Dyspepsia

Dyspepsia (from the Greek "δυς-" (Dys-) and "πέψη" (Pepse)), popularly known as upset stomach or indigestion, meaning hard or difficult digestion, is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea or heartburn. Dyspepsia is a common problem, and is frequently due to gastroesophageal reflux disease (GERD) or gastritis, but in a small minority may be the first symptom of peptic ulcer disease (an ulcer of the stomach or duodenum) and occasionally cancer. Hence, unexplained newly-onset dyspepsia in people over 55 or the presence of other alarm symptoms may require further investigations.

Signs and symptoms
The characteristic symptoms of dyspepsia are upper abdominal pain, bloating, fullness and tenderness on palpation. Pain worsened by exertion and associated with nausea and perspiration may also indicate angina.

Occasionally dyspeptic symptoms are caused by medication, such as calcium antagonists (used for angina or high blood pressure), nitrates (used for angina), theophylline (used for chronic lung disease), bisphosphonates, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs, used as painkillers).

The presence of gastrointestinal bleeding (vomit containing blood), difficulty swallowing, anorexia (loss of appetite), unintentional weight loss, abdominal swelling and persistent vomiting are suggestive of peptic ulcer disease or malignancy, and would necessitate urgent investigations.

Diagnosis
People under 55 years, without alarm symptoms, can be treated without investigation. People over 55 years with recent onset dyspepsia or those with alarm symptoms should be urgently investigated by upper gastrointestinal endoscopy. This will rule out peptic ulcer disease, medication-related ulceration, malignancy and other rarer causes.

People under the age of 55 years with no alarm features do not need endoscopy but are considered for investigation for peptic ulcer disease caused by Helicobacter pylori infection. Investigation for H.pylori infection is usually performed when there is a moderate to high prevalence of this infection in the local community or the person with dyspepsia has other risk factors for H. pylori infection, related for example to ethnicity or immigration from a high-prevalence area. If infection is confirmed it can usually be eradicated by medication.

Medication-related dyspepsia is usually related to non-steroidal anti-inflammatory drugs (NSAIDs) and can be complicated by bleeding or ulceration with perforation of stomach wall.

Treatment
Functional and undifferentiated dyspepsia have similar treatments. Decisions around the use of drug therapy are difficult because trials included heartburn in the definition of dyspepsia. This led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn.

Traditional therapies used for this diagnosis include lifestyle modification, antacids, H2-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.

Antacids and sucralfate were found to be no better than placebo in a literature review. H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction ), but only a marginal benefit in good quality trials. Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia. They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride which has since been removed from the market (now only available as an investigational agent due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit. Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects.  Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride.  So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.

A 2004 meta-analysis, pooling data from three double-blind placebo-controlled studies, found the multiple herbal extract Iberogast to be significantly more effective than placebo (p value = .001) at treating patients with functional dyspepsia through the targeting of multiple dyspeptic pathologies. This German-made phytopharmaceutical was found to be equivalent to cisapride and significantly superior to metoclopramide at reducing the symptoms of functional dyspepsia over a four week period. Retrospective surveillance of 40,961 children (12 years and under) found no serious side-effects.

Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. There are, however, evidence-based guidelines and literature that evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006. The CADET study was the first to compare a PPI (omeprazole 20mg daily) to both an H2-RA (ranitidine 150mg BID) as well as a prokinetic agent (cisapride 20mg BID) alongside placebo. The study evaluated these agents in patients at 4 weeks and 6 months and noted that omeprazole had a significantly better response at 6 months (31%) than cisapride (13%) or placebo (14%) (p = .001) while it was just above the cutoff for being statistically significantly better than ranitidine (21%) (p = .053). Omeprazole also showed a significant increase in quality of life scores over the other agents and placebo in all but one category measured (p = .01 to .05).

The ENCORE study, which was a follow-up of patients from the OPERA study, showed responders to omeprazole therapy had fewer clinic visits than non-responders (1.5 vs 2.0) over a three month period (p < .001).