Management of Dyspepsia and GERD

First-Line Therapy

The American Gastroenterological Association recommends proton pump inhibitors (PPIs) as the first-line pharmacologic treatment for dyspepsia and GERD, with strong evidence for efficacy 1, 2, 3, 4.
PPIs should be used at the lowest dose that controls symptoms, as there is no apparent dose-response relationship 4, 5.
Optimize PPI timing, typically 30-60 minutes before the first meal, and consider escalation to twice-daily dosing if needed, or switch to a different PPI 1, 2.

The American College of Gastroenterology recommends testing all patients with dyspepsia for H. pylori using stool antigen test or carbon-urea breath test 6.
Eradication therapy is strongly recommended for H. pylori-positive patients, with high-quality evidence supporting efficacy 3, 4, 6.

The American Gastroenterological Association recommends personalizing adjunctive therapy to the specific GERD phenotype, rather than using empiric combinations 1, 2.
Alginate antacids, such as Gaviscon, are recommended for breakthrough symptoms, particularly post-prandial and nighttime symptoms 1, 2, 5, 7.
H2-receptor antagonists are recommended for nocturnal breakthrough symptoms, though effectiveness is limited by tachyphylaxis with chronic use 1, 2, 5.
Baclofen, a GABA-B agonist, is recommended for regurgitation-predominant or belch-predominant symptoms, though often limited by CNS and GI side effects 1, 2, 5, 7.

The American College of Gastroenterology recommends tricyclic antidepressants (TCAs) as neuromodulators as second-line treatment for refractory symptoms 3, 4.
Start with low-dose amitriptyline 10mg once daily, titrate slowly to maximum 30-50mg daily 3, 4.

Avoid opioids in patients with severe or refractory dyspepsia to minimize iatrogenic harm 3, 4, 6.
Do not use metoclopramide as monotherapy or adjunctive therapy for GERD 8.
Avoid empiric dose escalation without diagnostic confirmation, and perform upper endoscopy and consider pH monitoring if symptoms persist despite optimized PPI therapy 9.

The American Gastroenterological Association recommends aggressive lifestyle modifications, including weight management, regular aerobic exercise, avoiding specific food triggers, and elevating the head of bed for nocturnal symptoms 1, 2, 6, 9.
Caution against overly restrictive diets that could lead to nutritional deficiencies 6.

The American Gastroenterological Association (AGA) recommends that prokinetics should be personalized to the GERD phenotype rather than used empirically, and are specifically indicated only for coexistent gastroparesis—not for routine GERD management 10, 11, 12
Prokinetic therapy for GERD involves medications that enhance gastrointestinal motility by increasing lower esophageal sphincter pressure, accelerating gastric emptying, and improving esophageal peristalsis—but should only be used in highly selected patients with coexistent gastroparesis, not as routine adjunctive therapy for typical GERD 10, 11

The AGA guidelines explicitly state that prokinetics are reserved for patients with proven gastroparesis in addition to GERD 10, 11
Prokinetics may be considered for regurgitation-predominant symptoms, though baclofen (a GABA-B agonist) is preferred over traditional prokinetics for this indication 10, 11, 12

The American College of Chest Physicians (ACCP) 2006 guidelines suggested adding prokinetic therapy (specifically metoclopramide) if there was no or little response to PPI and lifestyle modifications 13, 14, 15
The 2022 AGA guidelines represent a paradigm shift away from empiric prokinetic use 10, 11, 12

For patients with GERD symptoms not responding to PPI therapy, the AGA recommends optimizing PPI dosing and adding phenotype-specific adjunctive therapy, considering prokinetic therapy only if gastroparesis is documented 10, 11, 12
The treatment algorithm includes adding alginate antacids for breakthrough symptoms, H2-receptor antagonists for nocturnal symptoms, and baclofen for regurgitation or belch-predominant symptoms 10, 11, 12