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American Family Physician 547
Update on the Evaluation and Management
of Functional Dyspepsia
RYAN A. LOYD, MD, and DAVID A. McCLELLAN, MD, Texas A&M Health Science Center College
of Medicine, Bryan, Texas
patients who seek care are eventually diag-
nosed as functional dyspepsia.2 Functional
(nonulcer) dyspepsia is defined as the pres-
ence of postprandial fullness, early satiation,
or epigastric pain or burning in the absence
of causative structural disease (Table 1).3,4
Recent guidelines distinguish dyspep-
sia from heartburn and gastroesophageal
reflux symptoms, which often coincide with
dyspepsia but are considered separate enti-
ties.5 Previous studies have used a variety of
definitions for dyspepsia. As a result, fur-
ther research is needed to better differenti-
ate functional dyspepsia from other diseases
of the gastrointestinal (GI) tract. To facili-
tate this research, the Rome III diagnostic
yspepsia affects up to 40 percent
of adults each year, and about
10 percent of those affected seek
medical care.1 Most cases in
criteria divide functional dyspepsia into two
subcategories: epigastric pain syndrome (i.e.,
epigastric pain or burning) and postprandial
distress syndrome (i.e., postprandial full-
ness or early satiation).3
There is no definitive pathophysiologic
mechanism for functional dyspepsia, which
suggests that it is a heterogeneous group of
disorders. Patients with functional dyspepsia
commonly have coexisting symptoms of irri-
table bowel syndrome or other functional GI
disorders.6 In one 10-year follow-up study of
patients with dyspepsia or irritable bowel syn-
drome, 40 percent of symptomatic patients
switched subgroups over the study period.7
Several studies implicate gastric dysmotil-
ity in the pathophysiology of functional
dyspepsia.8-12 Many patients experience
Dyspepsia affects up to 40 percent of adults each year and is often diagnosed as functional (nonulcer) dyspepsia.
The defining symptoms are postprandial fullness, early satiation, or epigastric pain or burning in the absence of
causative structural disease. These symptoms may coexist with symptoms of functional gastrointestinal disorders,
such as gastroesophageal reflux and irritable bowel syndrome, as well as anxiety and depression. The history and
physical examination can help identify other possible causes of the symptoms. Warning signs of serious disease,
such as cancer, are unintended weight loss, progressive dysphagia, persistent vomiting, evidence of gastrointestinal
bleeding, and a family history of cancer. In these cases, more exten-
sive laboratory investigation, imaging, and endoscopy should be
considered as clinically indicated. During the initial evaluation, a
test-and-treat strategy to identify and eradicate Helicobacter pylori
infection is more effective than empiric treatment and more cost-
effective than initial endoscopy. Eradication of H. pylori helps one
out of 15 patients with functional dyspepsia diagnosed by endos-
copy, but may not be cost-effective. Treatment options that may be
beneficial for functional dyspepsia include histamine H2 blockers,
proton pump inhibitors, and prokinetic agents. Although psycho-
tropic medications and psychological interventions have no proven
benefit in patients with functional dyspepsia, they are appropriate
for treating common psychiatric comorbidities. (Am Fam Physi-
cian. 2011;83(5):547-552. Copyright © 2011 American Academy of
▲ Patient information:
A handout on dyspepsia,
written by the authors of
this article, is provided on
ILLUSTRATION BY ENID HATTON
Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2011 American Academy of Family Physicians. For the private, noncommercial
548 American Family Physician
Volume 83, Number 5 ◆ March 1, 2011
motility-related symptoms, such as bloating, early satia-
tion, nausea, and vomiting. Studies have documented
altered gastric motility (e.g., gastroparesis, gastric dys-
rhythmias, abnormal fundus accumulation, pyloric
sphincter dysfunction) in up to 80 percent of patients
with functional dyspepsia.8,9 However, the degree of dys-
motility does not correlate with symptoms.8-12
Because many patients with functional dyspepsia
have burning pain that is indistinguishable from ulcer-
related dyspepsia, the relationship between functional
dyspepsia and acid secretion is unclear. One study dem-
onstrated a lower pH level in the duodenum of patients
with functional dyspepsia compared with those in the
control group, although the pH level did not correlate
with symptoms.13 The role of Helicobacter pylori infec-
tion in functional dyspepsia has also been investigated.
Large population studies have shown an increased inci-
dence of H. pylori infection in patients with functional
dyspepsia; however, given the high incidence of both
conditions in the general population and the minimal
response to treatment, the significance of the association
is unclear.1,14 In spite of this uncertainty, testing for and
treating H. pylori infection have become integral to the
diagnostic management of functional dyspepsia.
Functional dyspepsia is a diagnosis of exclusion; there-
fore, physicians should focus on excluding serious or spe-
cifically treatable diseases, without spending too much
time investigating symptoms. Dyspepsia has a broad
and diverse differential diagnosis (Table 215-18), including
functional dyspepsia, peptic ulcer disease, reflux esopha-
gitis, and gastric or esophageal malignancy. Functional
dyspepsia is the most prevalent diagnosis, making up
70 percent of dyspepsia cases.15
The physician should perform a detailed history and
physical examination at the initial presentation, not-
ing any findings that point to a diagnosis other than
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Physicians should proceed directly to endoscopy in patients with dyspepsia
who have warning signs (e.g., unintended weight loss, progressive
dysphagia, persistent vomiting, evidence of gastrointestinal bleeding,
family history of cancer) or who are older than 55 years.
In patients with isolated dyspepsia who do not exhibit warning signs, a
test-and-treat strategy for Helicobacter pylori infection is effective and less
expensive than initial endoscopy.
Histamine H2 blockers and proton pump inhibitors reduce functional
dyspepsia symptoms, although the effect is small.
The prokinetic agent metoclopramide (Reglan) may be effective in treating
functional dyspepsia, although the data are limited.
Meta-analysisEradication of H. pylori is somewhat effective in reducing symptoms of
endoscopically confirmed functional dyspepsia, although it may not be
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.
Table 1. Rome III Diagnostic Criteria for
Presence of at least one of the following:
Bothersome postprandial fullness
No evidence of structural disease (including at upper
endoscopy) that is likely to explain the symptoms
NOTE: Criteria must be fulfilled for the past three months, with symp-
tom onset at least six months before diagnosis.
Information from references 3 and 4.
March 1, 2011 ◆ Volume 83, Number 5
American Family Physician 549
functional dyspepsia (e.g., right upper-quadrant pain
with cholelithiasis, exercise association with coronary
artery disease, radiation to the back with pancreatitis).
Table 3 includes medications and other agents com-
monly associated with dyspepsia.19 Because the differ-
ential diagnosis is broad, the workup can
range from empiric therapy to extensive
laboratory and imaging studies. Figure 1 is
an algorithm for the evaluation and treat-
ment of patients with dyspepsia.5,19
History and physical examination alone
have low sensitivity and specificity for pre-
dicting which patients with dyspepsia will
have organic disease discovered on esopha-
gogastroduodenoscopy.15,20 Because of this
inaccuracy, the high incidence of normal
endoscopic findings, and the very low inci-
dence of malignancy, it is desirable to try
empiric treatment before invasive and
expensive diagnostic testing.
Several strategies have been suggested
for initial management of uninvestigated
dyspepsia, including a trial of acid sup-
pressants, a test-and-treat approach (for
H. pylori infection), and early endoscopy.
A Cochrane review found that in the absence
of warning signs for serious disease, a test-
and-treat strategy is effective and cheaper
than initial endoscopy.21 Initial endoscopy
has been shown to provide a small reduction
in the risk of recurrent dyspepsia symptoms;
however, physicians need to weigh the cost
of endoscopy against patient preference for
early reassurance and symptom reduction.21
The Cochrane review showed the test-and-
treat strategy to be slightly more effective
than empiric acid suppressants, although the
comparative cost-effectiveness of these strat-
egies has not been established.21 Physicians
can diagnose H. pylori infection with non-
invasive tests, such as serologic, stool antigen,
or urea breath tests. Serologic testing is the
most common because of its wide availability
and low cost, although urea breath testing is
In patients 55 years or younger, the Amer-
ican Gastroenterological Association (AGA)
identifies several warning signs that should
trigger an early, aggressive workup (e.g.,
unintended weight loss, progressive dys-
phagia, persistent vomiting, evidence of GI
bleeding, family history of cancer).5 The AGA recom-
mends proceeding directly to endoscopy in patients with
warning signs and in those older than 55 years5; how-
ever, there has been debate about a lower cutoff age of
35 to 45 years in men.23 Although it is not addressed in
Table 2. Differential Diagnosis of Dyspepsia
Functional (nonulcer) dyspepsia
Peptic ulcer disease
Gastric or esophageal cancer
Abdominal cancer, especially pancreatic cancer
Biliary tract disease
Carbohydrate malabsorption (lactose, sorbitol,
Infiltrative diseases of the stomach (Crohn disease,
Intestinal parasites (Giardia species, Strongyloides
Ischemic bowel disease
Medication effects (Table 3)
Metabolic disturbances (hypercalcemia, hyperkalemia)
Systemic disorders (diabetes mellitus, thyroid and
parathyroid disorders, connective tissue disease)
Up to 70 percent
15 to 25 percent
5 to 15 percent
< 2 percent
*—Based on the occurrence of the disorders in patients with dyspepsia who are eval-
uated with endoscopy.
Information from references 15 through 18.
Table 3. Agents Commonly Associated with Dyspepsia
Antibiotics, oral (e.g., erythromycin)
Corticosteroids (e.g., prednisone)
Herbs (e.g., garlic, ginkgo,
saw palmetto, feverfew, chaste
tree berry, white willow)
Adapted from Dickerson LM, King DE. Evaluation and management of nonulcer dys-
pepsia. Am Fam Physician. 2004;70(1):109.
550 American Family Physician
Volume 83, Number 5 ◆ March 1, 2011
the AGA guidelines, an initial complete blood count may
be appropriate to screen for anemia. The AGA guide-
lines do not address laboratory testing and imaging;
however, it is reasonable to consider these approaches
in patients with negative esophagogastroduodenoscopy
findings and warning signs, or if the treatment course is
Treatment of functional dyspepsia can be frustrating for
physicians and patients because few treatment options
have proven effective. Patients will need continued reas-
surance and support from their physicians. Treatment is
generally aimed at one of the presumed underlying etiolo-
gies of functional dyspepsia.
GASTRIC ACID SUPPRESSION
Gastric acid suppressants have been stud-
ied extensively in the treatment of func-
tional dyspepsia. Although their benefit
in patients with ulcer-related dyspepsia or
gastroesophageal reflux disease is consid-
erable, the benefit in patients with func-
tional dyspepsia is less clear. Antacids,
sucralfate (Carafate), and misoprostol
(Cytotec) have been evaluated in limited
studies without evidence of benefit.24
Bismuth salts showed some benefit com-
pared with placebo in a meta-analysis;
however, the studies that showed benefit
were not well designed and involved only
patients with H. pylori infection, with
intent to eradicate the infection. Because
of the questionable benefit and long-term
risk of neurotoxicity, bismuth salts can-
not be recommended as first-line agents
for functional dyspepsia.24
Histamine H2 blockers are more prom-
ising agents for treating functional dys-
pepsia and have been evaluated in multiple
trials. A meta-analysis concluded that H2
blockers significantly improve symptoms;
however, there was evidence of some pub-
lication bias, and the effect may have been
overestimated, especially in comparison
with proton pump inhibitors.24 Studies
of proton pump inhibitors have shown a
statistically significant improvement in
symptoms of functional dyspepsia com-
pared with placebo. These studies were of
better quality than those investigating H2
blockers, making it difficult to compare
relative effectiveness.24 Given the small
benefit of gastric acid suppressants and
the commonly chronic nature of func-
tional dyspepsia symptoms, physicians
must consider the cost and long-term
safety profile of the medication chosen for
Evaluation and Management of Dyspepsia
*—Physicians may prefer a trial of antisecretory therapy before testing for H. pylori infec-
tion, especially when the onset of dyspepsia is relatively recent (less than three to six months)
Figure 1. Algorithm for the evaluation and management of dyspepsia.
Adapted from Dickerson LM, King DE. Evaluation and management of nonulcer dyspepsia. Am
Fam Physician. 2004;70(1):110, with additional information from reference 5.
Patient presents with
Exclude diagnoses with
history and physical
(see Table 2 for
Evaluate patient for serious risk factors:
age > 55 years,5 unintended weight
loss, progressive dysphagia, persistent
vomiting, evidence of gastrointestinal
bleeding, family history of cancer
Risk factors present No risk factors
Test for Helicobacter pylori
infection, and treat if present*
Positive for specific
diagnosis: treat as
Trial of antisecretory therapy
if patient is still symptomatic
Perform endoscopy Continue treatment with
Evaluate and treat comorbid conditions (e.g., stress, anxiety, depression)
Consider judicious use of laboratory tests and imaging when clinically indicated
March 1, 2011 ◆ Volume 83, Number 5
American Family Physician 551
Many patients with functional dyspepsia report pre-
dominant symptoms of bloating, early satiation, nausea,
and vomiting. As a result, physicians have tried targeting
treatment at improving GI motility. Multiple random-
ized controlled trials have demonstrated that prokinetic
agents are effective in treating functional dyspepsia.24
However, the quality of these studies is questionable,
and the effectiveness of the agents may have been over-
estimated. The trials showing effectiveness tended to be
targeted at patients with symptoms suggestive of motil-
ity disorders, raising the question of their effectiveness
in cases of isolated epigastric pain. Also, most studies
showing effectiveness used cisapride, which has since
been removed from the U.S. market because of con-
cerns about cardiac arrhythmias.24 One study has shown
that domperidone is effective for functional dyspep-
sia.24 Domperidone is relatively safe, but has not been
approved for use in the United States.
The only available prokinetic agents in the United
States are metoclopramide (Reglan) and erythromycin,
for which the evidence is sparse. Metoclopramide may
cause tardive dyskinesia and parkinsonian symptoms in
older persons, limiting its use.24 Erythromycin has some
prokinetic effects and is used to treat gastroparesis. How-
ever, erythromycin has not been studied as a treatment
for functional dyspepsia, so its effectiveness is unknown.
There is some initial evidence to suggest that herbal for-
mulations containing peppermint improve functional
dyspepsia symptoms, possibly through effects on the
smooth muscle of the intestines.25,26 However, pepper-
mint formulations available in the United States have not
been well studied, and more research is needed.
H. PYLORI ERADICATION
H. pylori eradication may be beneficial as an initial
strategy for management of uninvestigated dyspepsia
before endoscopy. Several meta-analyses have examined
eradication therapy in patients with endoscopically con-
firmed functional dyspepsia.19 Although there have been
some discrepancies between studies, the most recent
meta-analysis showed a small but statistically significant
improvement in functional dyspepsia symptoms with
H. pylori eradication.27 The number needed to treat for
one patient to have relief of symptoms is 15. It is not
known whether this strategy is cost-effective.22,27
PSYCHOTROPIC AND PSYCHOLOGICAL INTERVENTIONS
Because of the high rate of coexisting depression and
psychiatric illness in patients with refractory functional
dyspepsia, many physicians prescribe antidepressants.
However, there are only limited studies with a lack of
randomized controlled trials supporting this strategy.
A meta-analysis showed that tricyclic antidepressants
significantly improved functional GI disorders, but the
review did not isolate functional dyspepsia from other
functional GI disorders, such as irritable bowel syn-
drome and heartburn.28 A small crossover study found
that low-dose amitriptyline improved functional dyspep-
sia symptoms; however, it included only 14 patients and
lasted only one month.29 A larger study of children with
irritable bowel syndrome, functional abdominal pain,
or functional dyspepsia showed no improvement with
sus placebo.30 More
trials are underway
that may elucidate
the use of tricyclic
patients with func-
Four randomized controlled trials investigated the use
of psychological interventions in patients with dyspep-
sia symptoms.32 Because each trial evaluated a different
intervention (i.e., psychotherapy, psychodrama, cogni-
tive behavior therapy, relaxation therapy, and hypnosis),
no meta-analysis was possible. Additionally, because of
the poor quality of these trials, there was insufficient evi-
dence to recommend these interventions for treatment
of dyspepsia. However, these methods can still be used
to treat common psychiatric comorbidities.
Data Sources: A search was completed in PubMed and the Cochrane
Database of Systematic Reviews using the following keywords: nonulcer/
functional, nonulcer + dyspepsia ± cause, evaluation, treatment, and
Helicobacter pylori. Search date: April 1, 2010.
RYAN A. LOYD, MD, is an assistant professor of family and community
medicine, and director of global health for the Family Medicine Residency
at the Texas A&M Health Science Center College of Medicine in Bryan, Tex.
DAVID A. McCLELLAN, MD, is an assistant professor of family and commu-
nity medicine, and director of the Family Medicine Residency at the Texas
A&M Health Science Center College of Medicine.
Address correspondence to Ryan A. Loyd, MD, Texas A&M Health Sci-
ence Center College of Medicine, 1301 Memorial Dr., Ste. 200, Bryan, TX
77802 (e-mail: email@example.com). Reprints are not available
from the authors.
Author disclosure: Nothing to disclose.
1. McNamara DA, Buckley M, O’Morain CA. Nonulcer dyspepsia. Cur-
rent concepts and management. Gastroenterol Clin North Am.
There is a high rate of coex-
isting depression and psy-
chiatric illness in patients
with refractory functional
Functional Dyspepsia Download full-text
552 American Family Physician
Volume 83, Number 5 ◆ March 1, 2011
2. McQuaid K. Dyspepsia. In: Feldman M, Friedman LS, Sleisenger MH.
Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysi-
ology, Diagnosis, Management. 7th ed. Philadelphia, Pa.: Saunders;
3. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders
[published correction appears in Gastroenterology. 2006;131(1):336].
4. Drossman DA, Corazziari E, Delvaux M, et al. Rome III: The Functional
Gastrointestinal Disorders. 3rd ed. McLean, Va.: Degnon Associates;
898.pdf. Accessed June 15, 2010.
5. Talley NJ. American Gastroenterological Association medical position
statement: evaluation of dyspepsia. Gastroenterology. 2005;129(5):
6. Kaji M, Fujiwara Y, Shiba M, et al. Prevalence of overlaps between
GERD, FD and IBS and impact on health-related quality of life. J Gastro-
enterol Hepatol. 2010;25(6):1151-1156.
7. Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. Fluctuation of
gastrointestinal symptoms in the community: a 10-year longitudinal
follow-up study. Aliment Pharmacol Ther. 2008;28(8):1013-1020.
8. Sha W, Pasricha PJ, Chen JD. Correlations among electrogastrogram,
gastric dysmotility, and duodenal dysmotility in patients with functional
dyspepsia. J Clin Gastroenterol. 2009;43(8):716-722.
9. Sha W, Pasricha PJ, Chen JD. Rhythmic and spatial abnormalities of gas-
tric slow waves in patients with functional dyspepsia. J Clin Gastroen-
10. Mizushima T, Sawa K, Ochi K, et al. Gastrobiliary motility is not coor-
dinated in patients with non-ulcer dyspepsia of normal gastric emp-
tying time: simultaneous sonographic study. J Gastroenterol Hepatol.
11. Lin X, Levanon D, Chen JD. Impaired postprandial gastric slow waves in
patients with functional dyspepsia. Dig Dis Sci. 1998;43(8):1678-1684.
12. Lin Z, Eaker EY, Sarosiek I, McCallum RW. Gastric myoelectrical activity
and gastric emptying in patients with functional dyspepsia. Am J Gas-
13. Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in
patients with functional dyspepsia and controls using a radiotelemetry
pH monitoring system. J Clin Gastroenterol. 2009;43(6):527-533.
14. Armstrong D. Helicobacter pylori infection and dyspepsia. Scand J Gas-
troenterol Suppl. 1996;215:38-47.
15. Value of the unaided clinical diagnosis in dyspeptic patients in primary
care. Am J Gastroenterol. 2001;96(5):1417-1421.
16. Bazaldua OV, Schneider FD. Evaluation and management of dyspepsia.
Am Fam Physician. 1999;60(6):1773-1784.
17. Talley NJ, Silverstein MD, Agréus L, Nyrén O, Sonnenberg A, Holtmann G.
AGA technical review: evaluation of dyspepsia. American Gastroentero-
logical Association. Gastroenterology. 1998;114(3):582-595.
18. Fisher RS, Parkman HP. Management of nonulcer dyspepsia. N Engl
J Med. 1998;339(19):1376-1381.
19. Dickerson LM, King DE. Evaluation and management of nonulcer dys-
pepsia. Am Fam Physician. 2004;70(1):107-114.
20. Moayyedi P, Talley NJ, Fennerty MB, Vakil N. Can the clinical history
distinguish between organic and functional dyspepsia? JAMA. 2006;
21. Delaney B, Ford AC, Forman D, Moayyedi P, Qume M. Initial manage-
ment strategies for dyspepsia. Cochrane Database Syst Rev. 2005;(4):
22. Ables AZ, Simon I, Melton ER. Update on Helicobacter pylori treatment.
Am Fam Physician. 2007;75(3):351-358.
23. Marmo R, Rotondano G, Piscopo R, et al. Combination of age and sex
improves the ability to predict upper gastrointestinal malignancy in
patients with uncomplicated dyspepsia: a prospective multicentre data-
base study. Am J Gastroenterol. 2005;100(4):784-791.
24. Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D. Pharmaco-
logical interventions for non-ulcer dyspepsia. Cochrane Database Syst
25. Kligler B, Chaudhary S. Peppermint oil. Am Fam Physician. 2007;75(7):
26. Melzer J, Rösch W, Reichling J, Brignoli R, Saller R. Meta-analysis: phyto-
therapy of functional dyspepsia with the herbal drug preparation STW 5
(Iberogast). Aliment Pharmacol Ther. 2004;20(11-12):1279-1287.
27. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for
non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006;(2):CD002096.
28. Jackson JL, O’Malley PG, Tomkins G, Balden E, Santoro J, Kroenke K.
Treatment of functional gastrointestinal disorders with antidepressant
medications: a meta-analysis. Am J Med. 2000;108(1):65-72.
29. Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA. Effect of
amitriptyline on symptoms, sleep, and visceral perception in patients
with functional dyspepsia. Am J Gastroenterol. 1998;93(2):160-165.
30. Saps M, Youssef N, Miranda A, et al. Multicenter, randomized, placebo-
controlled trial of amitriptyline in children with functional gastrointesti-
nal disorders. Gastroenterology. 2009;137(4):1261-1269.
31. Talley NJ, Herrick L, Locke GR. Antidepressants in functional dyspepsia.
Expert Rev Gastroenterol Hepatol. 2010;4(1):5-8.
32. Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D. Psychologi-
cal interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev.