|Classification and external resources|
Dyspepsia (from the Greek δυσ- dys-, "bad" or "difficult", and πέψις pepsis "digestion"), also known as indigestion, is a condition of impaired digestion. It 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 caused by gastroesophageal reflux disease (GERD) or gastritis. In a small minority it 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 alarming symptoms may require further investigations.
Functional dyspepsia (previously called nonulcer dyspepsia) is dyspepsia "without evidence of an organic disease that is likely to explain the symptoms". Functional dyspepsia is estimated to affect about 15% of the general population in western countries.
Signs and symptoms
In most cases, the clinical history is of limited use in distinguishing between organic causes from functional dyspepsia. A large systematic review of the literature was recently performed to evaluate the effectiveness of diagnosing organic dyspepsia by clinical opinion versus computer models in patients referred for upper endoscopy. The computer models were based on patient demographics, risk factors, historical items,and symptoms. The study showed that neither clinical impression nor computer models were able to adequately distinguish organic from functional disease.
In a recent study, patients with peptic ulcer disease were compared with patients with functional dyspepsia in an age and sex-matched study. Although the functional dyspepsia group reported more upper abdominal fullness, nausea, and overall greater distress and anxiety, almost all the same symptoms were seen in both groups. Therefore, it is the clinician’s challenging task to separate patients who may have an organic disorder, and thus warrant further diagnostic testing, from patients who have functional dyspepsia, who are given empiric symptomatic treatment.The workup should be targeted to identify or rule out specific causes. Traditionally, high-risk patients have been identified by “alarm” features. However, the utility of these features in identifying the presence of upper gastrointestinal malignancy has been debated.A recent meta analysis looking at the sensitivity and specificity of alarm features found a range of 0–80% and 40–98%, respectively. However, there was high heterogeneity between studies.
The physical examination may elicit abdominal tenderness, but this finding is nonspecific. A positive Carnett sign, or focal tenderness that increases with abdominal wall contraction and palpation, suggests an etiology involving the abdominal wall musculature. Cutaneous dermatomal distribution of pain may suggest a thoracic polyradiculopathy. Thump tenderness over the right upper quadrant may suggest chronic cholecystitis. 
In about 50-70% of patients with dyspepsia, no definite organic cause can be determined. In this case, dyspepsia is referred to as non-ulcer dyspepsia and its diagnosis is established by the presence of epigastralgia for at least 6 months, in the absence of any other cause explaining the symptoms.
Functional Dyspepsia This is the most common cause of chronic dyspepsia. Up to three-fourths of patients have no obvious organic cause for their symptoms after evaluation. 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.
Diseases of the gastrointestinal tract
When dyspepsia can be attributed to a specific cause, the majority of cases concern gastroesophageal reflux disease (GERD) and peptic ulcer disease. Less common causes include gastritis, gastric cancer, esophageal cancer, coeliac disease, food allergy, inflammatory bowel disease, chronic intestinal ischemia and gastroparesis.
Liver and pancreas diseases
Food or Drug Intolerance
Acute, self-limited dyspepsia 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), diabetes drugs (metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), corticosteroids, estrogens, digoxin, iron, and opioids. 
Helicobacter pylori Infection
The role of H. pylori in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between H. pylori infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status. Controlled trials disagree about whether or not H. pylori eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement.In a recent multicenter U.S.trial that randomized 240 patients to treatment or placebo, and followed patients for 12 months, 28% of treated patients versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after H pylori eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results.A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89;P= 0.18).Still,no effect was seen after adjusting for heterogeneity and for cure of H. pylori. In contrast, the most recent update of a Cochrane Database review showed a small but statistically significant effect in curing symptoms (H pylori cure vs placebo, 36% vs 30%, respectively; relative risk reduction [RRR],8% [95% CI,3–18%],number needed to treat [NNT] = 18]).
There is a number of systemic diseases that may involve dyspepsia and include coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, chronic renal disease and adrenal fatigue.
Psychosomatic and cognitive factors are important in the evaluation of patients with chronic dyspepsia. The psychiatric hypothesis holds that the symptoms of dyspepsia maybe due to depression,increased anxiety,or a somatization disorder. Epidemiologic studies suggest there is an association between functional dyspepsia and psychological disorders. Symptoms of neurosis, anxiety, hypochondriasis, and depression are more common in patients being evaluated for unexplained gastrointestinal complaints than in healthy controls.Comparisons of functional and organic dyspepsia have demonstrated that patients with functional dyspepsia are less likely to have decreased stress or anxiety at 1-year follow-up after being reassured of having no serious disease. This suggests that functional dyspepsia symptoms are long-lasting, compared with those of organic dyspepsia,and that the emotional ties are strong.
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 NSAIDs and can be complicated by bleeding or ulceration with perforation of stomach wall.
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.
Pharmacological acid suppression
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 2002 systemic review of herbal products found that several herbs, including peppermint and caraway, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles". 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. Red pepper powder has also found to be promising. Ginger and related products made therefrom have been shown to have some positive alleviation of symptoms, in particular for motion sickness and pregnancy-related nausea 
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 20 mg daily) to both an H2-RA (ranitidine 150 mg BID) as well as a prokinetic agent (cisapride 20 mg 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).
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