Dyspepsia refers to acute, chronic, or recurrent pain or discomfort centered in the upper abdomen. A 2017 American College of Gastroenterology guideline has further defined clinically relevant dyspepsia as predominant epigastric pain for at least 1 month. The epigastric pain may be associated with other symptoms of heartburn, nausea, fullness, or vomiting. Heartburn (retrosternal burning) should be distinguished from dyspepsia. When heartburn is the dominant complaint, gastroesophageal reflux is nearly always present. Dyspepsia occurs in 7% of the adult population and accounts for 3% of general medical office visits.
Food or Drug Intolerance
Acute, self-limited “indigestion” may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), dabigatran, diabetes drugs (metformin, alpha-glucosidase inhibitors, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors, angiotensin-receptor blockers), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (dopamine agonists, monoamine oxidase [MAO]-B inhibitors), corticosteroids, estrogens, digoxin, iron, and opioids.
Functional dyspepsia refers to dyspepsia for which no organic etiology has been determined by endoscopy or other testing. This is the most common cause of chronic dyspepsia, accounting for the majority of patients. Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying or impaired accommodation to food, or psychosocial stressors. Although benign, these symptoms may be chronic and difficult to treat.
Luminal Gastrointestinal Tract Dysfunction
Peptic ulcer disease is present in 5–15% of patients with dyspepsia. Gastroesophageal reflux disease (GERD) is present in up to 20% of patients with dyspepsia, even without significant heartburn. Gastric or esophageal cancer is identified in less than 1% but is extremely rare in persons under age 60 years with uncomplicated dyspepsia. Other causes include gastroparesis (especially in diabetes mellitus) and parasitic infection (Giardia, Strongyloides, Anisakis).
Helicobacter pylori Infection
Chronic gastric infection with H pylori is an important cause of peptic ulcer disease, and may cause dyspepsia in a small number of patients in the absence of peptic ulcer disease.
Pancreatic carcinoma and chronic pancreatitis may cause chronic epigastric pain that is more severe, sometimes radiates to the back, and usually is associated with anorexia, rapid weight loss, steatorrhea, or jaundice.
Biliary Tract Disease
The abrupt onset of epigastric or right upper quadrant pain due to cholelithiasis or choledocholithiasis should be readily distinguished from dyspepsia.
Diabetes mellitus, thyroid disease, chronic kidney disease, myocardial ischemia, intra-abdominal malignancy, gastric volvulus or paraesophageal hernia, chronic gastric or intestinal ischemia, and pregnancy are sometimes accompanied by acute or chronic epigastric pain or discomfort.
In patients younger than age 60 with uncomplicated dyspepsia (in whom gastric cancer is rare), initial noninvasive strategies should be pursued. In patients older than age 60 years, initial laboratory work should include a blood count, electrolytes, liver enzymes, calcium, and thyroid function tests. The cost-effectiveness of routine laboratory studies is uncertain. In most patients younger than age 60, a noninvasive test for H pylori (urea breath test, fecal antigen test) should be performed first. Although serologic tests are inexpensive, performance characteristics are poor in low-prevalence populations, whereas breath and fecal antigen tests have 95% accuracy. If H pylori breath test or fecal antigen test results are negative in a patient not taking NSAIDs, peptic ulcer disease is virtually excluded.
Upper endoscopy is the study of choice to diagnose gastroduodenal ulcers, erosive esophagitis, and upper gastrointestinal malignancy. However, gastroduodenal ulcers and erosive esophagitis can be treated empirically with H pylori eradication or empiric proton pump inhibitor therapy or both. Therefore, upper endoscopy is mainly indicated to look for upper gastric or esophageal malignancy in patients over age 60 years with new-onset dyspepsia (in whom there is increased malignancy risk) and in selected younger patients with “alarm” features. In patients under age 60, the risk of malignancy is less than 1%—even among patients with reported “alarm” features.
Recent guidelines therefore recommend against routine endoscopy for younger patients—even those with “alarm” features. However, endoscopy should be performed in patients with prominent “alarm” features, such as progressive weight loss, rapidly progressive dysphagia, severe vomiting, evidence of bleeding or anemia, or jaundice. It is also helpful for selected patients who are excessively concerned about serious underlying disease.
For patients born in regions in which there is a higher incidence of gastric cancer, such as Central or South America, China and Southeast Asia, or Africa, an age threshold of 45 years may be more appropriate.
Endoscopic evaluation may also be warranted when symptoms fail to respond to initial empiric management strategies or when frequent symptom relapse occurs after discontinuation of empiric therapy.
In patients with refractory symptoms or progressive weight loss, antibodies for celiac disease or stool testing for ova and parasites or Giardia antigen, fat, or elastase may be considered. Abdominal imaging (ultrasonography or CT scanning) is performed only when pancreatic, biliary tract, vascular disease, or volvulus is suspected. Gastric emptying studies may be useful in patients with recurrent nausea and vomiting who have not responded to empiric therapies.
Initial empiric treatment is warranted for patients who are younger than age 60 years and who lack severe or worrisome “alarm” features. All other patients as well as patients whose symptoms do not to respond to or relapse after empiric treatment should undergo upper endoscopy with subsequent treatment directed at the specific disorder identified (eg, peptic ulcer, gastroesophageal reflux, cancer). When endoscopy is performed, gastric biopsies should be obtained to test for H pylori infection. If infection is present, antibacterial treatment should be given.
H pylori–negative patients most likely have functional dyspepsia or atypical GERD and can be treated with an antisecretory agent (proton pump inhibitor) for 4 weeks. For patients who have symptom relapse after discontinuation of the proton pump inhibitor, intermittent or long-term proton pump inhibitor therapy may be considered. For patients in whom test results are positive for H pylori, antibiotic therapy proves definitive for patients with underlying peptic ulcers and may improve symptoms in a small subset (less than 10%) of infected patients with functional dyspepsia. Patients with persistent dyspepsia after H pylori eradication can be given a trial of proton pump inhibitor therapy.
Treatment of Functional Dyspepsia
Patients who have no significant findings on endoscopy as well as patients under age 60 who do not respond to H pylori eradication or empiric proton pump inhibitor therapy are presumed to have functional dyspepsia.
Most patients have mild, intermittent symptoms that respond to reassurance and lifestyle changes. Alcohol and caffeine should be reduced or discontinued. Patients with postprandial symptoms should be instructed to consume small, low-fat meals. A food diary, in which patients record their food intake, symptoms, and daily events, may reveal dietary or psychosocial precipitants of pain.
Anti–H pylori treatment
Meta-analyses have suggested that a small number of patients with functional dyspepsia (less than 10%) derive benefit from H pylori eradication therapy. Therefore, patients with functional dyspepsia should be tested and treated for H pylori.
Other pharmacologic agents
Drugs have demonstrated limited efficacy in the treatment of functional dyspepsia. One-third of patients derive relief from placebo. Antisecretory therapy for 4–8 weeks with proton pump inhibitors (omeprazole, esomeprazole, or rabeprazole 20 mg, dexlansoprazole or lansoprazole 30 mg, or pantoprazole 40 mg orally daily) may benefit up to 10% of patients.
Low doses of antidepressants (eg, desipramine or nortriptyline, 25–50 mg orally at bedtime) benefit some patients, possibly by moderating visceral afferent sensitivity. A 2015 multicenter controlled trial reported adequate symptom improvement in 53% of patients treated with amitriptyline (50 mg/day) at 10 weeks compared with placebo (40%) and escitalopram (38%), particularly those with upper abdominal pain (ulcer-like dyspepsia). Doses should be increased slowly to minimize side effects. Metoclopramide (5–10 mg three times daily) may improve symptoms, but improvement does not correlate with the presence or absence of gastric emptying delay.
In 2009, the FDA issued a black box warning that metoclopramide use for more than 3 months is associated with a high incidence of tardive dyskinesia and should be avoided. Older adults, particularly elderly women, are most at risk.
Psychotherapy and hypnotherapy may be of benefit in selected motivated patients with functional dyspepsia. Herbal therapies (peppermint, caraway) may offer benefit with little risk of adverse effects.