Dyspepsia

Dyspepsia describes pain or discomfort in the upper abdomen, and has been defined in a variety of different ways by a number of expert groups.

• Prior to 1991, dyspepsia included patients with symptoms of heartburn and acid reflux.¹
• The Rome I definition defined patients with sole reflux symptoms as having gastro-oesophageal reflux disease (GORD) - also seen as 'GERD'.²
• More recently, these criteria have been extended to exclude patients with predominant reflux symptoms and symptoms suggestive of irritable bowel syndrome (IBS).³

The costs of managing dyspepsia outstrip all other conditions in the NHS. Expenditure on ulcer healing drugs and endoscopies costs the NHS in excess of £600 million.⁴ Dyspepsia is common, with an incidence of 2 per 1,000 population per year.⁵ Dyspepsia is also a lifelong, intermittent and relapsing disorder.

• As many as 3% of the population may be taking long-term prescribed medication for dyspepsia.⁶
• In any 6-month period 41% of the population will suffer an episode of dyspepsia and a quarter will have consulted their GP about their symptoms.⁷

• Epigastric discomfort
• Fullness or bloating
• Excessive flatus
• Nausea
• Fatty food intolerance

Always ask about family history and medication use.

• Peptic ulcer disease (10%)
• Oesophagitis (15%)
• No significant abnormality (non-ulcer dyspepsia or functional dyspepsia - 75%)

Older patients are more likely to have serious disease.

• Always check for abdominal mass
• Consider taking FBC to demonstrate another alarm feature, e.g. iron deficiency anaemia
• Testing for Helicobacter pylori is worthwhile. Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) have 2 to 4 times the risk of ulceration if H. pylori is positive.¹⁰ Testing patients for H. pylori and eradication before starting NSAIDs reduces the incidence of ulcers.¹¹

• Peptic ulcer
• Functional (non-ulcer) dyspepsia
• IBS
• Atypical GORD/GERD
• Biliary pain, e.g. gallstones
• Achalasia
• Medication-induced dyspepsia
• Aerophagia
• Oesophageal spasm
• Carcinoma of oesophagus or stomach

Exclude abdominal mass and other causes of abdominal pain.

For patients without alarm features and with previous investigations for dyspepsia

It is possible to treat on the basis that a similar pathology has recurred, although refer to specialist if unresponsive to treatment or the diagnosis is in doubt.

• If peptic ulcer previously and no evidence of H. pylori eradication, prescribe H. pylori eradication therapy if test is positive. If previous eradication therapy, use breath test to determine if successful and re-eradicate if necessary.
• If oesophagitis previously, prescribe proton pump inhibitor (PPI).¹³
  • The National Institute for Health and Clinical Excellence (NICE)⁴ suggests full-dose PPI for 1-2 months and then titrating down to low dose or as required dosage if symptoms allow (and there is no underlying condition or co-medication requiring ongoing treatment).
  • Where there is no initial response (and recent endoscopy has shown GORD), a further month of double dose may be tried, followed by a month of H2-receptor antagonist (H2RA).
  • Prokinetic agents are not recommended. NICE says that cisapride is no longer licenced whilst the evidence for metoclopramide and domperidone is limited.⁴
  • The H2RAs provide a swift and effective means of acid suppression and can be used intermittently to achieve control of symptoms. The PPIs are more prolonged in action, produce more profound acid suppression and are more expensive. Their greater efficacy may still provide value for money.
  • Some patients may require prolonged high doses of PPI, and may ultimately be candidates for anti-reflux surgery.
• Where patients have reflux, but endoscopy failed to show oesophagitis, try full dose PPI for a month, followed by a month of H2RA.
• If none of the above (non-ulcer dyspepsia), H. pylori eradication (after a positive test) may relieve symptoms in 1 in 20 patients (NNT = 20)¹⁴
• If none of the above and predominant heartburn symptoms (endoscopy-negative reflux disease), prescribe H2RA, or PPI if not controlled.¹⁵
• If none of the above and predominant epigastric pain, an H2RA is the least costly.¹⁶

For the uninvestigated patient without alarm features

The NICE guideline suggests the following steps:

• Review medications: possible drug causes of dyspepsia include NSAIDs, steroids, calcium antagonists, nitrates, theophyllines, bisphosphonates. Reduce or stop if possible.
• Lifestyle advice, i.e. stopping smoking, more regular meals, ceasing excessive alcohol consumption.
• Antacids are cheap, simple and may be all that is required for relief of occasional symptoms. Most antacids contain a mixture of aluminium hydroxide that tends to cause constipation and magnesium hydroxide that tends to cause diarrhoea. The balance between the two cannot be assured and there may be disturbance of bowel function. If a large amount of antacid is being consumed, consider acid suppression.
• Try either of the following. The alternative choice can be tried if symptoms persist or return:
  • Test for H. pylori (Carbon-13 urea breath test, stool antigen or lab serology) and eradicate if positive.
  • Empirical acid suppression (with PPI) - full dose for one month.

Where there has been a satisfactory response at any of the steps above, reassure and return to self-care.
If the patient responds to PPI but then relapses, consider low-dose or intermittent treatment.
If there is no response, consider a prokinetic, e.g. metoclopramide or H2RA, e.g. ranitidine for one month.
Where patients show an inadequate response to treatment, consider other diagnoses, e.g. gallstones and/or referral to a specialist.

H. pylori eradication

If the infection is suspected or demonstrated, eradication is the logical course of action. NICE suggests that eradication should be offered if a test is positive.

There are several regimes that are available. They usually consist of high-dose acid suppression with a PPI and two antibiotics, also at quite high dose. The usual recommended duration of treatment is seven days and it is said to give eradication in about 90% of cases. A 14 days' course may produce a higher rate of eradication but the incidence of adverse effects may make compliance poor. Diarrhoea is common with two antibiotics at high dose.

The following is based on the recommendations of NICE:⁴

• Omeprazole 20 mg
• Amoxicillin 1000 mg
• Clarithromycin 500 mg

All are taken twice-daily for seven days.

An alternative regimen with a similar eradication rate of around 90% is:

• Omeprazole 20 mg
• Clarithromycin 250 mg
• Metronidazole 400 mg

All are taken twice-daily for seven days.
There is probably no difference between the various PPIs available, provided that they are used at equivalent dose and this is a matter of personal choice. It would be reasonable to have local protocols based upon local patterns of antibiotic resistance.¹⁷ Resistance to metronidazole, in particular, is highly variable.

If there is failure of treatment, this is usually due to poor compliance or antibiotic resistance:

• If there was poor compliance, a more tolerable regimen may be required.
• Resistance can even develop during treatment, especially with a single antibiotic. A further attempt at eradication may be made. The regimen should be adjusted according to the nature of the problem. The organism may have been cultured after endoscopy so it may be possible to obtain sensitivities.

It is common practice to use four drugs for a repeated attempt. The antibiotics can be changed and chelated bismuth may be used. A typical quadruple therapy would be:

• PPI twice a day
• Bismuth 120 mg four times a day
• Metronidazole 400 mg three times a day
• Oxytetracycline 500 mg four times a day

All regimes are taken for seven days.
Reinforce the importance of compliance, as it is not easy to take so many tablets so many times a day, even for just a week. Chelated bismuth is rather unpleasant to take but it is effective at helping to eradicate H. pylori.

Pharmacological issues

• During H. pylori eradication, abdominal discomfort and diarrhoea are very common but the patient should be encouraged to persist to achieve eradication and to heal the ulcer permanently. Lactobacilli, usually ingested in the form of natural unpasteurised yoghurt, may be of value in replacing the natural flora of the gut and they may also have a suppressive effect on H. pylori.¹⁸
• Adverse reactions to PPIs and H2RAs are usually rare and mild but severe problems can arise. Rare but not serious problems may include taste disturbance, peripheral oedema, photosensitivity, fever, arthralgia, myalgia and sweating. Serious problems include liver dysfunction, hypersensitivity reactions (including urticaria, angioedema, bronchospasm, anaphylaxis), depression, interstitial nephritis, blood disorders (including leucopenia, leucocytosis, pancytopenia, thrombocytopenia) and skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous eruption).
• Many of the drugs used in the management of peptic ulcer disease carry a warning that they should not be used in pregnancy or whilst breast-feeding. This is usually because of lack of information about safety in pregnancy rather than evidence of adverse effects in pregnancy. However, misoprostol - a prostaglandin analogue - should be avoided in pregnancy as it may cause abortion.
• PPIs are metabolised mostly in the liver. In liver disease, dose adjustment may be required for omeprazole, pantoprazole, and esomeprazole. There are no data on the use of rabeprazole in people with severe hepatic impairment, so the manufacturer advises caution.
• Omeprazole and esomeprazole may interfere with warfarin monitoring.

Patients should be reviewed at the end of a course of treatment, especially H. pylori eradication, to confirm a satisfactory outcome.
If simple acid suppression is given, the patient should be reviewed after one or two months to ascertain that the end is being achieved and there are no warning signs such as weight loss to suggest malignancy.

Routine endoscopic investigation of dyspeptic patients is not necessary, but should be considered in patients over age 55 where symptoms persist despite H. pylori testing and acid suppression.⁴

However, there has been some dissent over the NICE recommendations, citing the value of early detection of GI cancer and its improved survival rates.¹⁹

1. No authors listed; Management of dyspepsia: report of a working party. Lancet. 1988 Mar 12;1(8585):576-9.
2. Talley NJ, et al; Functional dyspepsia: A classification with guidelines for diagnosis and management. Gastroenterol. Int. 1991 4:145-160.
3. Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE. Rome II: The functional gastrointestinal disorders. Allen Press: Lawrence KS USA, 2000.
4. Dyspepsia: Managing dyspepsia in adults in primary care, NICE Clinical Guideline (2004)
5. McCormick A, Fleming D, Charlton J. Morbidity statistics from General Practice. Fourth national morbidity study 1991-1992. London: Office of Population Censuses and Surveys., 1995;
6. Ryder SD, O'Reilly S, Miller RJ, et al; Long term acid suppressing treatment in general practice. BMJ. 1994 Mar 26;308(6932):827-30. [abstract]
7. Jones RH, Lydeard SE, Hobbs FD, et al; Dyspepsia in England and Scotland. Gut. 1990 Apr;31(4):401-5. [abstract]
8. Hansen JM, Bytzer P, Schaffalitzky De Muckadell OB; Management of dyspeptic patients in primary care. Value of the unaided clinical diagnosis and of dyspepsia subgrouping. Scand J Gastroenterol. 1998 Aug;33(8):799-805. [abstract]
9. Talley NJ, Weaver AL, Tesmer DL, et al; Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy. Gastroenterology. 1993 Nov;105(5):1378-86. [abstract]
10. Hawkey CJ, Tulassay Z, Szczepanski L, et al; Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention. Lancet. 1998 Sep 26;352(9133):1016-21. [abstract]
11. Chan FK, Sung JJ, Chung SC, et al; Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997 Oct 4;350(9083):975-9. [abstract]
12. Referral for suspected cancer, NICE Clinical Guideline (2005)
13. Chiba N, De Gara CJ, Wilkinson JM, et al; Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997 Jun;112(6):1798-810. [abstract]
14. Moayyedi P, Soo S, Deeks J, et al; Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD002096. [abstract]
15. van Pinxteren B, Numans ME, Bonis PA, et al; Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2006 Jul 19;3:CD002095. [abstract]
16. Moayyedi P, Soo S, Deeks J, et al; Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001960. [abstract]
17. Cameron EA, Powell KU, Baldwin L, et al; Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK, 1991-2001.; J Med Microbiol. 2004 Jun;53(Pt 6):535-8. [abstract]
18. Wang KY, Li SN, Liu CS, et al; Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr. 2004 Sep;80(3):737-41. [abstract]
19. Griffin SM, Bowrey DJ, Allum WH. Upper gastrointestinal surgeons comment on NICE dyspepsia guidelines BMJ; February 5th, 2005
20. Foy R, Parry JM, Murray L, et al; Testing for Helicobacter pylori in primary care: trouble in store? J Epidemiol Community Health. 1998 May;52(5):305-9. [abstract]
21. Delaney BC, Moayyedi P, Forman D; Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2003;(2):CD001961. [abstract]

• Dyspepsia - proven gastro-oesophageal reflux disease, Clinical Knowledge Summaries (June 2008)
• Dyspepsia - unidentified cause, Clinical Knowledge Summaries (2008)
• Dyspepsia - proven peptic ulcer, Clinical Knowledge Summaries (June 2008)
• Dyspepsia - proven non-ulcer dyspepsia, Clinical Knowledge Summaries (2008)
• Endoscopy. A surgeon describes what an endoscopy is, what happens during the procedure, and how you can prepare yourself for it. A short video from NHS Choices. (June 2008)