New NICE recommendations on dyspepsia will give more control to patients as well as reduce unnecessary endoscopies, as Professor Brendan Delaney explains
  • Dyspepsia in unselected patients in primary care is defined broadly to include patients with recurrent epigastric pain, heartburn, or acid regurgitation, with or without bloating, nausea or vomiting
  • Self-treatment with antacid and/or alginate therapy, taken as required, may be appropriate for many patients. However, additional therapy becomes appropriate to manage symptoms which persistently affect a patient’s quality of life
  • Urgent specialist referral or endoscopic investigation (to be seen within 2 weeks) is indicated for patients of any age with dyspepsia when presenting with any of the following: chronic gastrointestinal bleeding, progressive unintentional weight loss, progressive dysphagia, persistent vomiting, iron deficiency anaemia, epigastric mass or suspicious barium meal
  • Patients over the age of 55 years presenting with dyspepsia and without alarm signs do not require routine initial referral for endoscopy. However, endoscopy may be considered if symptoms persist despite H. pylori testing and initial PPI therapy, and patients have one or more of the following: previous gastric ulcer or surgery, continuing need for NSAID treatment and where the risk of gastric cancer or anxiety about cancer is heightened
  • Initial therapeutic strategies for dyspepsia are empirical treatment with a PPI or testing for and treating H. pylori. There is currently insufficient evidence to guide which should be offered first. A two week washout period following PPI use is necessary before testing for H. pylori with a breath test or a stool antigen test
  • If symptoms return after initial care strategies, step down PPI therapy to the lowest dose required to control symptoms. Encourage patients to use the treatment on an ‘on demand’ basis (taking therapy when symptoms occur) to manage their own symptoms
  • Offer patients requiring long-term management of symptoms for dyspepsia an annual review of their condition, encouraging them to try stepping down or stopping treatment
  • Offer H. pylori eradication therapy to H. pylori positive patients with peptic ulcer disease
  • Management of endoscopically determined non-ulcer dyspepsia involves initial treatment for H. pylori if present, followed by symptomatic management and periodic monitoring
  • Offer patients with GORD a full dose proton pump inhibitor (PPI) for one or two months
  • H. pylori can be initially detected using either 13C urea breath test, a stool antigen test or laboratory-based serology where locally validated

The term dyspepsia refers to a spectrum of upper gastrointestinal symptoms including epigastric pain and heartburn. Broadly defined in this way, dyspepsia is a very common condition; 40% of the adult population may suffer from dyspepsia, although only about 2% of the population consult their GP each year.1

The GP with an average list will therefore see one patient with dyspepsia every week. As dyspepsia is a chronic, relapsing and remitting condition, many of these patients will have experienced previous episodes, which may have been investigated by endoscopy or managed empirically (Table 1, below).

Table 1: Lifetime and annual recurrence risks for dyspepsia
Annual risk of recurrence
Duodenal ulcer (H. pylori positive)
Gastric ulcer (H. pylori positive)
Non-ulcer dyspepsia (overall)
Duodenal ulcer (H. pylori negative)
Gastric ulcer (H. pylori negative)
Reflux (overall)
Lifetime risk of recurrence
Duodenal ulcer (H. pylori positive)
Gastric ulcer (H. pylori positive)
Duodenal ulcer (H. pylori negative)
Gastric ulcer (H. pylori negative)
Non-ulcer dyspepsia (H. pylori positive)
Non-ulcer dyspepsia (H. pylori negative)
Reflux 80%

The range of potential management strategies for previously uninvestigated patients (endoscopy, acid suppression and Helicobacter pylori testing) and the need to consider the management of patients with a specific endoscopic diagnosis in the past makes any dyspepsia guideline quite a lengthy document.

The recently published NICE guideline, Dyspepsia: Management of dyspepsia in adults in primary care, replaces previous UK guidelines produced by the British Society of Gastroenterology, and also updates the NICE Technology Appraisal on proton pump inhibitors (PPIs).

Currently, prescribed drugs and endoscopies alone cost the NHS about £600 million annually, while over-the-counter medication costs patients £100 million.2 Although PPIs have recently started to come off patent and indeed become available from pharmacies, dyspepsia remains a costly condition and the guideline explicitly considered cost effectiveness as part of its remit. As the unit costs of dyspepsia therapies and investigations are moderate, effective treatments will also be cost effective.

In recent years, increasing evidence has accumulated as to the effectiveness of therapies for dyspepsia as well as the cost-effectiveness of management strategies in primary care.

The NICE guideline was developed in association with the Cochrane Collaboration Upper GI and Pancreatic Disease Collaborative Review Group, and Cochrane reviews were used exclusively; new reviews were conducted: peptic ulcer disease and gastro-oesophageal reflux disease (GORD), and existing reviews updated: non-ulcer dyspepsia and initial management strategies.

Economic models were constructed to examine cost-effectiveness. The guideline therefore reflects the most up-to-date evidence and is the most thorough in its approach to examining the quality of the evidence.

The guideline development group, consisting of GPs, academics and specialists, and pharmacists’ and patient representatives, met each month for a year. Evidence was presented and its implications then developed into a series of graded statements and flowcharts.

Stakeholders and referees were invited to comment on the guideline at draft stage.

The principal recommendations of the guideline are summarised in Box 1 (below).


The role of symptoms in the diagnosis of dyspepsia has long been a matter of controversy. Consensus statements over the past 15 years first excluded patients with sole heartburn, defined as gastro-oesophageal reflux disease (GORD),3 and subsequently patients with predominant heartburn.4 Although the logic of this is appealing, evidence shows that there is considerable overlap between heartburn and epigastric pain and that the predictive value of symptoms is poor in unselected patients from primary care.

In a large study from Canada, as many patients with heartburn had peptic ulcers as had epigastric pain.5 For this reason, the guideline recommends a common pathway of care for previously uninvestigated patients with both heartburn and epigastric pain.

In patients who have undergone endoscopy for a current or a previous similar episode that has excluded peptic ulcer disease, predominant heartburn should be managed as GORD and epigastric pain as non-ulcer dyspepsia (Figure 1, below).

Figure 1: Management flowchart for patients with GORD
Reproduced from Dyspepsia: Management of dyspepsia in adults in primary care by kind permission of the National Institute for Clinical Excellence

A flowchart for referral criteria and subsequent management is shown in Figure 2, below.

Figure 2: Flowchart of referral criteria and subsequent management
Reproduced from Dyspepsia: Management of dyspepsia in adults in primary care by kind permission of the National Institute for Clinical Excellence


Studies have shown that endoscopy does not significantly improve the outcome of management in patients with dyspepsia in comparison with empirical management strategies (H. pylori test or acid suppression).6 The role of endoscopy is in the detection of patients with potential malignancy.

The guideline recommends that endoscopy be used for the prompt investigation of patients with alarm symptoms (Box 2, below), and not simply because the patient is above a certain age.

Box 2: Alarm signs and symptoms of dyspepsia

Patient with dyspepsia

Immediate (same day) referral is indicated for:

  • Significant gastrointestinal bleeding
Urgent referral (within 2 weeks) is indicated at any age for:
  • Progressive dysphagia
  • Unintentional weight loss
  • Epigastric mass
  • Suspicious barium meal
  • Iron deficiency anaemia
  • Persistent vomiting
If treatment is unsuccessful, consider referring patients over 55 years old with:
  • Previous gastric ulcer
  • Previous gastric surgery
  • Pernicious anaemia
  • NSAID use
  • Family history of gastric cancer

There is no robust evidence that screening patients with dyspepsia to look for cancer is effective, and modelling suggests that it is not cost effective. Interestingly, a Danish study has shown that even alarm symptoms with dyspepsia are a poor predictor of upper gastrointestinal malignancy in that patients with dyspepsia and weight loss were as likely to have colorectal cancer as gastric cancer.7

Test and treat or PPI

The guideline recommends that patients should be managed with initial acid suppression using a PPI or by testing and treating for H. pylori.8 The rationale for this is that patients with peptic ulcer will benefit considerably; some patients with non-ulcer dyspepsia will benefit;9 and patients with GORD will be neither harmed nor cured.10

PPI therapy is an effective acid suppression therapy to gain control of a patient’s symptoms, which should then be further reviewed. The question of whether to use test and treat or PPI first is currently the subject of a large MRC trial.

Figure 3 (below) shows the management flowchart for patients with uninvestigated dyspepsia.

Figure 3: Management flowchart for patients with uninvestigated dyspepsia
Reproduced from Dyspepsia: Management of dyspepsia in adults in primary care by kind permission of the National Institute for Clinical Excellence

H. pylori testing

Currently, most patients tested for H. pylori in primary care are tested using serology. Unfortunately, this method indicates not only past and current infection, but, at a probable prevalence of H. pylori of 25%, only about 60% of patients with a positive test are actually likely to have infection. As false-positive tests lead to unnecessary use of antibiotics and cause confusion, the development group recommends the use of a 13C urea breath test, which has greater than 90% accuracy.11 Alternatively, stool antigen testing, which may be available in local laboratories, has similar accuracy.12

On-demand use of PPI

There is evidence for recommending that patients with non-erosive and mild oesophagitis whose symptoms are controlled on PPI may switch from continuous use to taking medication when they get symptoms, with good quality of life and acceptability. 13-15

The group felt that this was appropriate because it reduced PPI use by about 60% and also allowed patients to take control. The group extended the recommendation by extrapolation to patients with uninvestigated dyspepsia and those with non-ulcer dyspepsia.

Many of the guideline’s recommendations are based on direct application of consistent high quality evidence from randomised controlled trials.16 However, in areas where there was inconsistency, extrapolation to more general patient groups or longer timescales, the group graded the recommendation lower.

In particular, this applies to on-demand therapy where trials have only been in mild oesophagitis and of short duration, with the principal outcome being willingness to continue at 6 months.

The best quality evidence is for the use of PPIs in the healing of oesophagitis and the effect of H. pylori eradication on duodenal ulcer recurrence and non-ulcer dyspepsia.17

Practices should consider how they manage dyspepsia. Unfortunately, the development group was unable to recruit a practice nurse or nurse practitioner; however, nurses may have an important role in supervising breath tests and reviewing patients’ use of medication.

Urea breath test

The urea breath test can be prescribed and collected from the pharmacy by the patient.

Patients taking the test should stop taking PPIs for at least 2 weeks (they interfere with the test) and starve for 4 hours beforehand.

A small carton of orange juice (supplied by the patient) is used to delay gastric emptying and the patient produces a pre-dose breath sample by breathing into a tube through a straw.

The patient then drinks 13C labelled, non-radioactive urea solution and produces a second sample 20 minutes later. The tubes are sent by post to a laboratory for the difference in expired 13C CO2 to be determined by mass spectrometry.

Switching to the urea breath test is an important quality issue for practices, but staff should discuss local logistics and make sure that everyone is aware of the testing procedures. In particular, patients need careful supervision when producing the breath samples.

On-demand therapy

Patients already on PPIs will need to be reviewed to explain the rationale for on-demand therapy. Patients with previous oesophageal strictures should be kept on regular treatment.

New patients without alarm signs should be managed empirically; GPs can be confident in their approach and reassure anxious patients that they do not require endoscopy.

Patients over the age of 55 years with persisting symptoms may be referred for endoscopy to provide greater certainty in management if required.

The guideline is designed to empower patients to manage their symptoms using effective therapy on-demand.

We found little evidence to support lifestyle interventions, such as weight loss, dietary manipulation or raising the head of the bed, and suggest that patients should not be offered advice alone.

Although some patients may manage with reassurance and occasional symptomatic relief from antacids or alginates, most patients have consulted because these initial self-treatments have failed.

The guideline recognises that chronic dyspepsia can have a very significant effect on quality of life and that appropriate use of a PPI can be very effective.

Dyspepsia: management of dyspepsia in adults in primary care, NICE Clinical Guideline 17 can be downloaded from the NICE website:

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Click here to download a checklist to aid implementation of the NICE guideline on management of dyspepsia in adults in primary care

Guidelines in Practice, November 2004, Volume 7(11)
© 2004 MGP Ltd
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