Management of dyspepsia

Advisory report | 12-12-2000

The Committee has concentrated principally on primary healthcare because patients with dyspepsia are predominantly treated by their GP.

Cases of dyspepsia are a frequent occurrence: according to a Dutch survey, more than 350,000 patients consult their GP annually. Of these, more than 50,000 are patients with gastric ulcers and more than 60,000 patients with reflux disease (heartburn or acid regurgitation). In about 60% of cases no anatomical abnormalities such as ulcer or inflammation can be found, in which case this is referred to as functional dyspepsia. It appears that, apart from the severity and duration of the disorders, the decision to consult a doctor is often based on the fear of a severe, and particularly malignant, disorder. In the absence of specific symptoms, however, dyspepsia complaints in general are not predictive of a malignant disorder. Gastric cancer is diagnosed in about 2000 patients annually and oesophageal cancer in about 1000. The number of cases of gastric ulcer and gastric cancer has shown a tendency to decline for many years; the number of cases of oesophageal cancer is increasing.

The causes of most cases of dyspepsia are not known. The discovery in the 1980s that ulcers are usually caused by an Hp infection marked a major advance in gastroenterology, providing an effective treatment. In the euphoria that followed, however, Hp infection was held responsible by some authors for more stomach disorders than actually warranted by the facts. A proper sense of proportion is now being restored with respect to the importance of this infection. Hp infection plays no significant role in the majority of patients with functional dyspepsia. With respect to reflux disease, there is even evidence that the infection confers a certain degree of protection. In the Western world, moreover, the spread of Hp is on the decrease. Although Hp infection still represents a major cause of ulcers, other causes are increasingly coming to the fore. In the US, ulcers are now increasingly being found in people without Hp infection. Greater attention should also be paid to Hp-negative ulcers in Europe.

Drugs also are an important cause of dyspepsia. NSAIDs in particular are the main cause of non-Hp-induced ulcers. The significance of other factors, such as hereditary factors, smoking, stress, obesity, diet and alcohol as risk factors for dyspepsia, is less clear.

Diagnosis

Because cases of dyspepsia often regress spontaneously, extensive diagnostic investigations are usually unnecessary. On the basis of the pattern of symptoms and a simple physical examination, three groups may be usefully distinguished:

• patients with warning symptoms, which may indicate complications of a gastric ulcer or a malignant disorder and in whom further investigations and specific treatment are of immediate importance
• patients with reflux complaints (heartburn or pain behind the breastbone) in whom a trial treatment with gastric acid inhibitors may be indicated
• all other patients, in whom treatment as though for functional dyspepsia is most appropriate.

According to the Committee, further differentiation of patients with disorders suggestive of ulcer and patients with motility disorders (nausea, sensation of distension and rapid satiation), as is the case in current guidelines, is not useful because it has no predictive value for underlying disorders and is of equally little importance for treatment.

Supplementary investigations, particularly for the presence of an ulcer, are necessary if:

• it is not possible to discontinue drug treatment gradually once it has been instituted
• the complaints do not regress under the effect of the treatment
• the disorders recur.

Preference should be given here to endoscopic examination since this enables all relevant conditions to be detected: ulcer, inflammation of the mucous membrane or a malignant condition. Where necessary, biopsies can be taken for further investigations of Hp infection, determination of the susceptibility to antimicrobial agents and malignancy. However, because many patients find the endoscopic examination stressful, a test for Hp infection can be used to select patients for endoscopy. The endoscopic examination is then confined to patients with the infection. If the complaints persist, however, endoscopy should be performed, even in the event of a negative Hp test, in order to rule out other conditions. In patients taking NSAIDs, the Committee advises against first of all performing Hp diagnostic investigations.

Therapy

Both H2 antagonists and proton pump inhibitors have proved effective in reflux complaints/reflux disease. Because all cases of dyspepsia in which heartburn is the predominant feature are currently considered to be reflux complaints, there is a very wide spectrum in terms of the severity of the symptoms. In many patients, therefore, the use of proton pump inhibitors is unnecessary. Moreover, it is important that even after short-term use of proton pump inhibitors a so-called rebound phenomenon is described, as a result of which it is difficult for the patient to discontinue treatment once it has been instituted. In patients with reflux disorders who require drug treatment, the Committee therefore recommends starting treatment with H2 antagonists. Where necessary these may be switched to proton pump inhibitors. Drug therapy should be gradually discontinued after a two- to four-week course of treatment. In a minority of cases permanent treatment is necessary.

In patients with functional dyspepsia, establishing a good doctor-patient relationship, taking the complaints seriously and reassurance are important factors in treatment. It has not been irrefutably established that any drug has a beneficial effect on the disorders. As this involves the largest group of patients, there is a serious need for further study of effective treatments.

On the basis of published data concerning efficacy, resistance, ease of use (treatment compliance) and side effects, two triple therapies may be considered for first-line therapy: clarithromycin plus amoxicillin combined with a proton pump inhibitor or clarithromycin plus amoxicillin combined with ranitidine bismuth, both regimens for seven days. The Committee recommends undertaking diagnostic tests for Hp infection in all ulcer patients. If an ulcer appears during the administration of an NSAID, the need for the NSAID and the choice of the specific drug, must be reviewed. Hp infection and NSAID cause ulcers in different ways and there is no marked interaction between the two. It is not proven that Hp eradication in general has a beneficial effect in respect of NSAID-related ulcers.

In the Committee’s opinion, the preventive use of gastroprotective agents concomitantly with NSAIDs is only necessary if specific risk factors are present. These include a previous ulcer when using NSAIDs, the use of exceptionally high NSAID doses, advanced age, severe disorders other than ulcers, use of corticosteroids or anticoagulants, and moderate or severe forms of rheumatoid arthritis. On the basis of prescription data, however, it seems likely that gastroprotective agents are frequently prescribed even when these factors do not play a role.

Two groups of patients deserve particular attention:

• Patients in whom an ulcer was diagnosed in the past but who did not have a diagnosis of Hp infection and eradication of the bacterium at the time. In the Committee’s opinion, this should be done in the event of a recurrence of the disorders or chronic recurrent drug use.
• Patients who take gastric acid inhibitors chronically or recurrently without a specific diagnosis (gastric ulcer or reflux disease). In the opinion of the Committee, drug use can in most cases be gradually discontinued in these patients. If, however, this does not succeed or if the complaints recur, endoscopic investigation is indicated, for this situation too might involve an ulcer amenable to treatment.

Guidelines and scientific research

The Committee agrees in general with the existing guidelines of the Dutch College of General Practitioners (NHG). On the basis of recent insights, it makes some recommendations for revision. Study data show, however, that in practice the guidelines are often not followed. This applies above all to recommendations on starting treatment with relatively simple and safe medicines, on supplementary investigations for persistent or recurrent complaints which require the long-term use of gastric acid inhibitors, and on diagnosis and treatment of Hp infection in patients with a previously detected ulcer. In the Committee’s view, initiatives that have already been carried out in some general practice groups to improve the implementation should be generally applied.

The Committee is of the opinion that care of patients with dyspepsia is often hampered by a lack of knowledge. This applies specifically to treatment of functional dyspepsia and reflux disease. The Committee makes some recommendations for further research in this respect.