Dyspepsia and Peptic Ulcer Disease

Dyspepsia is pain or discomfort centred in the upper abdomen, often accompanied by nausea, early satiety, fullness, or bloating. It is distinct from heartburn and regurgitation, which are symptoms of gastroesophageal reflux disease rather than dyspepsia. Dyspepsia is the cardinal symptom of peptic ulcer disease (PUD) — a break in the mucosa of the stomach (gastric ulcer) or proximal duodenum (duodenal ulcer) — but most patients investigated for chronic dyspepsia have a normal endoscopy; this group is termed functional dyspepsia (FD), further split into epigastric pain syndrome (EPS, pain not clearly related to meals) and postprandial distress syndrome (PDS, discomfort or fullness after eating).^[1] The two dominant causes of PUD are Helicobacter pylori infection and NSAID or ASA use (including low-dose ASA for cardiovascular prophylaxis) — a meaningful minority of ulcers occur without either cause identified. Because PUD and functional dyspepsia cannot be reliably distinguished by symptoms alone, initial management of uninvestigated dyspepsia follows a structured test-and-treat/empiric-therapy pathway rather than attempting to guess the underlying cause clinically.^[2]

Uninvestigated dyspepsia

Epigastric pain or discomfort lasting at least one month, often with associated fullness, early satiety, nausea, or bloating. Duodenal ulcer pain classically improves with food and recurs 2-3 hours after eating or at night; gastric ulcer pain is more often worsened by food. In practice this pattern is unreliable for distinguishing PUD from functional dyspepsia and should not be relied upon diagnostically.

Peptic ulcer disease

May present with epigastric pain as above, or entirely silently — this is common with NSAID-induced ulcers, which frequently present for the first time with a bleeding or perforation complication rather than antecedent pain. Physical examination is usually normal or shows only mild epigastric tenderness; a normal exam does not exclude PUD.

The two subtypes commonly overlap in the same patient and both are diagnoses of exclusion made only after endoscopy (or empiric management, in patients under 60 without alarm features) has not identified an organic explanation.^[1]

• Helicobacter pylori infection — the single most common identifiable cause of PUD worldwide.
• NSAID use, including over-the-counter formulations, and low-dose ASA for cardiovascular prophylaxis.
• Concomitant use of corticosteroids, antiplatelet agents (clopidogrel, ticagrelor), anticoagulants (warfarin, direct oral anticoagulants), or SSRIs alongside an NSAID or ASA — each additive to ulcer/bleeding risk.
• Age over 65, and especially over 70.
• High-dose or multiple concurrent NSAIDs.
• Prior history of gastric or duodenal ulcer or upper GI bleeding.
• Severe medical comorbidity — heart failure, COPD, chronic renal or hepatic disease, advanced malignancy.
• Smoking.
• Other medications that can cause or aggravate dyspepsia: bisphosphonates, calcium channel blockers, erythromycin and other macrolides, iron salts, metronidazole, tetracyclines, and opioids (particularly codeine).
• For functional dyspepsia specifically: female sex, smoking, and an overlying anxiety or mood disorder are each associated, though a specific cause is often not identifiable.

Dyspepsia versus GERD — differentiating on presentation

History

• Exclude non-GI sources of upper abdominal pain — ischemic heart disease, biliary or pancreatic disease, pulmonary disease.
• Full medication history, including OTC, herbal, and supplement use, focused specifically on NSAID/ASA use (including low-dose ASA) and the other dyspepsia-aggravating drugs listed under Risk Factors.
• Screen explicitly for every alarm feature above at every assessment, not only at the first visit.

When endoscopy is and is not indicated

Endoscopy is indicated for any new-onset dyspepsia at age 60 or older, and should be considered case-by-case below that age when alarm features are present.^[2] Endoscopy allows direct visualization and biopsy and is the most sensitive and specific test available, but is not required to initiate management in a younger patient without alarm features — that patient should proceed directly to the test-and-treat/empiric-therapy pathway described in Choose Initial Treatment. Upper GI barium studies are not recommended for investigating dyspepsia given a substantial false-positive and false-negative rate; Choosing Wisely Canada specifically recommends against this test for this indication.

H. pylori testing

• Urea breath test (UBT) — highly sensitive and specific; the preferred non-invasive test where available. Requires stopping antibiotics/bismuth for 4 weeks and PPIs/H2RAs for at least 1-2 weeks beforehand to avoid a false negative.^[3]
• Fecal (stool) antigen test — comparably accurate to UBT, requires a stool sample, and is similarly affected by recent acid-suppressive therapy.^[3]
• Serology (IgG) — appropriate only when there has been no prior eradication attempt; not affected by recent PPI/antibiotic use, but cannot be used to confirm eradication since it can remain positive for years after successful treatment.
• Endoscopic biopsy (rapid urease test, histology) — the gold-standard invasive option; reserved for patients already undergoing endoscopy for another indication rather than performed solely for H. pylori diagnosis.

All patients diagnosed with PUD — regardless of NSAID/ASA use — should be tested for H. pylori and treated if positive.^[4]

• Relieve and prevent symptoms of dyspepsia.
• Confirm and eradicate H. pylori as a potential underlying cause.
• Heal active PUD and prevent its recurrence.
• Prevent PUD-related complications — bleeding, perforation, obstruction — in patients on ongoing ASA or NSAID therapy.
• Confirm H. pylori eradication with the correct test at the correct interval whenever eradication was attempted.
• Avoid indefinite, unreviewed PPI therapy once the original indication has resolved.

• Advise moderation of foods/beverages that reproducibly worsen symptoms — coffee, orange juice, alcohol, spicy or fatty foods, large meals, or eating on the run.
• Recommend avoiding non-prescription products containing ASA or NSAIDs, which can cause or worsen both dyspepsia and PUD.
• Eating smaller, more frequent meals and reducing high-fat food intake can help functional dyspepsia, particularly postprandial distress syndrome.
• Reassure and educate functional dyspepsia patients about the benign nature of the condition — this itself has therapeutic value, since anxiety about a missed serious diagnosis can perpetuate symptoms.
• Refer for psychological therapy (e.g., cognitive behavioural therapy) when there is an overlying mood or anxiety disorder, or when functional dyspepsia has not responded to sequential drug therapy.
• Smoking cessation counselling.

Breastfeeding

PPIs and H2RAs are compatible with breastfeeding at usual doses. Metronidazole (a component of both bismuth quadruple therapy and BV/trichomoniasis regimens) is compatible with breastfeeding; some clinicians advise withholding breastfeeding for 12-24 hours specifically after a single large dose, though this does not apply to the divided daily dosing used in H. pylori regimens.

Pediatrics

Uninvestigated dyspepsia and H. pylori management in children should be directed by a pediatric gastroenterologist rather than managed with the adult algorithm in this chapter — pediatric PPI/H2RA dosing for PUD and H. pylori eradication is weight-based and not established for routine primary-care initiation.

Renal and hepatic impairment

PPIs generally require no dose adjustment in renal impairment. H2RAs (famotidine, nizatidine, cimetidine) require dose reduction in significant renal impairment given increased CNS adverse effect risk (confusion, especially in older adults). Metronidazole and tetracycline require dose adjustment or avoidance in significant hepatic or renal impairment respectively — confirm before starting any H. pylori eradication regimen in a patient with organ impairment.

Older adults

Higher baseline risk of NSAID-related GI complications (age over 65 is itself a risk-stratification criterion) and higher risk of H2RA-related confusion. Long-term PPI use should be reviewed at least annually for ongoing indication given accumulating observational associations with fracture, hypomagnesemia, and enteric infection risk — see Monitoring & Follow-Up.

Reassess symptom response 4-8 weeks after starting an empiric PPI trial or completing an H. pylori eradication regimen; persistent or recurrent symptoms should prompt the next step in the sequence described in Choose Initial Treatment rather than simply repeating the same therapy. Confirm H. pylori eradication specifically in patients with a history of complicated PUD (bleeding, perforation, obstruction) and in anyone with ongoing or recurrent dyspepsia after treatment — testing (UBT or stool antigen; never serology) should occur at least 4 weeks after finishing antibiotics and bismuth, and at least 1-2 weeks after stopping the PPI (bridge with an H2RA or antacid during this interval if acid suppression is still needed).^[4] Review every patient on long-term PPI therapy at least annually: confirm the original indication still applies, and attempt a trial discontinuation, dose reduction, or step-down to on-demand/H2RA therapy where appropriate — an indefinite PPI prescription without periodic reassessment is not appropriate management.^[8] Recheck hemoglobin/ferritin if iron-deficiency anemia prompted the original workup.

1. Confirm adherence to the full prescribed regimen (correct drugs, doses, and duration) before assuming true treatment failure.
2. For suspected H. pylori eradication failure, confirm with UBT or stool antigen testing (not serology) at the correct interval — do not retreat empirically without confirming persistent infection.
3. If H. pylori eradication genuinely failed, switch to a different regimen class rather than repeating the same one — for example, move from bismuth quadruple therapy to rifabutin triple therapy, or vice versa.^[4]
4. After two failed eradication attempts, obtain culture-based susceptibility testing where available, or refer to gastroenterology for tailored salvage therapy.
5. If PPI empiric therapy for uninvestigated dyspepsia fails and endoscopy has not yet been performed, reconsider whether endoscopy is now warranted, particularly if any alarm feature has since developed.
6. For functional dyspepsia not responding to the full PPI → TCA → prokinetic sequence, offer psychological therapy and reconsider the diagnosis — a missed motility disorder (gastroparesis) or an alternative cause should be considered in refractory cases.
7. For NSAID-associated PUD that recurs despite an NSAID being stopped and a PPI given, confirm H. pylori has been tested for and treated, and consider whether the NSAID or ASA source (including OTC use) has truly been eliminated.

• Using clarithromycin-containing triple therapy as first-line, empiric H. pylori treatment — current resistance rates make this an unreliable choice unless susceptibility is confirmed.
• Using serology to confirm H. pylori eradication — it can remain positive for years after successful treatment and will produce a false impression of ongoing infection.
• Substituting doxycycline for tetracycline in bismuth quadruple therapy — this measurably lowers eradication rates and should be avoided when tetracycline is obtainable.
• Testing for H. pylori eradication too soon — before 4 weeks off antibiotics/bismuth or 1-2 weeks off PPI therapy — which risks a false-negative result.
• Requiring endoscopy before starting management in an uninvestigated dyspepsia patient under 60 without alarm features — this delays effective test-and-treat/empiric therapy without added benefit.
• Continuing an NSAID indefinitely in a high-GI-risk patient without gastroprotection, or assuming a COX-2 inhibitor alone (without a PPI) is sufficient protection in a very-high-risk patient.
• Stopping low-dose ASA prescribed for cardiovascular prophylaxis after a bleeding ulcer instead of continuing it with PPI cover — discontinuation trades a GI risk for a cardiovascular one.
• Leaving a patient on long-term PPI therapy indefinitely without an annual reassessment of ongoing indication.
• Missing an alarm feature in a patient under 60 because dyspepsia was assumed to be routine and low-risk.

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Proton pump inhibitors

Any agent in this class is an acceptable choice for empiric dyspepsia trials, PUD healing, and NSAID gastroprotection at standard dose; higher BID dosing applies specifically within H. pylori eradication regimens. Duodenal ulcer healing course is 4-8 weeks; gastric ulcer healing course is 8-12 weeks.

Histamine H2-receptor antagonists

Alternative to a PPI for symptom control and step-down maintenance; less effective than a PPI for active PUD healing or NSAID gastroprotection. Ranitidine is not included — it has had limited/discontinued Canadian availability since 2019-2020 nitrosamine (NDMA)-related recalls.

Helicobacter pylori eradication — bismuth quadruple therapy (preferred 1st line)

Optimized regimen per the 2024 ACG guideline: bismuth, tetracycline, and metronidazole each at full labeled frequency, for a full 14 days — shortening duration or substituting doxycycline for tetracycline measurably reduces eradication rates.

Helicobacter pylori eradication — rifabutin triple therapy

Reasonable 1st-line alternative, or salvage therapy after bismuth quadruple therapy failure. Rifabutin resistance in H. pylori is currently rare.

Helicobacter pylori eradication — clarithromycin triple therapy (restricted use)

Do not use empirically. Reserve for confirmed clarithromycin-susceptible infection, or documented and monitored local resistance under 15%.

Helicobacter pylori eradication — salvage/component agents

Used within a quadruple or rescue regimen once first-line therapy has failed and reinfection/nonadherence have been excluded.

Potassium-competitive acid blocker (PCAB) dual therapy

Vonoprazan-amoxicillin dual therapy is recognized as a reasonable 1st-line alternative by the 2024 ACG guideline internationally; as of this writing vonoprazan is not established as broadly available in the Canadian market — confirm local availability before selecting this option.

Mucosal protective / prokinetic / neuromodulator agents

Used for NSAID ulcer prevention (misoprostol, sucralfate) or functional dyspepsia (prokinetics, neuromodulators) rather than for H. pylori eradication.

NSAID-sparing / gastroprotective options

For patients requiring ongoing anti-inflammatory therapy who are at moderate-to-high GI risk.

Evidence note: Rifabutin triple-therapy dosing (rifabutin capped at 150 mg/day) reflects the pivotal RHB-105 trial design, which deliberately used this low dose to minimize myelosuppression risk relative to the higher, longer-course rifabutin regimens used for tuberculosis or Mycobacterium avium complex.^[10] NSAID/ASA gastrointestinal risk stratification (low/moderate/high risk categories and the corresponding gastroprotection strategy) follows the ACCF/ACG/AHA expert consensus framework.^[11]