A. Symptoms and Signs

Given the nonspecific nature of dyspeptic symptoms, the history has limited diagnostic utility. It should clarify the chronicity, location, and quality of the epigastric pain, and its relationship to meals. Concomitant weight loss, persistent vomiting, constant or severe pain, progressive dysphagia, hematemesis, melena, or unexplained iron deficiency anemia warrants upper endoscopy or abdominal CT imaging. Potentially offending medications and excessive alcohol use should be identified and discontinued if possible. The patient should be asked about a family history of upper GI cancer. The patient's reason for seeking care should be determined. Recent changes in employment, marital discord, physical and sexual abuse, anxiety, depression, and fear of serious disease may all contribute to the development and reporting of symptoms. Patients with functional dyspepsia often are younger, report a variety of abdominal and extragastrointestinal complaints, show signs of anxiety or depression, or have used psychotropic medications.

The symptom profile alone does not differentiate between functional dyspepsia and organic GI disorders. Based on the clinical history alone, primary care clinicians misdiagnose nearly half of patients with peptic ulcers or gastroesophageal reflux.

The physical examination is rarely helpful. Signs of serious organic disease such as weight loss, organomegaly, abdominal mass, or fecal occult blood must be further evaluated.

B. Laboratory Findings

In patients younger than age 60 with uncomplicated dyspepsia (in whom gastric cancer is rare), a noninvasive test for H pylori (urea breath test, fecal antigen test) should be performed first-both of which have 95% accuracy. Serologic tests for H pylori antibodies are not recommended due to their poor performance characteristics. If H pylori breath test or fecal antigen test results are negative in a patient not taking NSAIDs, peptic ulcer disease is virtually excluded. In patients older than age 60 years, initial laboratory work should include a CBC, serum electrolytes, liver enzymes, calcium, and thyroid function tests but the cost-effectiveness of such studies is uncertain.

C. Upper Endoscopy

Upper endoscopy is mainly indicated to look for upper gastric or esophageal malignancy in all patients over age 60 years with new-onset dyspepsia (in whom there is increased malignancy risk). In patients under age 60, the risk of malignancy is less than 1% so recent guidelines recommend against routine endoscopy for most younger patients-except those with prominent “alarm” features, such as progressive weight loss, progressive dysphagia, persistent vomiting, evidence of bleeding or iron deficiency anemia, palpable abdominal mass, or a family history of upper GI cancer. Upper endoscopy 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.

Endoscopy may also be warranted when symptoms fail to respond to initial empiric management or when frequent symptom relapse occurs after discontinuation of empiric therapy.

D. Other Tests

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) 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.

A. Empiric Therapy

Patients younger than age 60 should be tested for H pylori and, if positive, treated with an effective regimen (see Table 17-10). H pylori eradication 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.

H pylori-negative patients and patients with persistent dyspepsia after H pylori eradication most likely have functional dyspepsia or atypical GERD and should be treated with a PPI for 4 weeks. Meta-analysis of six RCTs reported symptom improvement in 50% of patients treated with a PPI versus 27% of those treated with a placebo. For patients who have symptom relapse after discontinuation of the PPI, intermittent or long-term PPI therapy may be considered.

B. 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 PPI therapy are presumed to have functional dyspepsia. Patients with mild, intermittent symptoms may respond to reassurance and lifestyle or dietary changes. A food diary, in which patients record their food intake, symptoms, and daily events, may reveal dietary or psychosocial precipitants of pain. Herbal therapies (peppermint, caraway) may offer benefit with little risk of adverse effects. In a 2022 RCT, cannabidiol (CBD) was not more effective than placebo in relief of functional dyspepsia.

Antisecretory drugs (PPIs or H₂-receptor antagonists) have demonstrated limited efficacy in the treatment of functional dyspepsia. A small number of patients (less than 10%) derive benefit from H pylori eradication therapy. Low doses of tricyclic antidepressants (eg, desipramine or nortriptyline, 25-50 mg orally at bedtime) benefit some patients, possibly by moderating visceral afferent sensitivity. Doses should be increased slowly to minimize side effects. SSRIs do not appear to be beneficial. Although some prokinetics have demonstrated modest improvement in global symptoms compared to placebo in controlled trials, the more effective agents are either not available in the United States (domperidone) or were removed from the market to due rare but serious adverse events (cisapride). Metoclopramide (5-10 mg three times daily) may improve symptoms but cannot be recommended for long-term use due to the risk of tardive dyskinesia. Prucalopride is a highly selective serotonin 5-HT₄-receptor agonist (2 mg orally each day) that has demonstrated improvement in gastric emptying and symptoms in patients with gastroparesis; however, its efficacy in functional dyspepsia has not been studied. Psychological therapies may also be used in patients with depression and anxiety.