMAP diets 1, 2

Second-Line Treatment

If Initial Therapy Fails

Switch treatment class: If PPI fails, consider prokinetic; if prokinetic fails, consider PPI. 1 If symptoms persist after switching, consider a trial of high-dose PPI therapy. 1

Tricyclic Antidepressants (TCAs)

TCAs are the recommended second-line therapy, particularly for epigastric pain syndrome. 1, 2

• Start with low doses (e.g., amitriptyline 10 mg once daily at bedtime) 1, 5
• Titrate slowly to a maximum of 30-50 mg once daily 1
• Provide careful explanation about their use as gut-brain neuromodulators, not for depression 1
• Counsel patients about side effect profile before initiating 1
• Can be initiated in primary or secondary care 1

Antipsychotics

Sulpiride 100 mg four times daily or levosulpiride 25 mg three times daily may be efficacious as second-line treatment, though careful explanation and counseling about side effects is required. 1

Management of Treatment Response

If symptoms are controlled by initial therapy, attempt withdrawal after 4-8 weeks. 1, 3

• If symptoms recur, repeat the successful treatment 1
• On-demand therapy with the successful agent is an alternative approach 1

Referral to Gastroenterology

Refer to specialist when there is diagnostic doubt, symptoms are severe or refractory to first-line treatments, or the patient requests specialist opinion. 1

• Endoscopy is not mandatory in those who remain symptomatic as the yield is low; the decision must be based on clinical judgment 3
• Avoid routine gastric emptying testing or 24-hour pH monitoring in patients with typical functional dyspepsia symptoms 1

Management of Severe or Refractory Cases

A multidisciplinary support team should be involved for patients with severe or refractory functional dyspepsia. 1, 2

• Team should include primary care physicians, dietitians, gastroenterologists, and psychologists 2
• Re-evaluate the diagnosis, provide further reassurance, and consider behavioral therapy, psychotherapy, or antidepressants 1
• Critical warning: Avoid opioids and surgery to minimize iatrogenic harm 1
• Assess patients with weight loss and food restriction for eating disorders, including avoidant restrictive food intake disorder (ARFID) 1
• Ensure early dietitian involvement to avoid overly restrictive diets 1

Important Drug Interactions and Precautions

Avoid concomitant use of omeprazole with clopidogrel, as omeprazole inhibits CYP2C19 and reduces clopidogrel's antiplatelet activity even when administered 12 hours apart. 4

Avoid concomitant use of omeprazole with St. John's Wort or rifampin, as these induce CYP2C19/CYP3A4 and substantially decrease omeprazole concentrations. 4

For patients on long-term PPI therapy (>3 years), monitor for cyanocobalamin (vitamin B12) deficiency and consider monitoring magnesium levels, especially in patients taking digoxin or diuretics. 4

Temporarily stop omeprazole at least 14 days before assessing serum chromogranin A (CgA) levels to avoid false positive results in neuroendocrine tumor screening. 4