American Journal of Gastroenterology ISSN 0002-9270

C 2005 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2005.00225.x
Published by Blackwell Publishing

PRACTICE GUIDELINES

Guidelines for the Management of Dyspepsia
Nicholas J. Talley, M.D., Ph.D., F.A.C.G.,1 Nimish Vakil, M.D., F.A.C.G.,2 and the Practice Parameters
Committee of the American College of Gastroenterology
1
Division of Gastroenterology and Hepatology, Mayo Clinic, Clinical Enteric Neuroscience Translational and
Epidemiological Research Program, Mayo Clinic, Rochester, Minnesota; and 2 University of Wisconsin Medical
School and Marquette University College of Health Sciences, Milwaukee, Wisconsin

Dyspepsia is a chronic or recurrent pain or discomfort centered in the upper abdomen; patients with predominant
or frequent (more than once a week) heartburn or acid regurgitation, should be considered to have
gastroesophageal reflux disease (GERD) until proven otherwise. Dyspeptic patients over 55 yr of age, or those with
alarm features should undergo prompt esophagogastroduodenoscopy (EGD). In all other patients, there are two
approximately equivalent options: (i) test and treat for Helicobacter pylori (H. pylori) using a validated noninvasive
test and a trial of acid suppression if eradication is successful but symptoms do not resolve or (ii) an empiric trial
of acid suppression with a proton pump inhibitor (PPI) for 4–8 wk. The test-and-treat option is preferable in
populations with a moderate to high prevalence of H. pylori infection (≥10%); empirical PPI is an initial option in
low prevalence situations. If initial acid suppression fails after 2–4 wk, it is reasonable to consider changing drug
class or dosing. If the patient fails to respond or relapses rapidly on stopping antisecretory therapy, then the
test-and-treat strategy is best applied before consideration of referral for EGD. Prokinetics are not currently
recommended as first-line therapy for uninvestigated dyspepsia. EGD is not mandatory in those who remain
symptomatic as the yield is low; the decision to endoscope or not must be based on clinical judgement. In patients
who do respond to initial therapy, stop treatment after 4–8 wk; if symptoms recur, another course of the same
treatment is justified. The management of functional dyspepsia is challenging when initial antisecretory therapy
and H. pylori eradication fails. There are very limited data to support the use of low-dose tricyclic antidepressants
or psychological treatments in functional dyspepsia.
(Am J Gastroenterol 2005;100:2324–2337)

INTRODUCTION as a subjective negative feeling that is nonpainful, and can
incorporate a variety of symptoms including early satiety
These and the previous guidelines were developed under or upper abdominal fullness. Patients presenting with pre-
the auspices of the American College of Gastroenterol- dominant or frequent (more than once a week) heartburn
ogy and its Practice Parameters Committee and approved or acid regurgitation should be considered to have gastro-
by the Board of Trustees. The world literature was re- esophageal reflux disease (GERD) until proven otherwise.
viewed extensively using the National Library of Medicine Dyspepsia is a common complaint in clinical practice;
database. Appropriate studies were reviewed and any ad- therefore, its management should be based on the best ev-
ditional studies found in the reference list of these papers idence. Dyspepsia has often been loosely defined; the most
were obtained and reviewed. Evidence was evaluated along a widely applied definition of dyspepsia is the Rome Work-
hierarchy, with randomized, controlled trials given the great- ing Teams formulation, namely chronic or recurrent pain or
est weight. Abstracts presented at national and international discomfort centered in the upper abdomen (1). Predominant
meetings were only used when unique data from ongoing epigastric pain or discomfort helps to distinguish dyspepsia
trials were presented. When scientific data were lacking, from GERD; in the latter the dominant complaint is typically
recommendations were based on expert consensus obtained heartburn or acid regurgitation but there may be a distinct
from both the literature and the experience of the authors epigastric component that is confusing (2). Frequent reflux
and the Practice Parameters Committee. Each guideline was symptoms (twice a week or more) probably impair quality
evaluated by the committee and the strength of evidence to of life and are generally considered to identify GERD until
guide clinical practice was assessed using established criteria proven otherwise (3–6). Clinical trials in dyspepsia have used
(Table 1). various definitions and have often not distinguished obvious
GERD from dyspepsia, making interpretation of treatment
DEFINITIONS responses problematic.
Discomfort has been defined by the Rome Working Teams
Dyspepsia is defined as chronic or recurrent pain or discom- as a subjective negative feeling that is nonpainful, and
fort centered in the upper abdomen. Discomfort is defined has been considered to incorporate a variety of symptoms

2324

however. I Evidence from RCTs with low false positive rates (i. progressive dysphagia. Acute self-limited dys. bloating. if eradication is successful but symptoms do not resolve wide. unless completely new symptoms or may be exaggerated (9). Hence. significant p values). or (ii) an empiric trial of acid suppression with a proton mately 25%. Repeat EGD is otherwise unlikely less than 1% over 3 months has been reported (10). adequate sample sizes (low likelihood of type II errors) and appropriate methodology (low NATURAL HISTORY AND COSTS OF DYSPEPSIA likelihood of type I errors) II Evidence from RCTs with high false positive rates.102:305S. Belching alone is also an weight loss (>10% body weight). but how many had en- Note: Adapted from Guyatt GH et al. esophagogastric malignancy. although it is commonly present trointestinal cancer. evidence from other level I studies or supported by only one level I or two or more level II studies amongst those with epigastric pain only 9% had a peptic C Supported by level III–V evidence ulcer and 14% had reflux esophagitis. dyspepsia patients tended to remain symptomatic with 61% using drugs and 43% hav- Note: Adapted from Cook D et al. Graded Recommendations for Clinical Practice Reassurance after endoscopy: C Grade Strength of Evidence to Guide Clinical Practice Very few studies have investigated dyspepsia subjects from A Supported by two or more level I studies without the community by esophagogastroduodenoscopy (EGD) and conflicting evidence from other level I studies other tests. the number of subjects who develop dyspepsia Grades of evidence: is matched by a similar number of subjects who lose their Early endoscopy for alarm symptoms: C Test-and-treat strategy for H. JAMA 1995. Levels of Evidence symptoms. with epigastric pain or discomfort. but in Sweden a total societal cost of $63 per adult contemporaneous cohort of controls was calculated for dyspepsia (including reflux disease) (11). The costs in the United States remain poorly doc- III Evidence from nonrandomized trials using a umented.e. upper abdominal fullness. Chest 1992. JAMA Press 2001. In a population-based study from northern Norway. approximately 9% of people who had no symptoms of Some anxious patients may need the reassurance af- dyspepsia anually in the prior year reported new symptoms forded by endoscopy. insufficient symptom to identify dyspepsia and can be sec. The test-and-treat option symptoms (7). Whatever to ever be cost-effective. or those with ditions. out peptic ulcer disease.274:1800–1804. Guidelines for the Management of Dyspepsia 2325 Table 1. ing gastrointestinal procedures. a family history of gas- ondary to air swallowing. to determine the underlying causes of the symp- B Supported by two or more level I studies with conflicting toms. or inappropriate methodology ondary care. The prevalence is lower if patients with any is preferable in populations with a moderate to high preva- symptoms of heartburn and regurgitation are excluded (8). Dyspeptic patients more than 55 yr old. previous documented peptic ulcer. or an pepsia generally requires no investigation and will not be abdominal mass) should undergo prompt endoscopy to rule further considered here in these management guidelines. anemia. Nausea can be secondary to a variety of nonabdominal con. lence of H. the point prevalence is approxi. In Scandinavia. In the United PPI strategy is preferable in low prevalence situations. Dyspepsia is usually a chronic condition in primary and sec- inadequate sample sizes. In patients aged 55 yr or younger with no alarm features. On the other hand. 288 adult primary care patients with dys- of controls V Evidence from case series without controls pepsia were followed up for 1 yr. the clinician may consider two approximately equivalent EPIDEMIOLOGY OF DYSPEPSIA management options: (i) test and treat for H. repeat EGD is on follow-up.102:305S. previous esophagogastric malignancy. However. pylori infection (≥10%). and Cook D et al.. parable study from northern Sweden. In the United States. explaining the observation that the prevalence re- Level mains stable. odynophagia. an incidence rate of alarm features develop. including early satiety. persistent vomiting. Users Guides to doscopy negative reflux disease is uncertain (13). those with a past history of dyspepsia not recommended once a firm diagnosis of functional dys- or peptic ulcer were not excluded and hence the onset-rate pepsia has been made. neither bloating nor nausea alone should be alarm features (bleeding. or nausea (1). whereas the empirical The incidence is more poorly documented. indicating intensive use of medical resources (12). Chest 1992. pylori using a validated noninvasive test and a trial of acid suppression It is established that dyspepsia is a common problem world. In a com- the Medical Literature. pylori: A Acid suppression therapy: A Table 2. lymphadenopathy. IV Evidence from nonrandomized trials using a historical cohort In another study. unexplained considered to identify dyspepsia. bloating is most typically a symptom of DIAGNOSTIC TESTING IBS and may not be located in the upper abdomen exclusively. the incidence. a similar proportion of . and other rare upper gastrointestinal tract disease. excluding those people who have typical GERD pump inhibitor (PPI) for 4–8 wk. States. early satiety.

mended by the Rome Committees. Age < 55 PATHOPHYSIOLOGICAL DISTURBANCES IN Age > 55 or alarm features No alarm features ENDOSCOPY-NEGATIVE (FUNCTIONAL) DYSPEPSIA Approximately 40% of patients with functional dyspepsia HP prevalence HP prevalence > 10% <10% have delayed gastric emptying (27). 17). hour esophageal pH testing can identify pathological acid In a barostat study. male gender and normal their symptoms based on EGD. these patients are not excluded from the functional dyspepsia diagnosis category (26). Dyspepsia (uninvestigated) uncertain. tion including gastric ultrasound. low body weight. and gastric cancer is relatively rare in western populations evidence that a gastric emptying test cost-effectively alters (16. and hence patients with or delayed gastric emptying (37). and severe vomiting were independently associated with delayed gastric emptying of solids (28). Endoscopic ultrasonog. while postprandial al. in a Canadian study symptoms. Additional diagnostic testing over and above EGD has a There is evidence that the stomach and other regions of low yield in dyspepsia. pylori. ported in 160 patients with functional dyspepsia that one third raphy (EUS) has been reported to have a higher yield of had gastric hypersensitivity and this abnormality was associ- identifying pancreatico-biliary pathology but selection bias ated with increased postprandial pain as well as belching and may explain the observation and much of the pathology iden. one was character- pepsia presenting to primary care have no obvious cause for ized by predominant epigastric pain. recently re- that needs no intervention (18. extensively evaluated a group of patients with functional symptoms were more often evoked with a meal in functional dyspepsia. Studies apply. this in. failed to replicate these findings. but (29). nausea. Consider EGD Consider EGD presence of relevant and severe postprandial fullness. tis. Moreover. (a “stiff fundus”) was found in 40%. in 343 Italian patients reported Test and treat for H pylori PPI trial that delayed gastric emptying was significantly more frequent Fails Fails in patients characterized by female sex. ciated with a failure of fundic relaxation (38). 19). hence.2326 Talley et al. including minor delays in gastric empty. it is controver- EGD sial whether a specific symptom profile is associated with Test and treat PPI trial for H. and a second by predominant nonpainful North America is probably esophagitis. Twenty-four associations (35). also reported that delayed gastric empty- this study did include patients with heartburn (15). however. weight loss. but the pending on the background prevalence of H. . and MRI. but the clinical relevance in most cases is (39). The most common finding in gastric emptying. Many people with dys. they reported that 47% had abnormal findings on dyspepsia. testing is available to assess abnormal fundic accommoda- ing and lactose intolerance remains questionable (22). although this few abnormalities aside from asymptomatic cholelithiasis applies only in a subgroup (32–36). pylori. impaired gastric accommodation to a meal endoscopic diagnosis of functional dyspepsia (22–25). clinical relevance of identifying this abnormality remains in fection will be identified in 20–60% of patients with func. have failed to identify a definite support the view that only a minority of patients presenting symptom profile associated with delayed gastric emptying with dyspepsia have peptic ulcer disease or reflux esophagi. although 32% with Italian group identified distinct subgroups based on predom- esophagitis were asymptomatic (14). Klauser et et al. there was no clear symptom profile that was asso- additional testing but the significance of the various abnor. and this abnormality ever. Other studies. Noninvasive malities identified. pylori delayed gastric emptying. However. Stanghellini et al. but confirmatory data are needed on the symptom tified is of questionable significance (20. ated irritable bowel syndrome and delayed gastric emptying tients had erosive esophagitis and only 5% a peptic ulcer. Tack et al. Algorithm for the management of uninvestigated dyspepsia relevant and severe postprandial fullness. However. SPECT. management is not available. Tack et al. inant symptoms and gastric emptying. studied patients with func- reflux in approximately 20% of patients with a clinical and tional dyspepsia. In a separate study of 483 patients. some dispute in terms of defining therapeutic interventions tional dyspepsia. the symptom criteria used to define functional dyspep. Boeckxstaens typical reflux symptoms contaminated the studies. 21). suggesting there is not a simple association (31). De. Figure 1. and absence of severe epigastric pain. hypersensitivity to gastric distention. vomiting. 43% of 1. Studies ing was associated with postprandial fullness and vomiting from open-access endoscopy practices and outpatient series (30). was associated with early satiety and weight loss but not with sia in these studies have generally been broader than recom. and a high frequency of associ- of uninvestigated dyspepsia in primary care. How. Sarnelli et al. female gender. female sex. the same subjects had peptic ulcer or esophagitis. presence of H. at least in primary care.040 pa. the gut including the duodenum and esophagus are hyper- ing abdominal ultrasonography in dyspepsia have reported sensitive to distention in functional dyspepsia. and whether changes in gastric Fails emptying can predict symptom improvement in functional Fails dyspepsia.

an abdominal of gastric emptying of the nutrient meal as well as relaxation mass. (rather than 45 yr) seems a reasonable cut-off because cancer resent simple tests of the ability of a patient to drink water is rare in younger patients in the United States. These rep. 48). previous modulate the test results. There are regions in the United States of dyspepsia into ulcer-like or dysmotility-like dyspepsia based high cancer incidence where lower age thresholds may need on symptom patterns or predominance. jaundice. individual symptoms. which may need to be New-onset dyspepsia in older age is an alarm feature or red refined after the patient has initially had a trial of therapy. ing which drug and for how long. Some have found that the drink gastric surgery or malignancy. symptom subgroups. few patients younger than 55 yr of age SYMPTOMS AND SYMPTOM SUBGROUPS with an upper gastrointestinal malignancy present without alarm symptoms. tually be presenting not necessarily because of the symptoms It is thus controversial whether subdividing dyspepsia into per se but because of a fear of serious disease or recent psy- symptom subgroups aids management in documented func. chological distress. A study from Canada reported that the ascertain the likely cause of the symptoms and exclude under- patient’s dominant symptom (including heartburn) failed to lying serious structural disease. However. considered the gold standard to ensure that malignancy has pepsia (15. this is a stomach “stress test” and can sia. but no age or a nutrient load such as Ensure
until they feel completely threshold is absolute (47). 43). DISEASE IN UNINVESTIGATED DYSPEPSIA but fear of serious disease probably explains only some health The risk of malignancy increases with age and therefore care seeking behavior (53). and have more symptoms 30 min after reach. as gastric cancer is very rare in the United States below the age of 45 yr although it increases A number of management options are available to the clin- thereafter (44). antisecretory therapy can mask a cancer at endoscopy (49) physiological abnormalities of uncertain relevance are not but does not appear to alter the outcome (50). Currently. The water-load test and nutrient-load test may help identify The optimal age threshold for endoscopy is unclear but 55 yr gastric dysfunction in clinical practice (40. or other patho. These include unexplained weight objectively quantify postprandial distress. and the rate gia. Hence. On the basis of expert symptom subgroups could identify more homogenous pop. Upper gastrointestinal ma- tests correlate with fundic dysaccommodation rather than lignancy is rarely present in young patients without alarm visceral hypersensitivity (42). vomiting. opinion. Use of turbances. evidence- derlying peptic ulcer disease. patients with gastroduodenal motility dis. However. Some studies have reported that older age is an ician in younger patients with no alarm features with un- independent risk factor for identifying underlying structural investigated dyspepsia. ALARM FEATURES AND IDENTIFICATION OF STRUCTURAL The patient requiring major reassurance needs to be dif- ferently managed than one who does not have such concerns. abnormalities. but the positive predictive value of alarm features strate a relationship to gastric dysfunction while some data remains very poor (47. or a history of peptic ulcer. but the results have been inconsistent (45. The American College of Physicians in 1985 published a guideline recommending that patients who were over the MANAGEMENT OPTIONS IN YOUNGER PATIENTS WITH NO age of 45 deserved referral for prompt endoscopy to rule ALARM FEATURES out underlying malignancy. it was postulated that to be considered such as Alaska (51). Working teams have suggested subdividing not been missed. The physician generally wishes to functional dyspepsia. this test is highly unlikely to alter management. normal loss. if an EGD has already been done recently. flag. Although alarm symptoms are not specific for a serious underlying disorder. prompt EGD is be used to identify structural disease in uninvestigated dys. includ- uals over 55 yr of age who develop new dyspeptic symptoms. 46). plied to try and identify serious underlying disease in dyspep- ing satiation. A long history of symptoms in suggest these tests correlate with psychological disturbances patients should make cancer unlikely but a symptom dura- (40. a family history of upper gastroin- of the fundus secondary to meal ingestion can potentially testinal tract cancer. features. 41). 7). cide whether pharmacological therapy is required. the patient may ac- predict endoscopic findings in a primary care population (15). odynophagia. tion threshold has not been defined in the literature. repeating ulations that would respond to targeted medical therapy (1. excluded from the functional dyspepsia umbrella. early satiety. cause of chronic symptoms needs an appropriate. or distinguishing organic from based clinical evaluation. A wait-and-see strategy of patient . Dyspepsia patients tolerate lower volumes than controls Several other alarm features have been traditionally ap- for example. anemia. progressive dyspha- cutoffs vary by laboratory (as do test protocols). Others have failed to demon. and in older There is convincing evidence that a patients symptoms cannot patients >55 yr of age with new symptoms. The physician also needs to de- empirical therapy is not currently recommended in individ. It is reasonable that the physician identify tional dyspepsia. lymphadenopathy. In patients with alarm features. Guidelines for the Management of Dyspepsia 2327 New clinical tests of gastric function are under evaluation. This in turn depends on Grade of evidence: C the underlying provisional diagnosis. anorexia. bleeding. and The patient who presents with new onset dyspepsia or be- scoring systems have all failed to be useful in identifying un. 41). However. and address such issues as fear of cancer or underlying heart disease in order to optimize management (52). full. gastroduodenal hypersensitivity. especially malignancy.

. randomized 500 patients (including The rationale for noninvasive H. are H. pylori-positive patients to omeprazole plus antibiotics or Conversely. Uninvestigated Dyspepsia in Primary Care prevalence populations in the United States (e. pylori Versus Prompt EGD in Primary ession: A and Secondary Care Grade of evidence for a H. high socioe. Cost-effectiveness stud- tomatic relapse after ceasing medication. in a study in primary care in the United States on stopping antisecretory therapy. Here. For example. 1). an alternative strategy is to including some GERD patients in this trial. H2 -blockers. or apply empiric empirically in those with the infection in the community antisecretory therapy after H. H. in an attempt to eradicate the infection. tive had a DU in 2% and GU in 3% (56). tial empirical treatment with a PPI is preferable (59). Others ommended around the world (54. although quality of life was unchanged. with 1. pylori infection plied in practice (44). pylori-negative patients are treated with empiric antisecretory therapy ini. pylori Versus Usual Management of should be based on the practice setting (Fig. in communities where gastric or esophageal omeprazole plus placebo for 1 wk. 58). ini- and-treat as the initial strategy. McColl that there were no differences in symptomatic outcomes or et al. in patients with peptic ulcer disease is less than 48%. Other studies suggest sidered. or PPIs and reevaluation can be con. the decision to endoscope or not a difference between test-and-treat and usual care (64). conducted a randomized placebo-controlled trial immigrants from developing countries) should undergo in 36 family practices in Canada. those who were breath test nega- antacids. particularly in primary care.329 for all patients with dyspepsia. pylori Versus Placebo in Dyspepsia in tially. pylori infection decreases below without alarm features are tested for H. The best option remains un. incidence of peptic ulcer (57. Another strategy worth that between 20% and 60% of patients with dyspepsia who considering is prescription of empirical full-dose or high. where the background prevalence of ulcer months. An underpowered U. they randomized 294 test-and-treat as the preferable nonendoscopic strategy. Empiric antisecre. compared to 36% in the placebo-therapy arm at the end of 12 conomic areas. recent Chiba et al. It is of interest that this benefit was observed despite or H. pylori The application of a test-and-treat strategy for H. TEST-AND-TREAT H. pylori infected will have underlying peptic ulcer dis- dose antisecretory therapy. If 20%.g. Test-and-Treat H.2328 Talley et al. H. were positive for H. pylori infection. pylori infection in patients with functional dyspepsia is the American College of Physicians and is still widely ap. Presumably much of this benefit is explained by the treatment of undiagnosed peptic ulcer disease. They found Scotland where the incidence of peptic ulcer is high. then the test-and-treat observed no cost benefit of test-and-treat over usual care al- strategy is best applied before consideration of referral for though symptoms were significantly reduced in the test-and- EGD. They found eradi- considered early but this would not apply to most of the cation resulted in no or minimal symptoms in 50% of patients country. EGD is not mandatory in those who remain symp. ies in the United States suggest that when the prevalence of tory therapy was the backbone of the guideline proposed by H. pylori test-and-treat strategy the Community is to either prescribe empiric antisecretory therapy first and There are data indicating a small benefit for treating H. pylori Test-and-Treat H. Lassen et al. The eradication prescribe first a course of antisecretory therapy empirically therapy arm also reduced costs by Can$53 per patient. must be based on clinical judgement. In low-prevalence populations (e. Grade of evidence for test-and-treat or acid suppr. Test-and-Treat H. reserving further evaluation for ease. older patients) in primary care with dyspepsia to either H. A third approach applies H.455 attended and were eligible. was an absolute risk reduction of 5% for upper GI symptoms on active therapy versus placebo. currently most widely rec. young patients have suggested that when H. A modification of the H.773 (76%) returning at 2 yr (61). (nonpatients). If the patient fails to respond or relapses rapidly lison et al. pylori reserve H. although the en- C13 urea breath test had a duodenal ulcer (DU) in 40% and doscopy group had a slightly higher patient satisfaction score . pylori test. study failed to detect tomatic as the yield is low. treat arm (63). High. less than 12% or when the prevalence of H.S. and then arranged follow- cancer has a high incidence. empiric antibiotic therapy is prescribed uninvestigated dyspepsia (60). pylori prevalence of less than There is consistent empiric evidence that a test-and-treat strat- 10% in the local community as the cutoff for deciding to egy is at least equivalent to prompt endoscopy in terms of use empiric acid suppression rather than test-and-treat: C outcomes. in pylori test-and-treat or prompt endoscopy (65). but this varies widely depending upon the background those who are either unresponsive or have an early symp. pylori and were assigned active treatment der debate. empiric PPI therapy starts to dominate test-and-treat in H. pylori eradication fails to re. pylori is detected. showed that in patients with dyspepsia and a positive quality of life between the groups at 1 yr.K. community trial.929 individu- lieve symptoms. but new data are available to help guide a rational or placebo. with use of over-the-counter gastric ulcer (GU) in 13%.. prompt endoscopy should be up by family physicians for usual care (62). In a U. 32. reassurance and education. pylori infection is low). tification of underlying peptic ulcer disease.g. Al- for 4–8 wk. pylori testing later for failures. A final approach is to perform prompt EGD als were invited and 8. pylori testing is the iden. 55). 2. There decision.

Antibiotic allergies and super-infection can occur. evaluated 232 icylate [Pepto Bismol
] 525 mg QID + metronidazole 250 patients in primary care. evaluated 708 patients under age 55 yr referred mg twice daily) administered for 7–10 days (7-day therapy for endoscopy. pylori eradication. They The current treatment of choice for H. pylori testing with lansoprazole. pylori therapy or immediate EGD. However. and tetracycline (Bismuth subsal- of life was similar in both groups. Guidelines for the Management of Dyspepsia 2329 of questionable clinical significance. When H. The urea breath test quality of life as well as a 48% reduction in the use of PPIs. eval. 10-day therapy is approved pylori test-and-treat or endoscopy including H. these patients were randomized to either H. Disadvantages of Test-and-Treat PROMPT ENDOSCOPY A notable disadvantage of test-and-treat is that cure of H. to either empiric H. is approved with rabeprazole. Hence. 79). Metronidazole (400 mg twice daily) may be substi- at the 12 months follow-up in the two groups. A total of 422 patients were randomly assigned to The choice of the H. pylori infection. 86). pylori infection will only lead to a minority reporting symp. unless convincing data to the contrary arise. for all patients requiring long-term acid suppression. only present in those with a predisposition to GERD who analysis (70) suggest overall that prompt EGD and test-and. 91 who had previously undergone for 14 days (80. of whom 141 underwent testing and mg QID + tetracycline 500 mg QID) combined with a PPI treatment for H. choice. Although not A final issue relates to potential complications of therapy. An alternative strategy is the combination of underwent endoscopy. least in this U. pylori infected pa- found that more patients became symptom free in the H. a positive test is more likely to be a tified a reduction in the number of endoscopic procedures false positive. endoscopy leads to improved patient satisfaction scores in . pylori test is critical.K. still depends on the positive in older people in the U. in Ireland a negative result is more likely to be a false negative (77). Where H. the results are difficult to interpret.S. metronidazole. and stool antigen test are currently the most accurate nonin. The cost-effectiveness of endoscopy local evaluated test is applied. pylori infection does not relieve initial endoscopy compared with usual management in pa- symptoms in all patients with peptic ulcer disease. pylori infection is highly prevalent. pylori gastritis may occur on acid suppression. and negative predictive value. pylori-positive patients and those have suggested H. pylori. they identified similar clini. 90 were seropositive for H. Seventy of these patients were H. Heaney et al. Patel et al. pylori infection increases 1 yr. which in turn is related to the There is only limited and unconvincing evidence that background prevalence of H. 81). Patients here were randomized serological tests in the United States (78. Jones et al. endoscopy in older patients that this is the strategy of first ever. the risk of development of reflux esophagitis or reflux symp- secutive controlled study. initial endoscopy in older patients with dyspepsia at vasive diagnostic tools and can be used with confidence (75. endoscopy and targeted medical therapy does no better. also have severe gastritis in the body or fundus that impairs treat have similar efficacy. pylori-positive urea breath test that detect active infection are preferable to on noninvasive testing (66). the H. py. a randomized controlled trial. even if a the cost of EGD was low. setting needs investigation. Hence. tients is a combination of PPI (standard dose twice daily) pylori eradication arm than in the prompt endoscopy arm. antibiotic resistance. Because this was a retrospective. 83). toms (82. pylori testing this is likely to be uncommon in most of the United States may provide adequate patient reassurance. The value of noninvasive H. pylori eradication should be considered with alarm features underwent prompt endoscopy. An unresolved issue is whether groups in follow up after referral back to their primary care test-and-treat will widen the problem of community acquired physician. and this can be confusing to the clinician (60–65). acid secretion. which ference in outcome or satisfaction was detected between the seems reasonable (85. this issue while much discussed should not be uated 193 dyspepsia patients under the age of 45 yr (71). with amoxicillin (1 g twice daily) and clarithromycin (500 McColl et al. Progression of out alarm features. evaluated the cost-effectiveness of an Indeed. endoscopy comprised the control group (68). as demonstrated in the above management There is empiric evidence from a management trial of prompt trials. unmatched noncon. eradication of H. and esomepra- (67). and some had alarm features. (84). No dif. Furthermore. either usual care or initial endoscopy. Many serologi. evaluated dyspepsia patients less than 45 yr old referred to Cost-effectiveness studies suggest that the stool test and the an open-access endoscopy unit who were H. Delaney et al. The authors also iden. pantoprazole. omeprazole. overall patient satisfaction and quality Bismuth. it appears likely that this risk is Additional randomized trial data (69) and a Cochrane meta. pylori and 23 H. performed in the test-and-treat arm. pylori testing. care (87). with at tients with dyspepsia over the age of 50 presenting in primary least one third continuing to be symptomatic (72. and have suboptimal arm showed significant improvement in symptom scores and sensitivity and specificity in practice (74). the initial endoscopy cal tests have not been locally validated. 73). It is con- cal outcomes but lower costs in the test-and-treat group at troversial whether eradication of H. They found no significant difference in dyspepsia score zole). study was potentially cost-effective provided 76). Advantages of Prompt Endoscopy tom improvement. How. a major clinical concern when contemplating test-and-treat. lori is very uncommon. Other evidence supports the view that H. pylori-seronegative with. which is reversed with H. tuted for amoxicillin in this regimen if the patient is allergic only 8% of patients who had testing and treatment eventually to penicillin.

efficacy and was inferior to acid suppression (101). endoscopy (44). although this may be worth considering in some demonstrated that consultations for dyspepsia fell by 57% patients. those who relapsed after therapy or those who failed of patients referred for open-access endoscopy for dyspepsia to respond to therapy in 7–10 days were to be referred for in the United States had high levels of health related anxiety. Endoscopy is invasive and although the risks of apparent short-term benefits of empiric therapy in these this procedure in relatively healthy patients are very low. it is rea- ased by patient and physician expectation that endoscopy is sonable to step up therapy. or both. They found there was significant improvement in satisfaction scores at one month after en. showed significant improvement after endoscopy. the United States. If initial acid suppression fails after 2–4 wk. par. The widespread availability of PPIs has re- following a normal endoscopy or the demonstration of mi. conducted a randomized trial com. conducted a trial in primary care of all patients would be very costly and would overwhelm en. and the ef. There have been improves patient outcome in dyspepsia compared with other no trials of metoclopramide. 1). issue of the risk-benefit ratio needs careful weighing. it is recom- and are more likely to be concerned about underlying cancer mended that treatment be stopped after 4–8 wk and if symp- (92). another course of the same treatment is justified. More- lized in this study (96). A systematic review concluded that over. this unblinded study may have been bi. pylori-serology that a general recommendation to perform endoscopies on (99). disease and did not exclude peptic ulcer. pylori-negative in 326 primary care patients with dyspepsia. an empiric strategy may be efficacious in uninvestigated dys- expected structural cause in a young patient with no alarm pepsia. Bytzer el al. 95). However. In the absence of established prokinetic drugs for with dyspepsia are reassured by EGD and may require fewer dyspepsia in the United States. A meta-analysis of several large studies has demonstrated fects were preserved for 6 months (86). this may require changing drug class or not considered. Health anxiety has been shown to lead to a cycle of toms recur. although the duration of reassurance is not es. this drug class is not cur- prescriptions. eventually underwent endoscopy during the 12 months of Grade of evidence: A follow-up. It is unknown doscopy for all dyspeptic patients that need to be carefully whether GERD or ulcer disease. and reassurance by the endoscopist. EMPIRIC ANTISECRETORY THERAPY IN UNINVESTIGATED paring prompt endoscopy with empiric H2 -receptive blocker DYSPEPSIA therapy in dyspepsia (88).2330 Talley et al. accounts for the considered. Hungin et al. dyspepsia. the most likely structural ab. an empiric trial of acid suppression In addition. Finding esophagitis. endoscopy was dyspepsia from Canada demonstrated that cisapride had low not superior to any of the empirical treatment strategies uti. tegaserod or domperidone in the empiric strategies (97). these stud- Disadvantages of Endoscopy ies frequently included patients with symptomatic reflux There are several potential disadvantages of prompt en. Furthermore. pylori status was pert opinion only. may often not lead to a change in management ized to receive cisapride as compared to placebo in the setting (94. in patients with normal endoscopy and by 37% in patients Grade of evidence: C with minor abnormalities at endoscopy. Quadri and Vakil demonstrated that one third wk. the high prevalence of dyspepsia means of uninvestigated dyspepsia and negative H. management of uninvestigated dyspepsia. repeated medical consultations. . scales initial empiric therapy in uninvestigated dyspepsia in place for preoccupation with health and fear of illness and death of H2 receptor antagonists (98). medication use was terminated or mended an empiric trial of an H2 receptor antagonist for 6–8 decreased (93). Quartero et al. it is contentious that prompt treatment success was similar in both groups but was un- EGD provides any direct benefits despite some positive stud. One study evaluated management strategies both drugs (100). 66% of the patients in the empiric therapy arm for 4–8 wk is recommended first-line therapy (Fig. Kearney et al. and H. and the relapse-free periods were also similar with ies quoted above. Dyspeptic patients who seek medical attention are more Grade of evidence: C concerned about the possible seriousness of their symptoms In patients who do respond to initial therapy. pylori-negative cases with uninvestigated dyspepsia doscopy compared to the empiric antisecretory therapy arm. severity of dyspeptic symptoms among 60 patients random- normality. sulted in this class of agents frequently being prescribed as nor abnormalities. alginate. Moreover. noted no significant difference in the features. der 50%. condition. In H. doscopy services. or placebo in primary care provides better symptomatic outcomes (70). Other studies have suggested that patients dosing. There are limited data that prokinetic therapy employed as ticularly as the procedure is very unlikely to identify an un. the reports. 563 patients who were randomized to ranitidine or cisapride. A randomized trial in H. In 60% of patients The American College of Physicians in 1985 recom- with normal endoscopy. although this is based on ex- the preferred management strategy. cisapride is no longer available because of rare toxicity most data failed to support the view that endoscopy alone from QTC prolongation and sudden death. a short course of PPI therapy compared with a H2 -receptor antagonist. and no alarm features. rently recommended as first-line therapy for dyspepsia in tablished (89–91). In a study of primary care There are no data on long-term self-directed therapy in this patients undergoing open-access endoscopy. However.

treatment versus empiric PPI therapy. then a noninvasive strategy based on serological testing became cost-effective (105). Bismuth. supporting test-and. This analysis was confined to patients notherapy. confirmed their results. simethicone. They found that an initial pared to empirical acid suppression was equivalent or not strategy of H. pylori. included broad groups of patients including those with obvi- ous reflux disease. reconsidered.S. Ofman et al. but these data suggest that in H. PPIs were significantly more effective than both positive dyspeptic patients. In Simethicone: B . Dietary therapy has no established efficacy treat (106). the most costly approach was test-and-treat fol- include the concern that peptic ulcer disease will be inappro. recommendations for piric antisecretory therapy may lead to long-term inappropri. pylori eradication fails. tested four different management strategies in to be of benefit over placebo in functional dyspepsia. and cognitive-behavioral ther- younger than 45 yr of age presenting in primary care. sucralfate. vestigated dyspepsia (60). They apy are supported by limited studies but cannot be generally identified initial antisecretory therapy followed by endoscopy recommended at the present time. A recent systematic review and economic analysis using generic/over-the-counter costs for PPIs found that they were H. as the least costly therapy per patient treated. Hyp- decision analysis (59). More lished papers that had 20 comparisons included. Antisecretory therapy can also lead to population. empiric PPI therapy is not the H2 receptor antagonists and antacids in uninvestigated dys- management option of choice in areas where the prevalence pepsia. However. pylori another U. The management of endoscopy-proven functional dyspep- verstein el al. Therefore. Ladabaum et al. compared test-and-treat with PPI therapy for a month with 12 months of follow-up in a secondary care setting in Italy (103). It prevalence of H. which in turn impacts on its potential of a H. In the WEIGHING THE OPTIONS test-and-treat arm. In a pooled studies are needed. but most (88%) were infected with H. pylori test-and-treat in There are only very limited data comparing empiric H. pylori test-and-treat compared with other strategies. the cost of endoscopy would need to drop from to support the use of herbal preparations. the test-and-treat strategy may need to be modified when the ate maintenance therapy that the patient does not require. This model also suggested priately and inadequately treated. There was insufficient data to determine ECONOMIC MODELS OF DYSPEPSIA MANAGEMENT whether empiric prokinetic therapy was beneficial. Em. 56% were eventually endoscoped because of poor symptom control. pylori test-and-treat strategy may be as effec- Fendrick et al. psychotherapy. but it was unclear whether test-and-treat com- uninvestigated dyspepsia (104). Sonnenberg ENDOSCOPY-NEGATIVE DYSPEPSIA (FUNCTIONAL noted that if the ulcer disease prevalence rate exceeded 10% DYSPEPSIA. pylori infection was 12% or less in the dyspeptic the therapy is ceased. pylori (and ulcer disease) decreases below 20%. NONULCER DYSPEPSIA) in H. concluded that there was a toss up between sia is particularly challenging when initial antisecretory H. and we recommend is unclear whether antisecretory therapy postpones eventual on the basis of expert opinion considering a PPI in the setting investigation or not. and $740 by 96% for an initial endoscopy strategy to become low-dose tricyclic antidepressants in functional dyspepsia. Upper GI radiology was not a cost-effective alternative to H. The impact piric PPI therapy starts to dominate test-and-treat in unin- of acid rebound in dyspepsia remains unclear (102). Guidelines for the Management of Dyspepsia 2331 Obvious disadvantages of empiric antisecretory therapy this model. tive as endoscopy-based management with reduced costs be- ment strategies in patient with suspected peptic ulcer disease. lowed by endoscopy for failures. equally cost-effective in their model (107). undertook economic modeling of manage. pylori prevalence below 10% in the local commu- cost-effectiveness. observed that as the likelihood misdiagnosis of peptic ulcer disease at subsequent endoscopy. Patients who fail reevaluation of this model applying the assumptions made by to respond to simple measures need to have their diagnosis Fendrick et al. pylori TEST-AND-TREAT VERSUS EMPIRIC cost-effective in the United States provided generic costs of a ANTISECRETORY THERAPY PPI were used in the analysis (108). cause of the decreased numbers of patients that subsequently which presumably applies to the majority of patients with require EGD. and patients subsequently that empirical PPI therapy became cost-effective if the preva- may present with complicated ulcer disease if for any reason lence of H. pylori-infected subjects. this Grades of evidence: rendered fewer patients symptom-free at 1 yr than strategies Dietary modification: C which combined empiric PPI therapy with test-and-treat. 88% were endoscoped and 17% had a peptic ment strategies for dyspepsia (70). but therapy and H. but none had a peptic ulcer. pylori. nity. analysis. in A Cochrane review has been conducted of available manage- the PPI arm. pylori infection is low. pylori is high. They identified 18 pub- ulcer. pylori testing and treatment was cost-effective. A significant limitation of the studies is that they of H. They also concluded a H. of H. em- as the ulcer will more likely heal and be missed. because of the lack of data. There are very limited data cost-saving. and antispasmodics are not established Spiegel et al. concluded that test-and-treat was but may help some individuals. Manes et al. Sil. model (109). unless the cost of endoscopy fell to less than $500 when prompt endoscopy became more cost-effective.

metoclopramide. Potential precip. ficacy. the proportion of patients dyspepsia.g. Food intolerance is the studies were with cisapride (98).2332 Talley et al. dition have been questioned. An increased tolerance to aver- ported significant benefit with lansoprazole in a U. pylori eradication therapy to infected pa- FUNCTIONAL DYSPEPSIA tients with functional dyspepsia. clonidine. with the number needed to therapy: B treat being 15 (118). PPIs in this review also produced a dysmotility-like dyspepsia (e. Large trials have failed to identify any difference in data are needed in larger patient populations before these can therapeutic outcome in H. Eradication of H. pylori erad. sumatriptan. The benefit of other treatments remains uncertain. Moreover. A Cochrane review of 8 provement (31. Prokinetics further correction of faulty ideas and provides reassurance should be reserved for difficult cases as options in the United that can be very helpful in long-term management. although Blum et al. but small studies have suggested benefit. Routine use of gas- ever. 122). 2 patients in the patient with long-standing symptoms has presented on this H. the diagnosis.. It is there. respectively.. it is accept- able to offer H. eating frequent and smaller meals prising 829 patients and showed that there was a relative throughout the day can sometimes be helpful. did identify a superior response tive therapies such as herbal preparations remain of unproven to PPI therapy in H. pylori-positive versus negative pa. Hsu et al. Specific foods risk reduction of 50%. compared with placebo. Psychotherapy. how- achieving complete relief of dyspepsia with lansoprazole 30 ever. nitric oxide donors) may theoretically improve some was generally poor (98). ing evidence is not available. Psychological outcome of acid suppression therapy in functional dyspepsia therapies are promising. but most of that precipitate symptoms can be avoided. but more (108). pylori status is unlikely to affect the therapeutic effect. Ascertaining why a ing 161 patients with functional dyspepsia.. popula. There are insufficient data on the United States (108). in gastric emptying do not correlate well with symptom im- alence with cisapride (110. H. States are few and current agents (e. However. sive visceral sensations may play a role in the therapeutic tion (113). analysis of uncommon. buspirone. although convinc- after they have had reassurance and education. the beneficial effect of low-dose amitryptyline seen in and 60 mg was 23% and 23%. one 5-yr study suggests any benefit MANAGEMENT OF DOCUMENTED will persist (119). pylori eradication therapy empirically to those negative endoscopy. Antidepres- of the trials was better (98). An economic model suggested sants are also of uncertain efficacy in functional dyspepsia but that PPI therapy was cost-effective for functional dyspepsia in are often prescribed (121. 124). as this may identify those in the placebo group (8%) developed peptic ulcers at repeat who have fears of an underlying serious disease or specific endoscopy (120). tegaserod) have limited or poorly established ef- functional dyspepsia based on a Cochrane review (98). trials of H2 receptor antagonists with 1. pylori-positive patients (114. Cognitive-behavioral ication in functional dyspepsia.S. pylori eradication in those with documented functional Many patients do not require medication for dyspepsia dyspepsia may help prevent ulcer disease.g. observed during 1 fore important for the clinician to explain the meaning of yr of follow-up in a randomized controlled trial compris- the symptoms and their benign nature. A itating factors in dyspepsia remain poorly defined. or side-effects are common (121). cisapride. it is worth reevaluating but significant therapeutic gain achieved with H. pylori eradication treatment group (3%) and 6 patients occasion for care can be helpful. While longer than 1-yr follow-up data are generally lacking. There are limited data with the SSRIs. 117). is reasonable even if ulcer disease is unlikely. particularly hypnotherapy. be recommended for routine use (126. psychological distress that can be addressed. 129). pylori in functional dyspepsia is contro- versial. How. 115). an empiric trial of therapy is commonly with otherwise uninvestigated dyspepsia who are infected prescribed. early satiety) but adequate relative risk reduction of approximately 30% and the quality randomized controlled trials are lacking (123). 111). and in another study equiv. The results also imply that Once a diagnosis of functional dyspepsia is confirmed by a offering H. However. compared with functional dyspepsia was not related to changes in perception 30% on placebo (112). value (128. In contrast. the benefits of all therapies in this con. On the basis of the evidence. 127). Other alterna- tients. a recent trial of simethicone has suggested potential tric emptying studies is not recommended as improvements benefit compared with placebo.125 patients showed tegaserod. Moreover. High-fat Cochrane review included 12 trials with prokinetics com- meals should be avoided.g. there is a small In patients with resistant symptoms. H. . Updating these meta-analyses now suggests that when all appropriate trials are considered. some a relative risk reduction of 30% but the quality of the trials SSRIs. Two high-quality meta-analyses have reached differ- ent conclusions but this may be likely explained by which ADDITIONAL DIAGNOSES AND TESTING trials were included and excluded in each systematic review IN REFRACTORY CASES (116. however. Drugs that relax the gastric fundus (e. Follow-up the studies suggested that publication bias at least partly ex- of the patient helps determine the natural history and allows plains the apparent benefits of prokinetic therapy. in a recent randomized trial the use of tricyclic antidepressants such as amitryptyline in of 453 patients from Hong Kong. Hypnotherapy. another recent trial re. of gastric distension (125). ery- Antacids and sucralfate were not superior to placebo in thromycin. and food allergy very rare.

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