J Gastroenterol 2008; 43:251255

DOI 10.1007/s00535-008-2167-8

Review
Functional dyspepsia: past, present, and future
BRECHT GEERAERTS and JAN TACK
Center for Gastroenterological Research K.U. Leuven, 49 Herestraat, 3000 Leuven, Belgium

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by symptoms originating from the gastroduodenal region in the absence of
underlying organic disease that readily explains the
symptoms. The Rome II consensus, which defined FD
as the presence of unexplained pain or discomfort in the
epigastrium, had a number of drawbacks, including an
unjustified focus on pain, inclusion of a large number
of nonspecific symptoms, and an unclear position on
overlap with gastroesophageal reflux disease (GERD)
and irritable bowel syndrome (IBS). The Rome III consensus redefined FD as the presence of epigastric pain
or burning, postprandial fullness or early satiation in the
absence of underlying organic disease. Frequent overlap
with GERD and IBS is acknowledged but does not
exclude a diagnosis of FD. A subgroup classification
into postprandial distress syndrome and epigastric pain
syndrome was proposed. Ongoing studies will clarify
the impact of this subdivision on clinical management
and treatment outcomes.
Key words: Rome III consensus, postprandial distress
syndrome (PDS), epigastric pain syndrome (EPS), postprandial fullness, early satiation

Introduction
In up to half of patients seen by gastroenterologists,
a standard work-up, which may include endoscopy,
laboratory testing, and radiological evaluation, fails to
provide an explanation for the patients symptoms.
This group of patients is referred to as patients with
functional gastrointestinal disorders (FGIDs), as it is

Received / Accepted: January 21, 2008

Reprint requests to: J. Tack

assumed that abnormalities of gastrointestinal function

underlie the generation of their symptoms. According
to the Rome consensus process, FGIDs in adults are
subdivided into six major domains, according to the
area of the gastrointestinal tract where symptoms are
thought to originate.1
Functional dyspepsia (FD), a functional syndrome
thought to originate in the gastroduodenal region, is
one of the most prevalent FGIDs. Over the last 20
years, the definition of FD has undergone major changes
from the 1988 working party definition of dyspepsia, to
the consecutive Rome I, Rome II, and most recently
Rome III definitions,26 in line with changing understanding of the categorization and the pathophysiological basis of this disorder.

Rome I and II definitions

According to the Rome I and Rome II definitions, FD
was defined as the presence of pain or discomfort centered in the upper abdomen, in the absence of organic
disease that readily explained the symptoms.4,5 While
the meaning of pain is readily understood, the notion of
discomfort is more difficult to grasp. It has remained
unsettled whether discomfort is a mild variant of pain
or a separate symptom complex.7 Moreover, discomfort
comprises a number of different nonpainful symptoms,
including upper abdominal fullness, early satiety, bloating, nausea, epigastric burning, belching, and vomiting.
While Rome I included some reflux symptoms with FD,
and recognized a subgroup of reflux-like dyspepsia (see
below), the Rome II definition of FD excluded patients
with predominant heartburn.4,5 The Rome II definition
also excluded irritable bowel syndrome (IBS) as a cause
of the symptoms by adding the requirement of no evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool
frequency or stool form.

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B. Geeraerts and J. Tack: Functional dyspepsia

Subgroups of functional dyspepsia according to

Rome I and II
Several working teams, including the Rome I and Rome
II consensus groups, considered FD a heterogeneous
condition that could be subdivided into symptom
subgroups, although the names and definitions have
varied.26 On the basis of symptom clusters, the Rome
I consensus identified subgroups of ulcer-like and dysmotility-like dyspepsia.4 The Rome II consensus identified the same subgroups based on the predominant
symptom being pain or discomfort.5
Previous working parties had also recognized a reflux-like subgroup of FD,2,3 but the Rome I consensus
proposed that these patients be considered to have gastroesophageal reflux disease (GERD) until proven otherwise, and this was maintained in the Rome II
consensus.4,5

present in all patients with FD, and there is considerable

variation in the symptom pattern among patients. The
Rome III committee therefore proposed to decrease
the number of FD symptoms to four specific symptoms
(postprandial fullness, early satiation, epigastric pain,
and epigastric burning) thought to originate from the
gastroduodenal region (Table 1). While other symptoms may coexist, they are not considered cardinal FD
symptoms as they may arise from other areas of the
gastrointestinal tract or the body. Bloating, for instance,
may be derived from the bowel, as it often occurs in IBS
or in functional bloating, so this was not considered
a cardinal symptom of dyspepsia. Similarly, nausea is
often of central origin, and together with vomiting is
also not considered a localizing symptom. Belching and
heartburn are considered esophageal rather than gastroduodenal symptoms.

Rationale for new subclasses of functional dyspepsia

Rationale for a new definition of functional dyspepsia
In the Rome II definition of FD, epigastric pain was
considered a key feature of FD, and seven other symptoms were grouped under the term discomfort.
Besides the lack of a clearly defined distinction between
pain and intense discomfort, analyses of the symptom
pattern do not support singling out pain over all other
symptoms.8 In fact, there is no single symptom that is

The Rome II definitions proposed a subclassification of

FD based on the predominant symptom.5 However,
subsequent research has shown that identification of the
predominant symptom lacks stability over a short time
period.8,9 Nevertheless, there is increasing evidence of
heterogeneity of FD based on factor analyses in the
general population and in referral populations (Table
2). These analyses have failed to support the existence

Table 1. Dyspeptic symptoms according to the Rome III consensus

Epigastric pain

Postprandial fullness
Early satiation

Epigastric burning

Epigastric refers to the region between the umbilicus and lower end of the sternum, marked by
the midclavicular lines. Pain refers to a subjective, unpleasant sensation; some patients may feel
that tissue damage is occurring. Epigastric pain may or may not have a burning quality. Other
symptoms may be extremely bothersome without being interpreted by the patient as pain.
An unpleasant sensation like the prolonged persistence of food in the stomach.
A feeling that the stomach is overfilled soon after starting to eat, out of proportion to the size of
the meal being eaten, so that the meal cannot be finished. Previously, the term early satiety
was used, but satiation is the correct term for the disappearance of the sensation of appetite
during food ingestion.
Epigastric refers to the region between the umbilicus and the lower end of the sternum, marked
by the midclavicular lines. Burning refers to an unpleasant subjective sensation of heat.

Table 2. Evidence of heterogeneity of functional dyspepsia based on factor analyses in the general population and in
referral populations
Study
Westbrook 2002 (11)
Fischler 2003 (12)
Tack 2003 (13)
Jones 2003 (14)
Kwan 2003 (15)
Whitehead 2003 (16)
Camilleri 2005 (17)
Piessevaux 2008 (18)

Population

Factors

Population sample
Tertiary care
Tertiary care
Population sample
Tertiary care
Tertiary care
Population sample
Population sample

2300
438
638
888
1012
1041
21128
2025

3 dyspeptic symptom factors

4 dyspeptic symptom factors
3 dyspeptic symptom factors
3 dyspeptic symptom factors
3 dyspeptic symptom factors
4 dyspeptic symptom factors
3 dyspeptic symptom factors
3 or 4 dyspeptic symptom factors

B. Geeraerts and J. Tack: Functional dyspepsia

253

Functional Dyspepsia

Postprandial distress
syndrome (PDS):
Meal-related FD
- Early satiation
- Postprandial fullness

Epigastric pain
syndrome (EPS):
Meal-unrelated FD
- Epigastric pain
- Epigastric burning

of FD as a homogeneous condition.1118 Although there

are some differences between studies, symptom groupings are consistently found, and these include an epigastric pain factor, a factor of meal-induced symptoms,
including postprandial fullness or early satiation, and
a nausea factor (with or without vomiting). In some
studies, belching also appears as a separate fourth
symptom group.
By definition, certain symptoms such as early satiation or postprandial fullness are related to the ingestion
of a meal. All factor analysis studies identified a separate factor of meal-related symptoms. Systematic studies
revealed that symptoms are induced or worsened by
meal ingestion in the majority of patients with dyspeptic
symptoms, but there are patients in whom symptoms
are not related to ingestion of a meal.18,19 The Rome III
committee proposed a distinction between meal-induced
symptoms and meal-unrelated symptoms to be pathophysiologically and clinically relevant, and this distinction forms the basis of newly defined subcategories of
FD. FD is now further subdivided into two new diagnostic categories: (1) meal-induced dyspeptic symptoms
[postprandial distress syndrome (PDS)], characterized
by postprandial fullness and early satiation, and (2) epigastric pain syndrome (EPS), characterized by epigastric pain and burning (Fig. 1). It is likely that refinements
(e.g., distinctions between meal-related pain and interdigestive pain) may be necessary in the future, but such
refinements await further studies.

Overlap with gastroesophageal reflux disease and with

irritable bowel syndrome
The issue of overlap with GERD has been a difficult
topic. While earlier working parties considered a group
of reflux-like dyspepsia,2,3 the Rome committees consid-

Fig. 1. Rome III subgroups of functional

dyspepsia (FD)

ered this primarily a GERD group, and it was excluded

from FD.4,5 The Rome II definition excluded patients
with predominant heartburn from the FD spectrum,5
but additional studies have demonstrated that the predominant symptom approach does not reliably identify
all patients with GERD.2022
Furthermore, it is clear that there is not a uniform
interpretation of the implications of the guideline that
excludes predominant heartburn. On the one hand,
several large studies included heartburn and even acid
regurgitation as typical symptoms of dyspepsia.23,24
On the other hand, regulatory authorities often required
exclusion of all heartburn in FD therapeutic trials.
Whereas the Rome II definition of FD excluded patients
with predominant heartburn and was unclear on nonpredominant heartburn, the Rome III definition states
that heartburn is not a gastroduodenal symptom,
although it often occurs simultaneously with FD symptoms, and its presence does not exclude the diagnosis
of FD.6 Similarly, the frequently occurring overlap of
FD with IBS25 is explicitly recognized.6

Implications for patient management

The Rome III subdivision of FD was proposed under
the assumption that different underlying pathophysiological mechanisms would be present in each of the
subgroups and, consequently, that different treatment
modalities would be most suitable for each subgroup.
Acid suppression is a frequently used first-line
therapy, especially in the absence of Helicobacter pylori
infection. In the presence of H. pylori, eradication is
often proposed, but meta-analyses show that the yield
in terms of symptom relief is limited.26 A meta-analysis
of controlled, randomized trials with proton pump
inhibitors (PPIs) in FD reported that this class of agents

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B. Geeraerts and J. Tack: Functional dyspepsia

Dyspeptic symptoms
Endoscopy
70%

Functional dyspepsia

Organic dyspepsia

(eradicate if HP+)

Meal-related (PDS)

Meal-unrelated (EPS)

Prokinetic

Acid suppressive

Add or switch to
acid suppressive

Add or switch
to prokinetic

Tricyclic agent if refractory

was superior to placebo.27 However, much of this benefit

may be explained by unrecognized GERD. According
to this meta-analysis, epigastric pain, but not mealrelated symptoms, seems to respond to a PPI.27 Similarly, meta-analyses suggest that prokinetics may be
superior to placebo for so-called motility-like dyspepsia, but publication bias may also account at least in part
for some of the positive meta-analyses in the literature.28,29 Antidepressants are often used in refractory
cases, but the evidence for their efficacy is limited.30
Nevertheless, on the basis of the available pre-Rome
III literature, one might propose initial therapy with
a PPI in EPS, and with a prokinetic in PDS. In case
of refractoriness, combined therapy or a psychotropic
agent might be considered (Fig. 2). A priori H. pylori
eradication can be considered in all infected FD patients,
but the yield will be limited, and this is a subgroup that
is expected to become progressively smaller with time.
Investigating and proving the usefulness of such a management algorithm will be on the agenda for the near
future.

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Fig. 2. Possible treatment algorithm

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