Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD) is defined as reflux of stomach contents that causes troublesome symptoms and/or complications.^[1] The underlying mechanism is incompetence of the gastroesophageal junction — the lower esophageal sphincter (LES) together with the surrounding diaphragmatic crura — most often driven by frequent transient LES relaxations, and often worsened by a hiatal hernia. The severity of symptoms and the degree of esophageal mucosal injury generally correlate with how long the esophageal mucosa is exposed to acid (pH under 4) over a 24-hour period, not with symptom intensity alone.^[2]

GERD matters clinically for two separate reasons: its direct effect on quality of life through heartburn and regurgitation, and the potential for long-term esophageal complications — erosive esophagitis, peptic stricture, and Barrett esophagus, which carries a risk of progression to esophageal adenocarcinoma. Most patients who report reflux symptoms have no visible mucosal injury on endoscopy.

Typical presentation

Heartburn (a retrosternal burning sensation, often worse after meals, when lying flat, or when bending forward) and regurgitation of acid or bile are the two hallmark symptoms; hypersalivation ("water brash") and noncardiac chest pain also occur. Heartburn and regurgitation are highly specific for GERD when present, but their absence does not reliably exclude it — pathological acid reflux can occur without classic symptoms.^[2]

Globus versus dysphagia — a distinction that changes management

Globus (a continuous lump-in-the-throat sensation that does not interfere with swallowing) is a minor, common feature of reflux that does not require investigation and usually responds to effective acid suppression. Dysphagia (actual difficulty swallowing) is a different symptom entirely and is an alarm feature requiring endoscopic evaluation — see Red Flags & Refer.

Practically, extraesophageal manifestations include airway symptoms (cough, wheezing), oropharyngeal symptoms (hoarse voice, sore throat, globus sensation, oropharyngeal ulceration), dental enamel erosion, and burning mouth syndrome. These can occur even when typical heartburn/regurgitation is minimal or absent, which is why a purely symptom-based approach can miss extraesophageal GERD.

• Hiatal hernia.
• Obesity — BMI over 30 kg/m2, or a recent significant weight gain, even without a high baseline BMI.
• Pregnancy.
• Esophageal dysmotility (e.g., scleroderma).
• Smoking.
• Alcohol use.

Medications that promote reflux (reduce LES tone or impair esophageal motility)

Review the medication list for the following classes whenever GERD is new, worsening, or refractory, and eliminate or substitute where clinically appropriate:

• Alpha-adrenergic agonists.
• Anticholinergic agents.
• Beta-adrenergic agonists.
• Calcium channel blockers.
• Estrogen.
• Nitrates.
• Opioids.
• Theophylline.
• Tricyclic antidepressants.

Additional risk factors for progression to Barrett esophagus

• Chronic GERD itself is the major risk factor.
• Male sex.
• White race or ethnicity.
• Age 50 years or older.
• Abdominal obesity.
• Family history of Barrett esophagus or esophageal adenocarcinoma.
• Smoking.

Differentiating GERD from its common mimics

Reflux-type symptoms and noncardiac chest pain have several distinct causes that can present similarly but need different management — differentiate before committing to escalating acid suppression.^[3][4]

History

• History alone is usually sufficient for diagnosis when symptoms are typical: heartburn, regurgitation of acid or bile, hypersalivation ("water brash"), and noncardiac chest pain.
• Ask specifically about extraesophageal manifestations — cough, wheezing, hoarse voice, sore throat, globus sensation or ulceration, dental enamel erosion, burning mouth syndrome.
• Ask about esophageal complications — dysphagia (suggesting a peptic stricture), or odynophagia/GI bleeding (suggesting esophageal ulceration).
• Identify predisposing/associated conditions — hiatal hernia, obesity, pregnancy, esophageal dysmotility (e.g., scleroderma).
• Screen for every alarm feature in Red Flags & Refer before starting empiric therapy.

When to order upper endoscopy

Upper endoscopy is generally not required when GERD features are typical and no alarm feature is present — an empiric PPI trial is both treatment and, if symptoms respond, diagnostic confirmation.^[2]

Order upper endoscopy for any of the following:

• Any alarm feature (see Red Flags & Refer).
• Refractory GERD — heartburn and reflux symptoms that persist despite an optimized twice-daily PPI trial (dosed 30-60 minutes before meals) for 4-8 weeks.
• Suspicion of a different cause of esophagitis — eosinophilic, pill-induced, or infectious esophagitis.
• To confirm the diagnosis when response to an empiric trial is unclear or when planning long-term management, since endoscopy also stages any erosive esophagitis present (Los Angeles grade) and identifies Barrett esophagus if present.

Chronic GERD is the major risk factor for Barrett esophagus, but current Canadian guidance recommends against routine endoscopic screening for esophageal adenocarcinoma or Barrett esophagus in adults with chronic GERD who do not have alarm features — this recommendation does not apply to patients who already have alarm features or a confirmed diagnosis of Barrett esophagus/dysplasia, who need endoscopic follow-up on its own schedule.^[5]

Ambulatory pH and impedance monitoring

Indicated for atypical reflux symptoms where the diagnosis is unclear, and for patients who fail standard medical therapy. It can detect abnormal acid reflux even when esophagitis is absent (as in NERD), correlate symptom episodes with actual reflux events, and determine whether therapy is adequately controlling reflux. The Lyon Consensus 2.0 (2024) update to modern GERD diagnostic criteria now allows Los Angeles grade B esophagitis (previously grade C or higher was required) to independently confirm a GERD diagnosis on endoscopy, alongside acid-exposure-time thresholds on pH/impedance testing.^[3]

Testing not indicated

Testing for Helicobacter pylori is not necessary in GERD patients. H. pylori infection has an inverse relationship with GERD complications — the associated chronic gastritis may lower gastric acidity — so eradication is not part of routine GERD management, though it remains indicated for its own reasons (e.g., confirmed peptic ulcer disease).

• Relieve symptoms — particularly heartburn and regurgitation — and improve quality of life.
• Promote healing of erosive esophagitis when present.
• Prevent complications: stricture formation, bleeding, and progression to Barrett esophagus or extraesophageal problems.
• Prevent recurrence once symptom control is achieved.

• Modify diet — avoid chocolate, caffeine, acidic citrus juices, and large, fatty meals.
• Reduce body weight if BMI is over 30 kg/m2, or following a recent weight gain, even without a high baseline BMI.
• Avoid eating within 3 hours of bedtime.
• Avoid lying down right after meals.
• Elevate the head of the bed by 10-20 cm, particularly for nocturnal or laryngeal reflux symptoms — best achieved with a block under the bed frame's legs, not with extra pillows or a wedge, which raises only the upper body rather than the whole thorax.
• Stop smoking.
• Avoid alcohol.
• Avoid tight-fitting clothing around the abdomen.
• Review the medication list for drugs that lower LES tone or impair esophageal motility (see Risk Factors) and eliminate or substitute where clinically appropriate.

These lifestyle measures have the best supporting evidence when applied together rather than individually.^[2] Counsel patients that antacids and alginates provide fast but short-lived relief and do not heal esophagitis or prevent complications — appropriate for mild, infrequent symptoms, but not a substitute for scheduled acid-suppressing therapy in moderate-to-severe disease.

Breastfeeding: Antacids are not concentrated in breast milk and are considered safe. Alginates are also safe. H2RAs and PPIs are both considered compatible with breastfeeding — any small amount of a PPI passing into breast milk is likely destroyed in the infant's stomach by acid hydrolysis, and famotidine is preferred over other H2RAs given its minimal interaction profile and more established safety data.

Pediatrics

Physiologic reflux (frequent "spitting up" without other concerning features) is extremely common in infancy and typically resolves on its own by 12-18 months of age without treatment. Poor weight gain or failure to thrive, forceful or bilious vomiting, blood in the stool or vomitus, and respiratory symptoms in an infant are red flags warranting pediatric GI referral rather than empiric acid suppression. Empiric acid-suppressing therapy for infant fussiness or crying without other reflux features is not supported by evidence and exposes the infant to unnecessary risk. Pediatric GERD in older children, and pharmacologic treatment when genuinely indicated, is managed per separate pediatric-specific dosing and guidance — this chapter's recommendations are written for adult GERD.

Older adults

Older adults are more likely to have atypical presentations (dyspepsia, dysphagia, or respiratory symptoms without prominent heartburn), and new-onset reflux symptoms at age 60 or older is itself an alarm feature warranting endoscopy rather than an empiric trial (see Red Flags & Refer). Older adults are also more susceptible to the long-term risks of chronic PPI therapy and are frequently on multiple interacting medications, making an annual deprescribing review particularly valuable in this group.^[6]

Renal and hepatic impairment

Omeprazole should not exceed 20 mg/day in significant hepatic impairment. H2RAs require renal dose reduction — reduce famotidine, nizatidine, and ranitidine doses (or extend the dosing interval) in significant renal impairment, and reduce cimetidine dosing in renal impairment given its already extensive interaction profile. Avoid regular, high-dose aluminum- or magnesium-containing antacids/alginates in significant renal impairment because of accumulation risk, and avoid regular high-dose calcium carbonate in renal impairment given hypercalcemia risk.

Reassess symptom response at 4-8 weeks after starting an 8-week PPI trial. If well controlled, decide between continuing maintenance therapy (severe erosive esophagitis, Barrett esophagus, GI bleeding history) versus attempting step-down, on-demand dosing, or discontinuation (NERD, milder disease).

For anyone remaining on long-term PPI therapy, reassess the ongoing indication at least annually — through an actual trial of dose reduction or discontinuation, not simply a chart review — except in Barrett esophagus, severe erosive esophagitis (LA grade C/D), or a history of GI bleeding, where long-term maintenance is appropriate and an annual discontinuation attempt is not indicated.^[6][7]

For patients remaining on long-term PPI therapy, periodically review the real, evidence-associated risks of prolonged acid suppression and counsel accordingly — this is informational counselling, not a reason to withhold indicated therapy: vitamin B12 deficiency (reduced absorption of protein-bound B12 — check levels if symptoms of deficiency develop, particularly in older adults or after several years of continuous use), hypomagnesemia (can present with fatigue, muscle cramps, arrhythmia, or seizures — consider checking magnesium periodically in patients on other magnesium-wasting drugs, such as diuretics, or after prolonged therapy), increased fracture risk (counsel on adequate calcium/vitamin D intake and weight-bearing exercise; do not withhold PPI therapy from a patient who needs it, but do not continue it indefinitely without an ongoing indication either), and increased risk of Clostridioides difficile and other enteric infections (reinforce standard infection-prevention counselling, and reconsider ongoing PPI necessity in a patient with recurrent C. difficile).^[8]

Community-acquired pneumonia and other associations raised in epidemiological literature (chronic kidney disease, cardiovascular events, dementia) do not have an established causal relationship with PPI use — mention them as part of a balanced long-term risk discussion without overstating certainty.^[8]

1. Confirm adherence and correct administration technique first — PPIs must be taken 30 minutes before a meal, not with or after food, and not combined with an H2RA on the same schedule (concurrent H2RA use can blunt PPI efficacy by reducing parietal cell acid-pump activation).
2. Optimize the PPI trial: increase from once-daily to twice-daily dosing (30-60 minutes before meals), or switch to a delayed-release formulation (dexlansoprazole) for improved 24-hour coverage. Further dose escalation beyond twice-daily has no added value.
3. Consider an empiric switch to a different PPI — not fully substantiated by evidence, but some individuals respond better to one agent than another.
4. For nocturnal acid breakthrough despite twice-daily PPI therapy, add a bedtime H2RA — use it intermittently or on-demand rather than continuously, since tolerance develops quickly with regular H2RA use.
5. If symptoms persist despite an optimized twice-daily PPI trial, pursue further investigation rather than continued empiric escalation: upper endoscopy with biopsies (performed off PPI therapy), ambulatory pH/impedance monitoring, and esophageal manometry.
6. If GERD is excluded by this workup, discontinue PPI therapy and evaluate for the actual cause — functional heartburn, achalasia or diffuse esophageal spasm, eosinophilic or pill-induced esophagitis, functional dyspepsia, peptic ulcer disease, biliary tract disease, or ischemic heart disease.
7. If GERD is confirmed but remains refractory to optimal medical therapy, refer for a mechanical/procedural evaluation — laparoscopic fundoplication is the current surgical standard; transoral incisionless fundoplication and magnetic sphincter augmentation are newer options whose long-term safety and efficacy are still being established. Indications include intractable esophagitis despite optimal medical therapy (particularly in a younger patient), PPI intolerance, or a complication such as severe erosive esophagitis, stricture, or recurrent aspiration pneumonia.

• Using a PPI "as needed" or sporadically — onset is not immediate (meaningful relief can take more than a single dose), so as-needed dosing does not provide adequate acid inhibition; a scheduled trial is required to properly assess response.
• Taking a PPI with or after food, rather than 30 minutes before a meal — this significantly reduces effectiveness, since PPIs require an activated proton pump to bind.
• Combining a PPI and an H2RA on the same schedule — taking them together can blunt the PPI's effect rather than adding to it.
• Using an H2RA continuously as long-term maintenance therapy — tachyphylaxis develops quickly; H2RAs are best used intermittently, on-demand, or as a bedtime add-on.
• Attempting deprescribing or a discontinuation trial in a patient with Barrett esophagus, severe erosive esophagitis (LA grade C/D), or a GI bleeding history — these patients need long-term maintenance PPI therapy, not an annual step-down attempt.
• Never attempting a discontinuation or step-down trial in a patient who has been on stable, effective PPI therapy for years by default — long-term PPI use should be reassessed at least annually, not simply continued indefinitely without review.
• Missing an alarm feature and treating empirically instead of referring for endoscopy — new dysphagia, GI bleeding, unintentional weight loss, or new-onset symptoms at age 60 or older need investigation, not a longer empiric trial.
• Recommending or dispensing ranitidine or nizatidine without checking current Health Canada recall status — most ranitidine products were recalled over nitrosamine (NDMA) contamination, and famotidine is preferred where an H2RA is needed.^[9]
• Missing a reversible drug-induced contributor — a medication that lowers LES tone or impairs esophageal motility (see Risk Factors) — when GERD is new or worsening.
• Discussing long-term PPI risks (B12 deficiency, hypomagnesemia, fracture risk, C. difficile) in a way that frightens a patient with a genuine ongoing indication into stopping therapy inappropriately — these are real counselling points for periodic review and monitoring, not a reason to withhold indicated therapy.
• Ordering endoscopic screening for Barrett esophagus in a patient with chronic GERD who has no alarm features — current Canadian guidance recommends against this.

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

Relative efficacy by drug class

Qualitative grading based on controlled-trial evidence, adapted for teaching purposes.^[2]

Proton Pump Inhibitors

Prodrugs requiring an activated proton pump for optimal efficacy — take 30 minutes before a meal (usually breakfast). Effective at standard once-daily doses in most patients; escalate to twice-daily dosing or a delayed-release formulation for partial response. At equivalent doses, all PPIs offer similar symptom relief, healing, and safety — agent selection is mainly about individual response and formulary coverage, not clinically meaningful differences in potency.

Histamine H2-Receptor Antagonists

Onset is faster than PPIs, making them useful for on-demand use in mild, infrequent GERD, or as a bedtime add-on for nocturnal acid breakthrough on a PPI. Not reliably effective for healing erosive esophagitis — do not use as monotherapy for confirmed erosive disease. Regular, continuous use leads to rapid tachyphylaxis — best used intermittently or on-demand for maintenance.

Antacids

Neutralize gastric acid directly for rapid, short-lived relief. Do not heal esophagitis or prevent complications — reserved for mild, infrequent symptoms or as an adjunct between scheduled doses of a scheduled medication.

Alginates

Alginate precipitates into a near-neutral-pH gel raft on contact with gastric acid, physically floating over the postprandial acid pocket and displacing it away from the gastroesophageal junction, so the gel — rather than acid — is what refluxes. More effective than a plain antacid for reflux-specific symptoms, though it still does not heal esophagitis.

Mucosal Protectant (pregnancy-specific niche use)

Minimal systemic absorption; an option in pregnancy/breastfeeding when a non-systemic option beyond antacids/alginates is wanted, though it is not considered effective GERD therapy in general use.