Initial management of gastroesophageal reflux disease in adults

INTRODUCTION — 

The return of gastric contents into the esophagus (gastroesophageal reflux) can be a normal physiologic process. Most episodes are brief and do not cause problematic symptoms, esophageal injury, or other complications. Gastroesophageal reflux becomes a disease when it causes macroscopic damage to the esophagus or problematic symptoms.

This topic will review the initial management of reflux-like symptoms and gastroesophageal reflux disease (GERD) and the management of recurrent symptoms when treatment is tapered or discontinued. Our recommendations are largely consistent with guidelines from the American Gastroenterological Association and the American College of Gastroenterology [1,2]. The management of other aspects of GERD is discussed separately:

●Management of refractory GERD (see "Approach to refractory gastroesophageal reflux disease in adults")

●Management of extraesophageal manifestations of GERD (see "Laryngopharyngeal reflux in adults", section on 'Treatment' and "Gastroesophageal reflux and asthma")

●Surgical and endoscopic interventions for GERD (see "Surgical treatment of gastroesophageal reflux in adults" and "Radiofrequency treatment for gastroesophageal reflux disease")

PRETREATMENT EVALUATION

Is upper endoscopy indicated? — Evaluation of typical reflux-like symptoms (ie, heartburn or regurgitation) usually does not require upper endoscopy [2,3]. As part of initial management, we perform an upper endoscopy in patients with the following features (table 1):

●Alarm features that suggest a possible gastrointestinal malignancy or structural lesion

●Multiple risk factors for Barrett's esophagus in individuals who have not undergone prior upper endoscopy

●Abdominal or chest imaging with abnormalities noted in the upper gastrointestinal tract that require workup

Evaluation of these individuals is discussed separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Evaluation in selected patients'.)

Upper endoscopy can document objective manifestations of GERD, including esophagitis and complications of longstanding acid reflux, such as peptic stricture or Barrett's metaplasia. Optimal sensitivity of upper endoscopy for diagnosing esophagitis occurs when patients are off acid suppression medications for two to four weeks. However, this is not always feasible in patients with severe reflux-like symptoms.

Upper endoscopy is also a component of subsequent management in selected patients, as discussed separately. (See 'Patients with persistent symptoms' below and "Approach to refractory gastroesophageal reflux disease in adults".)

Assess symptom severity, frequency, and timing — In patients who do not undergo diagnostic upper endoscopy, the frequency and severity of reflux-like symptoms guide initial management. We categorize symptom frequency as intermittent (less than two episodes per week) or frequent (two or more episodes per week). Symptoms are considered mild or moderate/severe based on whether they impair quality of life. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Clinical features'.)

To facilitate lifestyle changes, clinicians should ask about changes in body weight, nocturnal symptoms, postprandial symptoms, and specific foods or behaviors that trigger reflux-like symptoms. (See 'Lifestyle and dietary modification' below.)

COUNSELING AND LIFESTYLE CHANGES

Education and counseling — We counsel all patients regarding the pathophysiology of acid reflux and the role of self-management and lifestyle modification in controlling symptoms. Counseling includes the following messages [4,5]:

●GERD is a multifactorial process that is not caused by acid alone. Reflux-like symptoms can arise from abnormalities in any of the components that modulate symptom perception: esophageal sensitivity to nociceptive and other stimuli; effective esophageal and gastric motility; an intact antireflux barrier, including normal anatomy and function of the lower esophageal sphincter and surrounding crural diaphragm; anxiety; and psychosocial factors.

●We explicitly link management strategies to the relevant aspect of GERD pathophysiology. As an example, clinicians can explain how increased intra-abdominal pressure and gastric distention trigger postprandial symptoms after a large meal and connect this to the rationale for small portion sizes or weight reduction.

●Bidirectional communication between the brain and the gastrointestinal tract (ie, the gut-brain axis) modulates the perception of painful stimuli. Consequently, situational or symptom-related stress or worry can amplify reflux-like symptoms.

Lifestyle and dietary modification — We suggest lifestyle and dietary modification in all patients with reflux-like symptoms. Clinicians should help patients identify symptom triggers and develop an individualized treatment plan that targets the patient's specific triggers and symptoms (table 2) [5,6]. Developing an individualized plan for lifestyle changes avoids overly restrictive advice, engages patients in self-management, and may enhance treatment adherence (table 3).

Components of lifestyle changes include the following:

●Selective limitation of dietary triggers – Clinicians should work with patients to identify specific food triggers and limit or eliminate them. Common dietary triggers include carbonated beverages, spicy foods, fatty or fried foods, excess coffee, and peppermint.

Most adults with GERD can identify specific dietary triggers, and elimination of these may reduce reflux-like symptoms. As an example, in a small study of primary care patients with GERD, 85 percent of participants identified at least one food that triggered reflux-like symptoms, and most experienced symptom improvement after being asked to eliminate their specific trigger foods [7]. Similarly, in a prospective study of 48,308 females, intake of coffee, tea, and soda was associated with a modest and dose-dependent increase in the risk of GERD symptoms [8]. Substituting water for two servings per day of coffee, tea, or soda was associated with small reductions in GERD symptoms.

●Behavioral changes for nocturnal symptoms

•Avoid late meals – Patients with symptoms when recumbent should maintain a three-hour interval between a meal and lying down. Observational studies suggest an association of reflux-like symptoms with dinner-to-bed times of less than three hours [6].

•Left lateral decubitus positioning – Sleeping in the left lateral decubitus position moves the puddle of gastric contents away from the gastroesophageal junction and may minimize reflux that occurs while supine [9,10].

•Elevation of the head of the bed – Elevation of the head end of the bed may improve nocturnal reflux-like symptoms, based on data from systematic reviews of small, mostly nonrandomized studies [5,11-13]. Patients can use six- to eight-inch blocks under the legs at the head of the bed or a foam wedge under the mattress.

●Weight loss – We encourage weight loss for individuals with overweight or obesity and those who have recently gained weight. Evidence suggests that weight loss reduces reflux-like symptoms [14]. As an example, a systematic review of 10 small, randomized trials and cohort studies concluded that weight loss decreased reflux as quantified by esophageal pH-metry and/or symptoms [15].

●Smoking cessation – We encourage all individuals who smoke tobacco to quit. Tobacco smoking increases the risk of reflux-like symptoms by reducing lower esophageal sphincter pressure, triggering coughing, and diminishing salivation. A large, population-based cohort study found that smoking cessation was associated with a reduction in reflux symptoms in the subset of participants with normal body mass index and severe GERD symptoms [16].

●Other measures – Additional interventions may be incorporated into the management plan for selected patients. These measures have a physiologic basis but have not consistently been demonstrated to improve reflux symptoms. They include [6,15,17]:

•Abdominal breathing exercises (diaphragmatic breathing) to strengthen the diaphragmatic component of the antireflux barrier, especially if regurgitation is a major component of the presentation [18,19]

•Increased physical activity, especially in those with overweight or obesity

•Use of oral lozenges or chewing gum to promote salivation, which neutralizes refluxed acid and increases the rate of esophageal acid clearance

•Avoidance of alcohol, which reduces lower esophageal sphincter pressure

•Avoidance of tight-fitting garments to prevent increases in intragastric pressure and the gastroesophageal pressure gradient (see "Pathophysiology of gastroesophageal reflux disease", section on 'The antireflux barrier')

Robust data from randomized trials do not exist for most behavioral interventions. Nonetheless, most lifestyle changes are supported by indirect evidence and/or expert consensus and unlikely to cause significant harm [6,14]. As an example, in a prospective study of 42,955 females, adherence to five antireflux lifestyle factors was associated with lower rates of GERD symptoms (hazard ratio 0.50, 95% CI 0.42-0.59), compared with nonadherence [16]. This association persisted after adjustment for the use of proton pump inhibitors and histamine 2 receptor antagonists. Lifestyle factors included eating a diet rich in whole grains, vegetables, and fruits; maintaining a healthy body weight; not smoking; exercising 30 minutes daily; and drinking no more than two cups of soda, coffee, or tea per day.

INITIAL PHARMACOTHERAPY

Empiric treatment for those who do not undergo endoscopy — Because upper endoscopy is usually not indicated for the evaluation of reflux-like symptoms, initial pharmacologic management of most adults with GERD consists of empiric therapy that is based on symptom frequency and severity (algorithm 1).

Mild, intermittent symptoms — In patients with mild and intermittent reflux-like symptoms (eg, fewer than two episodes per week), we suggest a step-up approach that incrementally increases the potency of therapy until symptoms are adequately controlled. Each "step" starts with a two- to eight-week treatment trial, and if symptoms persist, the intensity of treatment "steps up" to the next level. Because many of these medications are available without a prescription, clinicians should ask patients about their use of these agents and their effectiveness and start with a medication more potent than agents that had been tried and found ineffective.

Once symptom control occurs, we continue treatment for at least eight weeks. A step-up approach minimizes medication overuse and side effects because up to 40 percent of individuals with GERD will respond to treatment with lifestyle modifications and as-needed antacids, alginates, or histamine 2 receptor antagonists (H2RAs) [20].

In individuals who are treatment naïve, we follow the following sequence of steps to achieve symptom control:

●As-needed antacids, alginates, or histamine 2 receptor antagonists – In treatment-naïve individuals, we start with lifestyle modifications and as-needed treatment with antacids, sodium alginate, and/or low-dose H2RAs for four weeks (table 4) (see 'Lifestyle and dietary modification' above). The selection between these agents depends primarily on patient preference.

•Antacids – Antacids provide immediate, but brief, symptom relief. They relieve symptoms within five minutes of administration, but their effects last only 30 to 60 minutes. Antacids do not prevent reflux. Instead, they combine a magnesium salt, aluminum hydroxide, or calcium carbonate (eg, aluminum hydroxide-magnesium hydroxide) to neutralize acid in the stomach and esophagus, thereby reducing esophageal acid exposure. The pharmacology and side effects of antacids are discussed separately. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Antacids'.)

•Alginates – Sodium alginate, usually combined with antacid, alleviates mild reflux-like symptoms, especially postprandial symptoms [21-24]. Sodium alginate is a polysaccharide derived from seaweed that forms a viscous gel gum that floats within the stomach at the gastroesophageal junction and neutralizes the postprandial acid pocket [25].

•Histamine 2 receptor antagonists – H2RAs may be particularly useful for prolonged symptom episodes because they have a longer duration of action than antacids (4 to 10 hours). However, their onset of action is slower (15 to 30 minutes). H2RA side effects and mechanisms of action are discussed separately. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Histamine-2 receptor antagonists'.)

●Twice-daily histamine 2 receptor antagonists – For individuals who have a partial response to intermittent H2RA therapy, we institute standard-dose H2RA therapy for two to four weeks. Stopping the H2RA and starting a standard-dose proton pump inhibitor (PPI) once daily is a reasonable alternative (table 4) (see 'PPI preferred' below). H2RAs more effectively decrease the frequency and intensity of heartburn than antacids or placebo. However, tachyphylaxis to H2RAs can develop within two to six weeks, which limits their utility for daily maintenance therapy [26].

●Daily proton pump inhibitors – For individuals whose symptoms persist despite treatment with intermittent or standing H2RAs, we discontinue H2RAs and start a standard-dose PPI once daily (table 4) (see 'PPI preferred' below). Switching to PPI therapy in these patients is more likely to control symptoms than increasing the dose or duration of treatment of the H2RA or switching to another H2RA [2,20,27].

Severe or frequent symptoms

PPI preferred — In patients with frequent symptoms (two or more moderate-to-severe episodes per week) or severe symptoms that impair quality of life, we suggest lifestyle modifications combined with standard-dose PPI therapy once daily for eight weeks (table 4) (see 'Lifestyle and dietary modification' above). This approach maximizes the likelihood of rapid symptom relief.

The potassium-competitive acid blocker (PCAB) vonoprazan is an alternative for treating individuals with severe or frequent reflux-like symptoms. However, it is expensive, and randomized trials that directly compare vonoprazan with PPIs for symptom relief are currently lacking. We typically use a PCAB only in patients whose symptoms persist after an adequate trial (ie, eight weeks) of a PPI at maximum dosing (table 4). (See 'Vonoprazan as alternative' below.)

●Dosing and selection – Patients should take PPIs once daily, 30 to 60 minutes before breakfast, to maximally inhibit proton pumps. Because PPIs exhibit a cumulative effect with repetitive dosing, daily dosing more effectively inhibits acid, controls symptoms, heals esophagitis, and improves quality of life, compared with sporadic, on-demand therapy. PPIs inhibit gastric acid secretion by covalently binding to and disabling activated hydrogen-potassium (H⁺-K⁺) adenosine triphosphatase (ATPase) pumps. Taking PPIs before eating optimizes drug efficacy by maximizing serum drug levels during periods of peak gastric acid secretion and proton pump activation. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Dose and timing of administration'.)

Different PPIs offer comparable symptom resolution; consequently, the selection of a specific agent depends primarily on patient preference and cost, as discussed separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Selecting a PPI'.)

PPI pharmacology, administration, and adverse effects are discussed separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders".)

●Benefits and risks – PPIs relieve reflux-like symptoms faster and more effectively than H2RAs and are considered safe [2]. Approximately 75 percent of patients receiving empiric treatment for GERD experience symptomatic improvement [27-30]. In a meta-analysis of individuals treated empirically for GERD symptoms, PPIs more effectively induced heartburn remission than H2RAs (68 versus 45 percent; relative risk [RR] 0.66; 95% CI 0.60-0.73) [27].

PPIs have a slower onset of action compared with H2RAs because they are enteric coated and must gain access to the small intestine before absorption. Because they are associated with more potent acid inhibition, they are associated with an increased risk of some intestinal infections from ingested organisms (eg, traveler's diarrhea, Clostridioides difficile). Side effects associated with PPIs are discussed separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Adverse effects'.)

Vonoprazan as alternative — Although we typically use PPIs to treat patients with severe, frequent reflux-like symptoms, vonoprazan is a reasonable alternative. The US Food and Drug Administration (FDA) approved vonoprazan for the treatment of nonerosive GERD in July 2024; it has been used in Japan since 2015.

●Dosing – We typically start vonoprazan 10 mg once daily for four to eight weeks. For individuals with nonerosive GERD, vonoprazan 10 mg daily appears comparable to the 20 mg dose [31]. For patients who prefer intermittent dosing, we use vonoprazan 10 or 20 mg as needed for symptom control.

Vonoprazan has pharmacokinetic and pharmacodynamic advantages over PPIs. It has a rapid onset of action and neutralizes gastric acid after a single dose [31,32]. Vonoprazan has a longer serum half-life than PPIs (7.9 versus 1.5 hours), thereby inhibiting gastric acid secretion for 24 hours.

Although both agents act on the H⁺-K⁺ ATPase, vonoprazan more effectively inhibits gastric acid secretion by blocking the potassium channel of the H⁺-K⁺ ATPase pump and achieving a very high concentration at its site of action. Dosing can occur independently of meals because of its long serum half-life.

●Efficacy – Vonoprazan is more effective than placebo for reducing frequent reflux-like symptoms. Randomized trials supporting its efficacy include the following:

•In a trial of 772 adults with frequent reflux-like symptoms (≥4 days/week) and without erosive esophagitis on upper endoscopy, vonoprazan 10 and 20 mg daily reduced heartburn symptoms more effectively than placebo at four weeks (percentage of heartburn-free days 45, 44, and 28 percent, respectively; p<0.0001) [31]. Treatment differences between vonoprazan and placebo appeared within the first 48 hours.

•In a trial of 207 individuals with chronic, frequent heartburn symptoms and normal endoscopy, on-demand vonoprazan at doses of 10, 20, and 40 mg daily was more likely to provide sustained relief of heartburn episodes than placebo (56, 61, and 70 percent versus 27 percent of episodes with complete, sustained heartburn relief; p<0.0001) [32].

No role for empiric eradication of Helicobacter pylori — We do not routinely screen for H. pylori infection in individuals with reflux-like symptoms [33]. However, we do test in patients who have other indications for H. pylori testing, such as those with a history of peptic ulcer disease or a family history of gastric cancer. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults".)

If H. pylori is diagnosed in the setting of GERD, its eradication may improve symptoms in the subset of patients with antral-predominant H. pylori gastritis. This is discussed separately. (See "Helicobacter pylori and gastroesophageal reflux disease".)

Treatment based on endoscopy findings — For individuals with reflux-like symptoms whose pretreatment evaluation includes endoscopy, we base treatment selection on endoscopic findings (algorithm 2). Relevant endoscopic findings include the presence and grade of esophagitis, presence of histologic or anatomic evidence of chronic esophagitis (eg, Barrett's esophagus, esophageal stricture), and anatomic findings that attest to the integrity of the gastroesophageal junction. The spectrum and frequency of esophagitis in patients with reflux-like symptoms are discussed separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Endoscopic findings'.)

Patients with esophagitis — In patients with erosive esophagitis (Los Angeles [LA] classification B to D), we recommend initial acid suppression therapy with vonoprazan 20 mg once daily for eight weeks. Once-daily therapy with a standard-dose PPI is an accepted alternative (table 4). Both PPIs and vonoprazan offer superior acid suppression and healing of esophagitis, compared with H2RAs.

●Vonoprazan preferred – We suggest vonoprazan over PPIs because it appears superior for healing erosive esophagitis, particularly for patients with high-grade esophagitis (LA C to D). Representative randomized trials evaluating the efficacy of PCABs for individuals with esophagitis are as follows:

•Some data suggest only small differences in clinical efficacy between PCABs and PPIs. In a meta-analysis of six trials, PCABs demonstrated slightly higher rates of esophageal healing at eight weeks, compared with PPIs (96 versus 94 percent; RR 1.02; 95% CI 1.00-1.05) [34]. Rates of heartburn resolution and significant adverse effects were comparable between the two groups. Similarly, a subsequent randomized trial of participants with predominantly low-grade erosive esophagitis reported that the PCAB zastaprazan 20 mg was noninferior to esomeprazole 40 mg for esophagitis healing at eight-week follow-up (98 versus 95 percent; p = 0.18) [35]. Healing rates were higher at four weeks in the zastaprazan group, compared with esomeprazole (95 versus 88 percent; p = 0.026).

•In a subsequent trial of 1024 participants with erosive esophagitis in the United States and Western Europe, vonoprazan 20 mg daily demonstrated higher rates of esophageal healing at eight weeks, compared with lansoprazole 30 mg (93 versus 85 percent; risk difference 8.3 percent; 95% CI 4.5-12.2 percent) [36]. Vonoprazan also demonstrated higher rates of healing at two weeks in those with high-grade esophagitis (LA C and D; 70 versus 53 percent; 95% CI 7.5-27.4 percent).

The FDA approved vonoprazan for the treatment of erosive esophagitis in late 2023.

●PPI therapy as alternative – Standard-dose proton pump inhibitor (PPI) therapy is a reasonable alternative to vonoprazan in individuals for whom the cost of vonoprazan is prohibitive. PPI dosing and agent selection are the same as those described for empiric treatment. (See 'Severe or frequent symptoms' above and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders".)

Because available PPIs demonstrate similar efficacy, we select a PPI based primarily on cost and insurance coverage. In studies analyzing the relative potency of PPIs, as measured by the percentage of the day that they maintained a gastric pH >4, rabeprazole was most potent, pantoprazole was least potent, and other PPIs had comparable potency. It is unclear whether these findings translate into clinically meaningful differences in efficacy [37].

Standard-dose PPI therapy heals erosive esophagitis in up to 86 percent of patients and improves symptoms of heartburn and regurgitation [28]. PPIs heal esophagitis more rapidly and effectively than H2RAs, particularly in those with high-grade esophagitis (LA classification C or D) [2,38]. As an example, in a meta-analysis of 14 trials of participants with erosive esophagitis, healing rates of esophagitis at 12 weeks were higher in those randomized to treatment with standard-dose PPIs, compared with standard-dose H2RAs (82 versus 52 percent; pooled RR 1.59; 95% CI 1.44-1.75) [39].

Patients with Barrett's esophagus — Barrett's esophagus is a complication of chronic GERD. Management of patients with Barrett's esophagus is discussed separately. (See "Barrett's esophagus: Surveillance and management".)

Patients without esophagitis or Barrett's esophagus — We typically prescribe eight weeks of standard-dose PPI therapy once daily for the initial treatment of reflux-like symptoms in patients without endoscopic evidence of erosive esophagitis or Barrett's esophagus (see 'Severe or frequent symptoms' above). This group includes individuals with nonerosive GERD and those with healed esophagitis due to use of PPI therapy prior to endoscopy. The PCAB vonoprazan is an alternative option; however, it is expensive and does not have proven superiority over PPI therapy in this group of patients. (See 'Vonoprazan as alternative' above.)

Although individuals with nonerosive GERD have lower response rates to PPI therapy than those with documented esophagitis, PPIs are still more efficacious than H2RA in these patients [2]. In a meta-analysis of participants with nonerosive GERD, PPIs more effectively induced heartburn remission than both H2RAs (57 versus 45 percent; RR 0.78 for persistent symptoms; 95% CI 0.62-0.97) and placebo (87 versus 62 percent; RR 0.71; 95% CI 0.65-0.78) [27].

PATIENTS WHO RESPOND TO INITIAL TREATMENT

Patients with high-grade esophagitis

Maintenance acid suppression — Patients with high-grade erosive esophagitis (Los Angeles [LA] grade C or D) require maintenance acid suppression with a proton pump inhibitor (PPI) or vonoprazan to maintain esophageal healing, prevent symptom recurrence, and prevent complications [1,2]. This includes individuals with eosinophilic esophagitis or complications related to GERD, such as an esophageal ulcer or stricture [40]. Maintenance acid suppression in individuals with Barrett's esophagus is discussed separately. (See "Barrett's esophagus: Surveillance and management", section on 'Management of acid reflux'.)

For patients on vonoprazan, we decrease the dose to 10 mg daily rather than switch to a PPI. In one randomized trial, vonoprazan 10 or 20 mg was superior to lansoprazole 15 mg for maintenance of healing at six months [36].

The rationale for long-term acid suppression derives from data suggesting that virtually all individuals with LA grade C or D esophagitis will develop recurrent symptoms and esophagitis can recur within two weeks of stopping acid suppression therapy [2].

When patients cannot tolerate or wish to stop medications for acid suppression, we discuss options for procedural or surgical management of GERD. (See "Surgical treatment of gastroesophageal reflux in adults" and "Radiofrequency treatment for gastroesophageal reflux disease".)

Repeat endoscopy

●High-grade esophagitis (LA grade C or D) – Individuals with high-grade esophagitis (Los Angeles [LA] grade C or D) should undergo a follow-up endoscopy after 8 to 12 weeks of PPI or potassium-competitive acid blocker (PCAB) therapy to assess healing and rule out interval development of Barrett's esophagus. Patients without Barrett's esophagus do not need subsequent follow-up endoscopies unless they develop bleeding, dysphagia, or a significant change in symptoms while on effective acid suppression therapy.

●Barrett's esophagus – Subsequent management of patients with Barrett's esophagus is discussed separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Endoscopic findings' and "Barrett's esophagus: Surveillance and management", section on 'Surveillance'.)

Other patients

Taper PPI or PCAB therapy — Individuals without high-grade esophagitis or Barrett's esophagus whose reflux-like symptoms respond to initial treatment with a PCAB or proton pump inhibitor (PPI) should continue therapy for at least eight weeks and then discontinue or taper the medication to the lowest effective dose [40]. Individuals whose symptoms respond to initial treatment with antacids, alginates, and/or histamine 2 receptor antagonists (H2RAs) can continue these medications as needed for symptom control.

Most patients can decrease or stop acid suppression therapy successfully [41-43]. We inform patients that transient symptom recurrence often occurs with PPI discontinuation and provide instructions for managing these symptoms, including continued adherence to lifestyle changes.

●Treatment duration <6 months – In patients on a PPI or PCAB for less than six months, we stop the medication without taper.

●Treatment duration >6 months – In patients on a PPI or PCAB for longer than six months, we taper the dose before discontinuing it to minimize rebound hypersecretion [40]. Tapering consists of incrementally decreasing the potency of therapy until breakthrough symptoms occur. Patients on standard-dose daily PPI therapy can start by decreasing to a low-dose PPI, followed by alternate-day therapy and, finally, PPI discontinuation. Individuals taking vonoprazan can decrease from 20 to 10 mg once daily to alternate days and then stop the medication. Details regarding PPI discontinuation are discussed separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Discontinuing PPIs'.)

Individuals with mild residual symptoms after PPI discontinuation can use on-demand PPIs, H2RAs, or antacids with or without alginates for symptom control [40]. A two-week course of on-demand low- or standard-dose PPIs may be more efficacious than eliminating PPIs entirely. As an example, in a randomized trial of participants with nonerosive reflux disease, on-demand PPI therapy improved symptom remission rates at six months (83 versus 56 percent), compared with placebo [44].

Manage recurrent symptoms — Approximately two-thirds of individuals with nonerosive GERD relapse after stopping acid suppression medications. We reinforce lifestyle and dietary changes with these patients and pursue additional management that varies depending on how soon symptoms recur after stopping medications.

●In patients whose symptoms recur ≥3 months after discontinuing acid suppression, we repeat an eight-week course of acid suppressive therapy using the same medication and dose that previously controlled symptoms [1,2]. We adjust the medication dose and potency to control symptoms and, once they are controlled, taper and discontinue the medication after eight weeks (table 4).

●In patients whose symptoms recur <3 months after discontinuing acid suppression, we resume treatment with the previously effective regimen. These individuals often require continuous maintenance acid suppressive therapy. If patients in this group have not previously undergone upper endoscopy, some experts would pursue additional diagnostic workup. (See "Approach to refractory gastroesophageal reflux disease in adults", section on 'Diagnostic strategies and initial management'.)

The role of surgery and endoscopic therapy in patients with GERD who cannot tolerate or want to stop long-term PPIs are discussed separately. (See "Surgical treatment of gastroesophageal reflux in adults", section on 'Indications' and "Radiofrequency treatment for gastroesophageal reflux disease".)

PATIENTS WITH PERSISTENT SYMPTOMS — 

Up to 40 percent of adults with reflux-like symptoms will have an incomplete response to initial proton pump inhibitor (PPI) or potassium-competitive acid blocker therapy; these patients are considered to have refractory GERD or reflux-like symptoms. We typically refer individuals with refractory reflux-like symptoms to a gastroenterologist for further evaluation and diagnostic endoscopy to differentiate between refractory GERD, reflux hypersensitivity, functional heartburn, or some other disorder [45].

Additionally, we assess for adherence to lifestyle measures; ensure that PPI dosing takes place 30 to 60 minutes prior to breakfast; and evaluate the severity, frequency, and timing of residual symptoms. Individuals whose symptoms significantly improve but do not resolve can use antacids with or without alginates for mild breakthrough symptoms. Patients on a PPI whose symptoms are well controlled during the day but recur in the evening or at night (ie, at the end of the dosing period) may benefit from adding a second dose of the PPI 30 to 60 minutes prior to their evening meal.

Evaluation and management of patients with persistent symptoms are discussed separately. (See "Approach to refractory gastroesophageal reflux disease in adults", section on 'Initial assessment'.)

PATIENTS WHO ARE PREGNANT OR BREASTFEEDING

●Management approach – Initial management of GERD in pregnancy and breastfeeding consists of a "step-up" approach, similar to that of nonpregnant individuals with mild, intermittent symptoms. It starts with lifestyle modifications and as-needed antacids; alginates; and/or sucralfate, 1 g orally three times daily (see 'Counseling and lifestyle changes' above). In patients with persistent symptoms, we add histamine 2 receptor antagonists (H2RAs) and, if symptoms do not resolve, switch H2RAs to proton pump inhibitors (PPIs) (table 4). (See 'Mild, intermittent symptoms' above.)

●Medication considerations – Specific considerations for medications in pregnancy and breastfeeding include the following:

•Antacids and alginates are considered safe in pregnancy and breastfeeding [46]. However, individuals who are pregnant should avoid antacids containing sodium bicarbonate or magnesium trisilicate (not sold in the United States). Sodium bicarbonate can potentially cause metabolic alkalosis and fluid overload in the pregnant person and fetus [47]. Antacids containing magnesium trisilicate have been associated with adverse effects on the fetus when used in high doses and long term [47].

•Sucralfate (aluminum sucrose sulfate) is likely safe during pregnancy and lactation because it is poorly absorbed [47]. It adheres to the mucosal surface, promotes healing, and protects from peptic injury. Its use for GERD is limited to pregnancy because of its short duration of action and limited efficacy [2]. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Sucralfate'.)

•H2RAs are considered safe in pregnancy.

•PPIs appear to be safe in pregnancy. We typically use omeprazole, lansoprazole, or pantoprazole because they have been more widely studied in pregnancy.

A meta-analysis of seven observational studies found no significant difference in the risk of major congenital anomalies, spontaneous abortions, or preterm delivery among 1530 women exposed to PPIs during pregnancy, compared with 133,410 women without PPI exposure [48]. A subsequent large, observational study found no increased risk of major birth defects in infants exposed to PPIs during the first trimester, compared with those who were not exposed [49].

Limited data exist on the secretion of PPIs in breast milk. Although omeprazole and pantoprazole are secreted in low concentrations in breast milk, most of the medication is likely destroyed by gastric acid in the infant's stomach [50-52].

•We avoid vonoprazan in persons who are pregnant or breastfeeding because data are insufficient to confirm the drug's safety in these patients [53].

●Considerations for upper endoscopy – Upper endoscopy should be performed during pregnancy only if a strong indication exists (eg, significant gastrointestinal bleeding). It should be postponed until the second trimester if possible [54]. Obstetrical staff should participate in management decisions and determine the degree of maternal and fetal monitoring. Procedural sedation for endoscopy in pregnant people and people who are nursing is discussed separately. (See "Gastrointestinal endoscopy in adults: Procedural sedation administered by endoscopists", section on 'Special populations'.)

INDICATIONS FOR REFERRAL — 

Indications for referral to a gastroenterologist include:

●Patients with persistent symptoms after initial treatment with proton pump inhibitor (PPI) therapy (see 'Patients with persistent symptoms' above and "Approach to refractory gastroesophageal reflux disease in adults")

●Patients with indications for long-term acid suppression therapy (eg, Barrett's esophagus or severe erosive esophagitis) who cannot tolerate or want to discontinue long-term PPI/potassium-competitive acid blocker therapy (see 'Maintenance acid suppression' above and "Surgical treatment of gastroesophageal reflux in adults" and "Radiofrequency treatment for gastroesophageal reflux disease")

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastroesophageal reflux in adults".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acid reflux and GERD in adults (The Basics)" and "Patient education: H. pylori infection (The Basics)" and "Patient education: Acid reflux and GERD during pregnancy (The Basics)")

●Beyond the Basics topics (see "Patient education: Gastroesophageal reflux disease in adults (Beyond the Basics)" and "Patient education: Helicobacter pylori infection and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Counseling and lifestyle changes – We suggest lifestyle and dietary modification in all patients with reflux-like symptoms (Grade 2C). We counsel patients regarding the multifactorial physiology of reflux-like symptoms and develop an individualized plan for lifestyle changes that targets patients' specific symptom triggers (table 2 and table 3). (See 'Counseling and lifestyle changes' above.)

●Empiric treatment for most patients – For individuals with reflux-like symptoms who have not had an endoscopy, medical management of gastroesophageal reflux disease (GERD) is empiric and based on symptom frequency and severity (algorithm 1). (See 'Is upper endoscopy indicated?' above.)

•Patients with mild and intermittent symptoms – In patients with mild and intermittent (less than two episodes per week) reflux-like symptoms, we suggest initial treatment with as-needed low-dose histamine 2 receptor antagonists (H2RAs), antacids, and/or sodium alginates rather than continuous acid suppression with a proton pump inhibitor (PPI) (Grade 2C). This "step-up" approach minimizes medication overuse and controls symptoms in a significant proportion of individuals.

For patients with continued symptoms, we use standard-dose H2RAs or standard-dose PPIs once daily (table 4) (Grade 2B). (See 'Mild, intermittent symptoms' above.)

•Patients with frequent or severe symptoms – In patients with frequent (two or more episodes per week), severe symptoms, we suggest initial therapy with a standard-dose PPI once daily (Grade 2B). This maximizes the likelihood of rapid symptom relief. (See 'Severe or frequent symptoms' above.)

●Treatment based on endoscopy findings – In individuals who undergo early upper endoscopy, we base treatment on endoscopy results (algorithm 2).

•Patients with erosive esophagitis – In patients with erosive esophagitis (Los Angeles [LA] classification B to D), we recommend initial acid suppression therapy with vonoprazan 20 mg or a standard-dose PPI once daily (table 4) (Grade 1B). These medications demonstrate high rates of healing esophagitis and symptom improvement. We suggest vonoprazan over PPIs (Grade 2B) because it may heal esophagitis more rapidly and effectively, particularly in high-grade esophagitis (LA C to D). (See 'Patients with esophagitis' above.)

•Patients with Barrett's esophagus – Management of individuals with Barrett's esophagus and GERD is discussed separately. (See "Barrett's esophagus: Surveillance and management".)

•Other patients – We suggest standard-dose PPI therapy once daily for the initial treatment of patients without evidence of erosive esophagitis or Barrett's esophagus on endoscopy (Grade 2C). (See 'Patients without esophagitis or Barrett's esophagus' above.)

●Patients who respond to initial treatment

•Patients with high-grade esophagitis – Individuals with high-grade esophagitis (LA C to D) require long-term acid suppression with a PPI or potassium-competitive acid blocker (PCAB). Those with high-grade esophagitis should undergo repeat endoscopy to assess for Barrett's esophagus. (See 'Patients with high-grade esophagitis' above and "Barrett's esophagus: Surveillance and management".)

•Other patients – In patients on PPI or PCAB therapy who do not have high-grade esophagus or Barrett's esophagus, we continue acid suppression for eight weeks and then taper and/or stop the medications. Management of recurrent symptoms depends on the rapidity and severity of recurrence. (See 'Other patients' above.)

●Patients with persistent symptoms – Individuals whose symptoms do not resolve after initial PPI or PCAB therapy are considered to have refractory GERD or reflux-like symptoms. Their evaluation and management are discussed separately. (See "Approach to refractory gastroesophageal reflux disease in adults".)

●Patients who are pregnant or breastfeeding – Management of individuals who are pregnant or breastfeeding consists of lifestyle changes followed by pharmacologic therapy with antacids, alginates, or sucralfate. If symptoms persist, we use H2RAs and then PPIs. (See 'Patients who are pregnant or breastfeeding' above and 'Mild, intermittent symptoms' above.)