Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

initial presentation

1st line – standard-dose or high-dose proton-pump inhibitor

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ACUTE
|
initial presentation
|
non-pregnant
1st line – 

standard-dose or high-dose proton-pump inhibitor

Provides rapid symptom relief and healing in oesophagitis (>80% of patients).[122]

For patients who present with typical, regular heartburn and no alarm symptoms, treatment should be started with standard-dose proton-pump inhibitors (PPIs) for about 8 weeks in combination with lifestyle changes.[1][36]​​ In the UK, the National Institute for Health and Care Excellence recommends initial PPI treatment for 4 or 8 weeks.[36]

Patients who have extra-oesophageal features (e.g., laryngitis, globus, tooth enamel erosion, halitosis) with typical GORD symptoms may have an initial 8 to 12 week trial of high-dose PPI therapy before endoscopy or further testing.[1][6]

It is recommended to start treatment with the lowest effective dose of PPI.[1][5][69]​​​​ After achieving adequate symptom control, the PPI should be tapered to the lowest effective dose.[37] Most patients will need ongoing therapy.

PPIs reduce gastric pH most effectively when taken 30 to 60 minutes before meals.[1][5]

Primary options

Standard-dose PPI

omeprazole: 20 mg orally once daily

OR

Standard-dose PPI

omeprazole/sodium bicarbonate: 20 mg orally once daily

More

OR

Standard-dose PPI

esomeprazole: 20 mg orally once daily

OR

Standard-dose PPI

rabeprazole: 20 mg orally once daily

OR

Standard-dose PPI

pantoprazole: 40 mg orally once daily

OR

Standard-dose PPI

lansoprazole: 15 mg orally once daily

OR

Standard-dose PPI

dexlansoprazole: 30 mg orally once daily

Secondary options

High-dose PPI

omeprazole: 40 mg orally twice daily

More

OR

High-dose PPI

esomeprazole: 40 mg orally twice daily

More

OR

High-dose PPI

rabeprazole: 20 mg orally twice daily

More

OR

High-dose PPI

pantoprazole: 40 mg orally twice daily

More

OR

lansoprazole: 30 mg orally twice daily

More

OR

High-dose PPI

dexlansoprazole: 60 mg orally once daily

More

Plus – diet and lifestyle modification

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ACUTE
|
initial presentation
|
non-pregnant
Plus – 

diet and lifestyle modification

Treatment recommended for ALL patients in selected patient group

Recommended for all patients.[1] Measures include: weight loss for overweight people; smoking cessation for tobacco smokers; head-of-bed-elevation; and avoidance of late-night eating if nocturnal symptoms are present.[1][67]

Patients should avoid eating 3 hours before bedtime and sleeping on the right side.[5]​ Four to five small meals are preferred over two or three large meals.[5]

Specific food eliminations (e.g., chocolate, caffeine, alcohol, acidic and/or spicy foods) are not required unless selective changes provide individual benefit.[1]

One randomised controlled trial found that reducing the intake of simple sugars improved pH monitoring outcomes and GORD symptoms.[68]

1st line – diet and lifestyle modification

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ACUTE
|
initial presentation
|
pregnant: mild symptoms
1st line – 

diet and lifestyle modification

Modification of diet and lifestyle is key for the treatment of GORD symptoms in pregnancy.[12][99]​​​ Mild GORD symptoms can usually be managed with changes in diet and lifestyle alone. Smaller and frequent meals are recommended. Late-night meals and laying down within 3 hours of meals should be avoided. Consumption of meats, carbonated beverages, fatty foods, and spicy foods should be minimised or avoided to prevent reflux.[12]

1st line – antacid or alginate or sucralfate

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ACUTE
|
initial presentation
|
pregnant: moderate symptoms
1st line – 

antacid or alginate or sucralfate

Antacids, alginates, and sucralfate are the preferred first-line options.

Antacids containing sodium bicarbonate may cause maternal or fetal metabolic alkalosis and fluid overload and should be avoided.[13]

Magnesium-containing and calcium-containing antacids can be safely used in lactating mothers as magnesium and calcium salts are poorly absorbed orally; as a result, their blood levels are negligible and only traces may be found in milk, making them a safe alternative.[12]​ Antacids should be avoided within 2 hours of iron and folic acid supplements, as gastric acid is required for the absorption of these supplements.​[13][99]

Combination of an alginate plus an antacid is shown to reduce post-prandial acid reflux.[99][100][101]​ Owing to limited maternal absorption, alginates are usually considered safe during lactation.[99]

Sucralfate is used to treat gastric ulcers and exerts its mucosal protection through a local effect.[12]​ Sucralfate has been found to be effective in reducing heartburn and regurgitation symptoms. Based on human and animal studies, it is considered a safe first-line option to treat GORD during pregnancy.[12][13]​​

Various antacids and alginates are available over the counter.

Primary options

sucralfate: short-term treatment: 1 g orally four times daily; maintenance treatment: 1 g orally twice daily

Plus – diet and lifestyle modification

Back
ACUTE
|
initial presentation
|
pregnant: moderate symptoms
Plus – 

diet and lifestyle modification

Treatment recommended for ALL patients in selected patient group

Smaller and frequent meals are recommended. Late-night meals and laying down within 3 hours of meals should be avoided. Consumption of meats, carbonated beverages, fatty foods, and spicy foods should be minimised or avoided to prevent reflux.[12][99]

2nd line – H2 antagonist

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ACUTE
|
initial presentation
|
pregnant: moderate symptoms
2nd line – 

H2 antagonist

If symptoms persist, H2 antagonists are recommended. Famotidine is the preferred H2 antagonist during breastfeeding as least excretion into milk has been reported. Cimetidine has the greatest excretion into milk, but no adverse effects in infants are reported.[12]

Primary options

famotidine: 20 mg orally twice daily

OR

cimetidine: 800 mg orally twice daily; or 400 mg orally four times daily

Plus – diet and lifestyle modification

Back
ACUTE
|
initial presentation
|
pregnant: moderate symptoms
Plus – 

diet and lifestyle modification

Treatment recommended for ALL patients in selected patient group

Smaller and frequent meals are recommended. Late-night meals and laying down within 3 hours of meals should be avoided. Consumption of meats, carbonated beverages, fatty foods, and spicy foods should be minimised or avoided to prevent reflux.[12][99]

ONGOING

non-pregnant: proton-pump inhibitor-responsive

1st line – continued standard-dose proton-pump inhibitor

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ONGOING
|
non-pregnant: proton-pump inhibitor-responsive
1st line – 

continued standard-dose proton-pump inhibitor

Patients who respond to therapy will often need long-term maintenance treatment.

Maintenance PPI therapy is recommended for those who have symptoms when the PPI is discontinued, and for those with erosive oesophagitis and Barrett's oesophagus.[1]

Some people with non-erosive reflux disease (NERD) may be able to use on-demand or intermittent PPI therapy.[1] [ Cochrane Clinical Answers logo ] ​ Some experts recommend a trial of step-down therapy, although it is not routine.​[71]​​[72]

Lifestyle changes can be continued, if they appear to be effective.[1]

Several studies have highlighted the risks associated with long-term use of PPIs; therefore, attempts to stop or reduce the dose to the minimum necessary to maintain symptomatic control should always be pursued.[64][65][Evidence C]

Concomitant use of clopidogrel and omeprazole is not recommended.

Primary options

omeprazole: 20 mg orally once daily

OR

omeprazole/sodium bicarbonate: 20 mg orally once daily

More

OR

esomeprazole: 20 mg orally once daily

OR

rabeprazole: 20 mg orally once daily

OR

pantoprazole: 40 mg orally once daily

OR

lansoprazole: 15 mg orally once daily

OR

dexlansoprazole: 30 mg orally once daily

2nd line – surgery

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ONGOING
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non-pregnant: proton-pump inhibitor-responsive
2nd line – 

surgery

Surgery (e.g., open fundoplication, laparoscopic fundoplication, magnetic sphincter augmentation) is reserved mainly for people who have had a good response to PPIs, but who are non-adherent to therapy or do not wish to take long-term medical treatment (e.g., due to adverse effects).[1] People who do not respond to PPIs pre-operatively are less likely to respond to surgery.[1]

Only a very small percentage of the GORD patient population undergoes anti-reflux surgery each year.[72][73]​ All patients should be involved in the decision to initiate anti-reflux surgery. Post-surgical complications occur in up to 20% of patients.[75]

US and European guidelines suggest that the choice of anti-reflux surgery procedure should be informed by surgical expertise and regional practice.[76][77][78]​​

Guidelines recommend preoperative ambulatory pH monitoring if no evidence of erosive oesophagitis, and preoperative manometry.[1][77][78]​​

Meta-analyses of randomised controlled trials indicate that, in the short-term, GORD-related quality of life outcomes may be superior following surgery than medical treatment.[79][80]

Laparoscopic surgery appeared to be more effective than PPIs for improving heartburn and reflux in the short (<1 year) and medium (1-5 years) term; rates of dysphagia in the short and medium term were greater among people who underwent surgery.[79] [ Cochrane Clinical Answers logo ] ​Studies included in these meta-analyses had important methodological limitations.[79][80]

In one meta-analysis of 12 randomised clinical trials, laparoscopic anti-reflux surgery was associated with a significant reduction in duration of hospital stay, return to normal activity, and complication rates, compared with open anti-reflux surgery.[81] Operative time was longer, and need for further surgery higher, in the laparoscopic group. Findings from the meta-analysis are limited by poor-quality data, variation across trials, and publication bias.

A subsequent meta-analysis reported similar results.[82]

Long-term effectiveness of surgery is unclear; the benefits must be balanced against the risk of mortality and other adverse effects.​[79][83] [ Cochrane Clinical Answers logo ] [Evidence C]​​ 

In one large retrospective cohort study, in which 2,655 individuals were followed for a median of 5.6 years following laparoscopic anti-reflux surgery, reflux recurrence (defined as need for acid suppressants for >6 months or repeat anti-reflux surgery) was reported in 17.7% of individuals.[84] Risk factors for reflux recurrence included: female sex, older age, and presence of comorbid conditions.[84]

Network meta-analysis of more than 50 randomised controlled trials indicates that posterior partial fundoplication may be the preferred surgical approach for management of GORD in adults.[85] ​

Findings were consistent across all follow‐up time points (including medium- [1-5 years] and long‐term [≥10 years]).[85]

Obesity is associated with an increased risk for recurrence of GORD symptoms in patients undergoing laparoscopic anti-reflux surgery.[86][87] ​​Mean operative times are greater for obese patients.[86][88]

Obese patients considering anti-reflux surgery may be candidates for bariatric surgery.[1]

2nd line – transoral incisionless fundoplication

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ONGOING
|
non-pregnant: proton-pump inhibitor-responsive
2nd line – 

transoral incisionless fundoplication

Transoral incisionless fundoplication (TIF) is an entirely endoscopic procedure to reconstruct the gastro-oesophageal valve and help restore an anatomical reflux barrier. In a systematic review and network meta-analysis, short-term likelihood of increased quality of life was greater following TIF than laparoscopic Nissen fundoplication (LNF).[89] LNF was, however, found to have the greatest ability to improve physiologic parameters of GORD. The long-term efficacy of TIF remains to be determined.[90][91]

Candidates for TIF must be carefully selected. In general, a hiatus hernia of >2 cm is considered a contraindication, unless TIF is performed simultaneously with laparoscopic hernia repair.

non-pregnant: incomplete response to proton-pump inhibitor

1st line – high-dose proton-pump inhibitor + further testing

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ONGOING
|
non-pregnant: incomplete response to proton-pump inhibitor
1st line – 

high-dose proton-pump inhibitor + further testing

If there is absent or inadequate response, treatment can proceed to high-dose PPI and endoscopy.[1] If it is not possible to use a high-dose PPI, some patients respond to switching the PPI. More than one switch of PPI is not recommended.[63]

If endoscopy fails to show erosive oesophagitis or Barrett oesophagus, further diagnostic testing should be considered. Patients with refractory GORD should be referred to a gastroenterologist for diagnostic testing.

Reasons for lack of response to therapy should be sought. These may include: functional GORD/hypersensitivity (patient does not have GORD by standard pH definition); non-adherence to treatment; non-acid reflux; inadequate acid control; Zollinger-Ellison syndrome, or individuals with polymorphisms in cytochrome P450 2C19 (CYP2C19) resulting in rapid metabolism of proton pump inhibitors.[70]

There are risks associated with long-term use of PPIs; therefore, attempts to stop or reduce the dose to the minimum necessary to maintain symptomatic control should always be pursued.[64][65]

Concomitant use of clopidogrel and omeprazole is not recommended.

Primary options

omeprazole: 40 mg orally twice daily

OR

esomeprazole: 40 mg orally twice daily

OR

rabeprazole: 20 mg orally twice daily

OR

pantoprazole: 40 mg orally twice daily

OR

lansoprazole: 30 mg orally twice daily

OR

dexlansoprazole: 60 mg orally once daily

Consider – H2 antagonist

Back
ONGOING
|
non-pregnant: incomplete response to proton-pump inhibitor
|
with nocturnal component
Consider – 

H2 antagonist

Additional treatment recommended for SOME patients in selected patient group

When proton-pump inhibitors (PPIs) are not completely effective, bedtime adjunctive use of an H2 antagonist may be considered in people with nocturnal symptoms or with pH-monitoring evidence of nocturnal oesophageal acid reflux.[1]​​[37]​ However, tachyphylaxis may occur, and few data guide dose. As-needed dosing may be possible.[1]

Primary options

famotidine: consult specialist for guidance on dose

OR

nizatidine: consult specialist for guidance on dose

OR

cimetidine: consult specialist for guidance on dose

pregnant: intractable symptoms or complicated reflux disease

1st line – proton-pump inhibitor

Back
ONGOING
|
pregnant: intractable symptoms or complicated reflux disease
1st line – 

proton-pump inhibitor

PPIs are generally considered safe during pregnancy, based on real-world evidence.[12]​ However, several studies have highlighted risks associated with long-term use of PPIs.[64][65][103][Evidence C]​ Thus, the use of PPIs should be restricted to women with intractable symptoms or complicated reflux disease.[13][102]​ Omeprazole should be avoided in both pregnancy and lactation.[99]

Consult a specialist for guidance on the choice of PPIs during pregnancy.

Additional testing (upper GI endoscopy, esophageal manometry, and reflux testing) may be necessary in case of persistent GORD symptoms.

Plus – diet and lifestyle modification

Back
ONGOING
|
pregnant: intractable symptoms or complicated reflux disease
Plus – 

diet and lifestyle modification

Treatment recommended for ALL patients in selected patient group

Smaller and frequent meals are recommended. Late-night meals and laying down within 3 hours of meals should be avoided. Consumption of meats, carbonated beverages, fatty foods, and spicy foods should be minimised or avoided to prevent reflux.[12][99]​​

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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