What is the best course of action for a patient with dyspepsia, presenting with bloating and abdominal pain that improves after vomiting, who is already taking Zepbound (Esomeprazole) and has a history of diarrhea and vomiting?

Management of Dyspepsia with Bloating and Abdominal Pain in a Patient on Zepbound

This patient's symptoms are most likely related to Zepbound (tirzepatide), which causes gastrointestinal adverse reactions in 56% of patients, and the appropriate management is to continue Zepbound if tolerable while initiating empirical acid suppression therapy with a proton pump inhibitor (omeprazole 20 mg once daily) and testing for H. pylori. 1, 2

Understanding the Clinical Context

Zepbound's Gastrointestinal Effects

• Nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, and bloating are extremely common with Zepbound, occurring in 56% of treated patients compared to 30% with placebo 2
• The majority of gastrointestinal adverse reactions occur during dose escalation and decrease over time 2
• Only 4.3% of patients on the highest dose (15 mg) discontinue due to gastrointestinal adverse reactions 2
• Since the patient's symptoms are tolerable and she is not new to Zepbound, discontinuation is not necessary 2

Critical Pitfall to Avoid

• Do not attribute all symptoms to Zepbound and delay appropriate dyspepsia evaluation - the patient may have concurrent functional dyspepsia or H. pylori infection that requires specific treatment 1

Diagnostic Approach

Initial Assessment Requirements

• Determine if alarm symptoms are present: weight loss (if age ≥55 years), dysphagia, persistent vomiting, evidence of gastrointestinal bleeding, or family history of gastro-oesophageal cancer 1
• If alarm symptoms present in a patient ≥55 years with weight loss, or >40 years with family history of gastro-oesophageal cancer, urgent endoscopy is warranted 1
• For patients ≥55 years with treatment-resistant dyspepsia or dyspepsia with nausea/vomiting, non-urgent endoscopy should be considered 1

Essential Testing

• All patients with dyspepsia should be offered non-invasive H. pylori testing (stool antigen or urea breath test) 1
• If age ≥55 years, obtain a full blood count 1
• Coeliac serology is recommended only if overlapping IBS-type symptoms are present 1

Treatment Algorithm

Step 1: H. pylori Testing and Eradication

• Test for H. pylori and provide eradication therapy if positive - this is a strong recommendation with high-quality evidence 1
• Eradication therapy is effective for H. pylori-positive dyspepsia and prevents future gastroduodenal disease 1
• Confirmation of eradication is only needed in patients at increased risk of gastric cancer 1

Step 2: Empirical Acid Suppression Therapy

• For patients without H. pylori infection, or those with persistent symptoms after eradication, offer empirical acid suppression therapy 1
• Start omeprazole 20 mg once daily taken 30-60 minutes before breakfast for 4-8 weeks 3
• This is particularly appropriate given the patient's ulcer-like symptoms (epigastric pain improved by vomiting) 3, 4
• PPIs are more effective than H2-receptor antagonists for dyspepsia and represent first-line acid suppression 3

Step 3: Assess Response and Adjust

• If symptoms resolve after 4-8 weeks, attempt to taper to the lowest effective dose 3
• Consider on-demand therapy rather than continuous daily use 3
• If symptoms persist after 4 weeks on once-daily PPI, escalate to twice-daily dosing (omeprazole 20 mg before breakfast and dinner) 3
• If symptoms persist despite twice-daily PPI after 4-8 weeks, consider referral to gastroenterology 1

Step 4: Second-Line Options if PPI Fails

• Tricyclic antidepressants are effective second-line treatment for functional dyspepsia 3, 4, 5
• Start amitriptyline 10 mg once daily at bedtime and gradually increase to maximum 30-50 mg once daily 3
• This addresses visceral hypersensitivity, which may be contributing to symptoms 4, 5

Lifestyle Modifications

Evidence-Based Recommendations

• Advise regular aerobic exercise - this is a strong recommendation for all patients with functional dyspepsia 1, 3
• Avoid specific foods that trigger symptoms, though there is insufficient evidence for specialized diets including low-FODMAP 1
• Restricting diet too much could lead to malnutrition or abnormal eating habits 1

Managing Zepbound-Related Considerations

Monitoring for Complications

• Watch for signs of dehydration and hypotension, which can occur with gastrointestinal adverse events from Zepbound 2
• Hypotension occurred in 1.6% of Zepbound-treated patients versus 0.1% with placebo 2
• If the patient is on antihypertensive medications, monitor blood pressure closely as hypotension risk increases to 2.2% 2

When to Consider Zepbound Adjustment

• Only if symptoms become intolerable or severe complications develop (acute pancreatitis, acute gallbladder disease, acute kidney injury) 2
• The majority of patients who discontinue due to gastrointestinal adverse reactions do so in the first few months - since this patient is not new to Zepbound, continuation is appropriate 2

Patient Communication Strategy

Establishing Effective Management

• Establish an empathic doctor-patient relationship and shared understanding - this reduces healthcare utilization and improves quality of life 1
• Explain that functional dyspepsia is a disorder of gut-brain interaction affected by diet, stress, and emotional responses 1
• Discuss that Zepbound commonly causes these symptoms but they typically improve over time 2
• Reassure that normal test results do not mean there is no cause - the condition involves problems with gut-brain communication 1