Dyspepsia

Dyspepsia (from the Greek "δυς-" (Dys-), meaning hard or difficult, and "πέψη" (Pepse), meaning digestion) is chronic or recurrent pain or discomfort centered in the upper abdomen ^[1] Discomfort, in this context, includes mild pain, upper abdominal fullness and feeling full earlier than expected with eating. It can be accompanied by bloating, belching, nausea or heartburn. Heartburn is excluded from the definition of dyspepsia in ICD 10, as it usually has a different cause and management pathway.

Many people get dyspepsia. It is often caused by lifestyle factors, such as smoking and diet, but there are some serious causes such as cancer of the stomach, peptic ulcer disease and some medications. When people have dyspepsia but no risk factors for any of the serious causes, it can be labeled undifferentiated dyspepsia and treated without further investigations. When people have been investigated for dyspepsia but no cause has been found it can be labeled as functional dyspepsia.

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Investigation of dyspepsia

People without risk factors for serious causes of dyspepsia usually do not need investigation beyond an office based clinical examination. However, people over the age 55 years and those with alarm features are usually investigated by esophagogastroduodenoscopy (EGD or OGD in Britain). In this painless investigation the esophagus, stomach and duodenum are examined through an endoscope passed down through the mouth. 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 EGD 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 of Functional Dyspepsia and Undifferentiated Dyspepsia

Treatment safely and successfully prescribed by doctors in Pakistan is a 10 day course and includes the following:
(1)Risek 20mg capsules 1+1 for 10 days
(2)Amoxil 500mg capsules 2+2 for 10 days
(3)Claritek 500mg tablets 1+1 for 10 days
(4)Ulsanic syrup 2+2+2 for 10 days
^{[citation needed]}

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 questionably 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 is 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^[2].

Antacids and sucralfate were found to be no better than placebo in a literature review^[3]. H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction^[3]), but only a marginal benefit in good quality trials^[2]. Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia^[2]. 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^[4]) due to serious adverse events such as torsades¬, and publication bias has been cited as a potential partial explanation for such a high benefit^[3]. Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects^[3]. Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride^[3]. 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 = 0.001) at treating patients with functional dyspepsia through the targeting of multiple dyspeptic pathologies^[5]. This German-made phytopharmaceutical was found to be equivalent to cisapride and significantly superior to metochlopramide at reducing the symptoms of functional dyspepsia over a four week period.^[6][7] Retrospective surveillance of 40,961 children (12 years and under) found no serious side-effects^[8].

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^[2].

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^[9]. 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 = 0.001) while it was just above the cutoff for being statistically significantly better than ranitidine (21%) (p = 0.053). Omeprazole also showed a significant increase in quality of life scores over the other agents and placebo in all but one category measured (p = 0.01 to 0.05).

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 < 0.001)^[10][11].

References

1. ^ N. Talley, et al., "Guidelines for the management of dyspepsia", American Journal of Gastroenterology 100 (2005), pp. 2324-2337.
2. ^ ^{a b c d} Monkemuller K, Malfertheiner P. Drug treatment of functional dyspepsia. World J Gastroenterol. 2006 May 7;12(17):2694-700.
3. ^ ^{a b c d e}
4. ^ Anonymous. Information regarding withdrawal of Propulsid (cisapride) by Janssen Pharmaceutica. From FDA website (http://www.fda.gov/medwatch/safety/2000/safety00.htm#propul).
5. ^ Melzer J, Rosch W, Reichling J, Brignoli R, Saller R (2004). "Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW-5 (Iberogast)". Aliment Pharmacol Ther 20: 1279–87.
6. ^ Rosch w, Vinson B, Sassin, I (2002). "A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with dysmotility type of functional dyspepsia". Z Gastroenterol 40: 401–8.
7. ^ Hanisch J, Bock P, Vinson B (2005). "The efficacy and safety of STW 5 versus Metochlopramide oral for functional dyspepsia under practice conditions (in German)". Med Klinik 100.
8. ^ Liechtle K (1999). "Experience reports on the use of Iberogast in children (in German)". Forschungsbericht Steigerwald Arzneimittelwerk GmbH.
9. ^ Veldhuyzen van Zanten SJ, Chiba N, Armstrong D, Barkun A, Thomson A, Smyth S, Escobedo S, Lee J, Sinclair P. A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in Helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study. Am J Gastroenterol. 2005 Jul;100(7):1477-88.
10. ^ Talley NJ, Meineche-Schmidt V, Pare P, Duckworth M, Raisanen P, Pap A, Kordecki H, Schmid V. Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies). Aliment Pharmacol Ther. 1998 Nov;12(11):1055-65.
11. ^ Meineche-Schmidt V, Talley NJ, Pap A, Kordecki H, Schmid V, Ohlsson L, Wahlqvist P, Wiklund I, Bolling-Sternevald E. Impact of functional dyspepsia on quality of life and health care consumption after cessation of antisecretory treatment. A multicentre 3-month follow-up study. Scand J Gastroenterol. 1999 Jun;34(6):566-74.

See also

• Gastritis
• Stomach ache
• Indigestion
• Functional bowel disorder

Biliary tree (Cholangitis, Cholestasis/Mirizzi's syndrome, PSC, Biliary fistula, Ascending cholangitis)

Malabsorption (celiac, Tropical sprue, Blind loop syndrome, Whipple's)

postprocedural: Gastric dumping syndrome - Postcholecystectomy syndrome