Dispepsia Functionala Utd

Functional dyspepsia
Page 1 of 15
Official reprint from UpToDate
www.uptodate.com 2013 UpToDate
Authors
George F Longstreth, MD
Brian E Lacy, MD, PhD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2013. | This topic last updated: Aug 29, 2013.
INTRODUCTIONDyspepsia is a common symptom with an extensive differential diagnosis and a
heterogeneous pathophysiology. It occurs in approximately 25 percent of the population each year, but
most affected people do not seek medical care.
Approximately 25 percent of patients with dyspepsia have an underlying organic cause. However, up to
75 percent of patients have functional (idiopathic or nonulcer) dyspepsia with no underlying cause
identified during diagnostic evaluation.
This topic review will provide an overview of the pathophysiology and treatment of functional dyspepsia.
The definition, etiology, and general approach to the evaluation and management of the patient with
dyspepsia are presented separately. (See "Approach to the patient with dyspepsia".)
The recommendations for the management of functional dyspepsia are largely consistent with the
American Gastroenterological Association guidelines [1].
DEFINITIONAccording to the Rome III criteria, functional dyspepsia is defined as the presence of one
or more of the following: postprandial fullness, early satiation, epigastric pain or burning and no evidence
of structural disease (including at upper endoscopy) to explain the symptoms [2]. While patients with
these symptoms and a negative diagnostic evaluation likely have functional dyspepsia, according to the
Rome III guidelines, the criteria should be fulfilled for the last three months with symptom onset at least
six months before diagnosis.
Functional dyspepsia is classified into postprandial distress syndrome and epigastric pain syndrome
(table 1) [1].
PATHOPHYSIOLOGYWhile several mechanisms have been proposed, the pathogenesis of functional
dyspepsia remains unclear [3].
Gastric motility and complianceSeveral motility disorders have been reported in patients with
dyspepsia. These include delayed gastric emptying, antral hypomotility, gastric dysrhythmias, and
impaired gastric accommodation in response to a meal [4-6].
However, these findings are noted in only a subset of patients with dyspepsia. As examples, delayed
gastric emptying and antral hypomotility are found in only 30 percent of patients with dyspepsia and up to
10 percent of patients with dyspepsia have rapid gastric emptying [7-10]. (See "Gastroparesis: Etiology,
clinical manifestations, and diagnosis".)
http://www.uptodate.com.ezproxy.umf.ro/contents/functional-dyspepsia?topicKey=GAST...
9/21/2013
Page 2 of 15
Visceral hypersensitivityVisceral hypersensitivity is characterized by a lowered threshold for

induction of pain in the presence of normal gastric compliance. Several studies have demonstrated
visceral hypersensitivity in patients with functional dyspepsia that occurs independently of delayed gastric
emptying [11-15]. Both mechanoreceptor dysfunction and aberrant processing of afferent input in the
spinal cord or brain may play a role in the pathophysiology of visceral hypersensitivity [16,17].
In one study, for example, the sensorial responses and the gastric tone responses to either gastric
accommodation or to cold stress were measured in 20 patients with functional dyspepsia and 20 healthy
controls [11]. Gastric compliance was similar in patients and controls; however, gastric distention elicited
more upper abdominal discomfort in the patients with dyspepsia. Similar findings were noted in another
observational study in which reduced perceptual thresholds or altered pain referral were found in 87
percent of patients with functional dyspepsia as compared with 20 percent of patients with organic causes
of dyspepsia [12].
Patients with dyspepsia may also have increased chemosensitivity. In one study, patients with functional
dyspepsia were significantly more likely to have nausea in response to acid infusion into the duodenal
bulb as compared with controls [13]. Patients with functional dyspepsia also had decreased duodenal
motor activity in the fasting state, resulting in decreased clearance of infused acid from the proximal
duodenum.
Helicobacter pylori infectionAlthough there are several hypotheses with regard to the role of
Helicobacter pylori (H. pylori) infection in the pathogenesis of functional dyspepsia, the mechanism
remains unclear.
H. pylori may cause altered smooth muscle dysfunction due to the induction of an inflammatory response
or by the initiation of an antibody response [18,19]. However, studies have not found an association
between H. pylori and abnormal gastric motor function in patients with functional dyspepsia [20]. (See
"Pathophysiology of and immune response to Helicobacter pylori infection".)
The inflammatory response induced by H. pylori may lower the discomfort threshold to gastric distension
by causing alterations in the enteric or central nervous system [18]. However, in at least one study, H.
pylori positive and negative patients with functional dyspepsia had no difference in the perception of
mechanically-induced gastric distension [21].
There is evidence from randomized controlled trials that eradication of H. pylori results in relief of
dyspepsia in a minority of patients. However, studies have failed to establish a temporal relationship
between H. pylori infection and functional dyspepsia, or the association of H. pylori with a specific
symptom complex [18]. Therefore, relief of dyspepsia may reflect other factors such as cure of
unrecognized peptic ulcer disease in patients misdiagnosed with functional (nonulcer) dyspepsia.
Altered gut microbiomeAlterations in the upper gastrointestinal tract microbiome may result in the
development of dyspepsia, although this has not been directly, formally evaluated.
This hypothesis is supported by the observation that dyspeptic symptoms are more likely to occur after an
episode of gastroenteritis [22-24]. In one study, patients were noted to have persistent symptoms eight
years after exposure to a waterborne outbreak of bacterial dysentery [24]. It has also been hypothesized
that the efficacy of H. pylori therapy in improving symptoms of functional dyspepsia is due to the impact
on the gut microbiome rather than the eradication of H. pylori alone [25].
An association between functional dyspepsia and increased duodenal eosinophilia has been reported,
with an increase in duodenal eosinophils in patients with early satiety [26-30]. However, increased
duodenal eosinophilia can occur in a healthy population [31,32]. It is also unclear if this upregulation in
mucosal immunity is due to changes in the upper gut microbiome or diet.
9/21/2013
Page 3 of 15
Psychosocial dysfunctionFunctional dyspepsia may result from a complex interaction of

psychosocial and physiological factors [33]. Dyspepsia has been associated with generalized anxiety
disorder, somatization, and major depression [7,34-36]. There is also a higher prevalence of functional
gastrointestinal disorders in patients with self-reported history of childhood abuse [37,38]. In a prospective
study, depression at baseline was predictive of the new onset of functional dyspepsia at 12-year follow-up
[39].
DIAGNOSISThe diagnosis of functional (idiopathic or nonulcer) dyspepsia is made from the
characteristic clinical history of postprandial fullness, early satiety, or epigastric pain/ burning for the last
three months with symptom onset at least six months before diagnosis and the exclusion of other causes
of dyspepsia with upper endoscopy and additional testing, if indicated, based on the symptoms.
Gastroesophageal reflux disease can often be confused with functional dyspepsia, as dyspepsia
symptoms commonly coexist with heartburn, and some patients with functional dyspepsia respond to PPI
therapy. Gastroparesis is rare but can also be confused with functional dyspepsia, as gastric emptying
may be slow and symptoms of dyspepsia occur in both disorders [40]; vomiting or weight loss with very
slow gastric emptying suggest gastroparesis. The evaluation of a patient with dyspepsia to establish the
underlying cause is discussed in detail, separately. (See "Approach to the patient with dyspepsia".)
TREATMENTTreatment of patients with functional dyspepsia is controversial and alleviates symptoms
in only a small proportion of patients [41].
Initial approachPatients with functional dyspepsia should be tested and treated for H. pylori if the
local prevalence of H. pylori is >10 percent (table 2).
Proton pump inhibitors (PPIs) should be considered in patients with functional dyspepsia who test
negative for H. pylori, patients with persistent symptoms after eradication of H. pylori, or as empiric
therapy if the local prevalence of H. pylori is low (<5 percent) (table 3). (See 'Helicobacter pylori test and
treat' below and 'Antisecretory therapy' below.)
Either strategy, to test and treat for H. pylori or a trial of PPIs, may be considered in areas where the
prevalence of H. pylori is intermediate, 5 to 10 percent (table 3). The decision should include
consideration of the patient's age, past history, comorbidities, symptom duration, risk factors for H.
pyloriinfection,availabilityand cost of diagnostic testing, and patient preference.
If symptoms do not improve after eight weeks of PPI, a therapeutic trial with a tricyclic antidepressant
should be initiated. However, a large number of patients will continue to have symptoms despite this
approach and other therapies should be considered in these patients. (See 'Antidepressants' below and
'Subsequent approach' below.)
Helicobacter pylori test and treatHelicobacter pylori eradication is associated with significant
benefits in a subset of patients with functional dyspepsia [42,43]. We therefore recommend screening for
H. pylori, if the local prevalence of H. pylori is greater than 5 percent and if no biopsies for H. pylori were
performed on upper endoscopy as part of the evaluation of dyspepsia (table 2). Testing for H.
pylorishouldbeperformedwithaureabreathtestorstoolantigen assay. Serologic testing should not be
used due to their low positive predictive value. (See "Indications and diagnostic tests for Helicobacter
pylori infection".)
A systematic review of 17 randomized controlled trials included 3566 patients with functional dyspepsia.
Eradication of H. pylori was associated with a small but significant benefit, with treatment of 14 patients
needed to cure one case of functional dyspepsia (RRR 10 percent, 95% CI 6-14) [43,44]. In a subsequent
randomized controlled trial, 404 patients with functional dyspepsia and H. pylori were randomized to
9/21/2013
Page 4 of 15
treatment of H. pylori or placebo [43]. At 12-month follow-up, patients treated with H. pylori eradication
therapy were significantly more likely to have symptomatic improvement as compared with controls (49
versus 36 percent). (See "Treatment regimens for Helicobacter pylori".)
Antisecretory therapyAntisecretory therapy with a once daily proton pump inhibitor should be
considered in patients with functional dyspepsia with no evidence of H. pylori, persistent symptoms after
eradication of H. pylori, or as empiric therapy if the prevalence of H. pylori is low (<5 percent).
Proton pump inhibitorsPPIs appear to be moderately effective in the treatment of some
patients with functional dyspepsia (table 3) [45-47].
A meta-analysis of seven studies that included 3725 patients found that PPIs were significantly more
effective than placebo for reducing symptoms (RRR 10 percent, 95% CI 2.7-17.3) [45]. In a stratified
analysis, efficacy was confined to patients with predominant epigastric pain or reflux symptoms, but not in
those with predominant postprandial fullness, early satiety, bloating or belching.
H2 receptor antagonistsPatients with functional dyspepsia are more likely to respond to H2
receptor antagonists (H2RA) than to placebo. However, the effect of H2RAs in relieving symptoms of
functional dyspepsia is likely to be small [48].
In a 2006 meta-analysis that included 12 trials with a total of 2183 patients, H2RAs were associated with
a 23 percent reduction in symptoms compared to placebo (RRR 23 percent, 95% CI 8-35 percent) [47].
The NNT with H2RAs to improve one case of dyspepsia was seven subjects (95% CI 5-21). However, the
quality of most trials included was poor and there was significant heterogeneity among studies. Another
limitation of these studies is that patients with gastroesophageal reflux disease may have been
misclassified as having functional dyspepsia.
AntidepressantsCentral mechanisms may contribute to functional dyspepsia either through
increased upper gastrointestinal sensitivity or through other mechanisms. Tricyclic antidepressants should
be considered in patients with functional dyspepsia and persistent symptoms despite PPI therapy for eight
weeks.
A therapeutic trial should begin with a low dose (eg, amitriptyline or desipramine 10 to 25 mg at night or
trazodone 25 to 50 mg at night in women only, due to the risk of priapism in men), adjusting the dose
upward while observing for daytime sedation or other side effects. We usually advise trying the drug for 8
to 12 weeks before stopping if it is ineffective. If the patient responds in a few weeks, we usually continue
the drug for about six months and then try stopping the drug. It can be resumed if dyspepsia recurs.
In a randomized controlled trial, 107 patients with functional dyspepsia refractory to PPI therapy and
prokinetics were assigned to low dose imipramine (50 mg daily) or placebo for 12 weeks [49]. Patients
treated with imipramine were significantly less likely to have had a treatment failure at 12 weeks as
compared with placebo (22 versus 46 percent). However, patients on imipramine were significantly more
likely to have withdrawn from the study due to side effects. Low dose tricyclic antidepressant drugs may
also improve associated symptoms including insomnia and fibromyalgia [50,51].
There is no current evidence to support the use of selective serotonin reuptake inhibitors in patients with
functional dyspepsia [50,52]. The results of a large randomized controlled trial evaluating amitriptyline and
escitalopram may clarify their role in the management of patients with functional dyspepsia [53].
Subsequent approachThere are few therapeutic options for patients with functional dyspepsia who
fail to respond to initial management with H. pylori eradication, empiric PPI, and tricyclic antidepressant
[41]. Prokinetics can be considered in short courses. Antinociceptive agents can be considered in patients
9/21/2013
Page 5 of 15
who fail a four-week trial of prokinetic agents or those who cannot tolerate prokinetics. Psychotherapy
should be considered for motivated patients who associate symptoms with stressors.
Prokinetic agentsThe possible relationship between nonulcer dyspepsia and abnormal gastric
emptying provided the rationale for treatment trials of prokinetic agents [47]. We limit a trial of prokinetics,
such as metoclopramide (5 to 10 mg three times daily one-half an hour before meals and at night for
about four weeks), to patients in whom other therapies have failed.
Although meta-analyses have demonstrated an improvement in functional dyspepsia in patients treated
with prokinetics, these results are driven by small positive studies as larger studies were negative. The
effect may also reflect publication bias. In addition, several prokinetics are also associated with serious
side effects with long-term use and have limited availability.
A systematic review focusing on cisapride and domperidone (neither of which is available by prescription
in the United States) identified 17 placebo-controlled trials [54]. Global improvement in symptoms was
observed significantly more often with cisapride (OR 2.9, 95% CI 1.5-5.8) and domperidone (OR 7.0, 95%
CI 3.6-16) as compared with placebo. In a meta-analysis that included 19 trials with a total of 3178
patients, prokinetics were associated with a 33 percent reduction in symptoms as compared with placebo
(RRR 33 percent, 95% CI 18-45 percent) [47]. Domperidone is associated with a risk of QT prolongation
and arrhythmias. Domperidone can be obtained from United States compounding pharmacies.
Tegaserod, a partial 5-HT4 receptor agonist, improves gastric emptying and was superior to placebo in
relieving symptoms of functional dyspepsia but has been withdrawn from the United States market due to
possible cardiovascular side effects [55]. (See "Treatment of gastroparesis".)
Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory activity that has prokinetic
effects and probably also modulates gastric accommodation and hypersensitivity [56,57]. However, in two
phase III multicenter trials, itopride was not significantly better than placebo in relieving symptoms of
functional dyspepsia [58].
Acotiamide is an anticholinesterase drug that may improve gastric motility and gastric accommodation
[59]. While not commercially available, limited data suggest that acotiamide may improve symptoms in
patients with functional dyspepsia. In a phase III randomized controlled trial, 892 patients with functional
dyspepsia were randomly assigned to acotiamide or placebo for four weeks. Patients who received
acotiamide were more likely to have significant improvement in all three meal-related symptoms
(postprandial fullness, upper abdominal bloating, and early satiation; 15 versus 9 percent) and a higher
overall treatment response as compared with placebo (52 versus 35 percent) [60]. During the four-week
post-treatment follow-up period, improvement in meal related symptoms was sustained in patients treated
with acotiamide as compared with placebo. However, additional long-term trials are needed to confirm
these findings [61].
Fundic relaxant drugsThere is limited evidence that relaxing the gastric fundus may improve early
satiation and postprandial fullness. In a small randomized trial, as compared with placebo, buspirone (10
mg, three times daily for four weeks) increased gastric accommodation and reduced the overall severity of
symptoms of dyspepsia, despite slowing gastric emptying of liquids [62].
Antinociceptive agentsIt is hypothesized that antinociceptive agents may impact the central
processing of pain, thereby decreasing visceral hypersensitivity that has been associated with functional
dyspepsia. Carbamazepine, tramadol, or pregabalin can be considered in patients who fail a four-week
trial of prokinetic agents and in patients who cannot tolerate prokinetics.
However, it is important to recognize there are no successful trials of antinociceptives in patients with
functional dyspepsia and evidence to support their use in patients with functional dyspepsia is indirect. As
9/21/2013
Page 6 of 15
an example, a post hoc analysis of data obtained from six randomized controlled trials in patients with
generalized anxiety disorder and prominent gastrointestinal symptoms showed that pregabalin was
significantly more effective than placebo in treating both anxiety and gastrointestinal symptoms [63].
Psychological therapyPsychological therapy (cognitive behavioral therapy, hypnotherapy, or
psychotherapy) has benefited selected patients and should be considered for motivated patients who
associate symptoms with stressors [64-67]. (See "Overview of psychotherapies", section on 'Cognitive
and behavioral therapies'.)
Complementary and alternative medicineSeveral complementary and alternative medicine
approaches to functional dyspepsia have been described. However, further studies are needed before
they can be recommended [68].
A systematic review of several low quality studies involving herbal and natural products, acupuncture, and
homeopathy suggested a benefit from peppermint oil and STW5, a European multiherbal preparation that
includes peppermint and caraway [69]. STW5 may improve symptoms of functional dyspepsia by
stimulating gastric fundic relaxation and antral motility [5]. A subsequent eight-week placebo-controlled
trial also found symptomatic improvement in patients treated with STW5 [70].
Dietary modificationAlthough lipid and possibly other food substances instilled into the duodenum
can induce dyspepsia due to changes in gastric motility, there are limited data to support dietary
modification in patients with functional dyspepsia [71,72].
A population casecontrol study failed to find an association between various culprit foods and functional
gastrointestinal disorders [73].
INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at
the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient information: Stomach ache and stomach upset (The Basics)")
Beyond the Basics topics (see "Patient information: Upset stomach (functional dyspepsia) in adults
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Functional dyspepsia is defined as the presence of one or more of the following: postprandial
fullness, early satiation, epigastric pain or burning, and no evidence of structural disease (including
at upper endoscopy) to explain the symptoms. While patients with these symptoms and a negative
diagnostic evaluation likely have functional dyspepsia, according to the Rome III guidelines, the
criteria should be fulfilled for the last three months with symptom onset at least six months before
diagnosis. (See 'Definition' above.)
9/21/2013
Page 7 of 15
The diagnosis of functional dyspepsia is made by the exclusion of other causes of dyspepsia with
an upper endoscopy and additional testing, as indicated, based on the symptoms. The evaluation
of a patient with dyspepsia to establish the underlying cause is discussed in detail, separately. (See
"Approach to the patient with dyspepsia".)
Treatment of patients with functional dyspepsia is controversial and alleviates symptoms in only a
small proportion of patients. (See 'Treatment' above.)
An assessment of Helicobacter pylori should be performed if the local prevalence of H. pylori is >5
percent and if gastric biopsies were not obtained for H. pylori on upper endoscopy for evaluation for
dyspepsia (table 2). We suggest treatment for H. pylori in patients with functional dyspepsia who
test positive for an infection (Grade 2A). (See "Treatment regimens for Helicobacter pylori".)
We suggest a four- to eight-week trial of a once daily proton pump inhibitor in patients with
functional dyspepsia and no evidence of H. pylori, patients with persistent symptoms after
eradication of H. pylori, or as empiric therapy if the prevalence of H. pylori is low (<5 percent) (table
2 and table 3) (Grade 2A).
We suggest a tricyclic antidepressant drug for patients with persistent symptoms after an eightweek trial of a proton pump inhibitor, especially in patients with insomnia (Grade 2C). We start with
a low dose (eg, amitriptyline 10 mg at bedtime, desipramine 25 mg at bedtime, or trazodone 25 mg
at bedtime) and increase after a few days, usually to only two or three times these doses. (See
'Antidepressants' above.)
We suggest the use of prokinetics in patients in whom eradication of H. pylori and a trial of proton
pump inhibitor and tricyclic antidepressant has failed (Grade 2C). In such patients, we generally
limit a trial of metoclopramide to 5 to 10 mg three times daily one-half an hour before meals and at
night for about four weeks. The risk of side effects, including tardive dyskinesia, increase with the
cumulative dose and duration of treatment. (See 'Prokinetic agents' above.)
In patients who fail a four-week trial of prokinetic agents or in patients who cannot tolerate
prokinetics, treatment options include antinociceptive agents and psychological therapy. (See
'Psychological therapy' above.)
Several dietary, complementary, and alternative medicine approaches to functional dyspepsia have
been described. However, further studies are needed before these approaches can be routinely
recommended. (See 'Complementary and alternative medicine' above and 'Dietary modification'
above.)
Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Talley NJ, American Gastroenterological Association. American Gastroenterological Association
medical position statement: evaluation of dyspepsia. Gastroenterology 2005; 129:1753.
2. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology 2006;
130:1466.
3. Thumshirn M. Pathophysiology of functional dyspepsia. Gut 2002; 51 Suppl 1:i63.
4. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in
functional dyspepsia. Gastroenterology 1998; 115:1346.
9/21/2013
Page 8 of 15
5. Pilichiewicz AN, Horowitz M, Russo A, et al. Effects of Iberogast on proximal gastric volume,
antropyloroduodenal motility and gastric emptying in healthy men. Am J Gastroenterol 2007;
102:1276.
6. Karamanolis G, Caenepeel P, Arts J, Tack J. Association of the predominant symptom with clinical
characteristics and pathophysiological mechanisms in functional dyspepsia. Gastroenterology 2006;
130:296.
7. Scolapio JS, Camilleri M. Nonulcer dyspepsia. Gastroenterologist 1996; 4:13.
8. Koch KL, Stern RM. Functional disorders of the stomach. Semin Gastrointest Dis 1996; 7:185.
9. Quartero AO, de Wit NJ, Lodder AC, et al. Disturbed solid-phase gastric emptying in functional
dyspepsia: a meta-analysis. Dig Dis Sci 1998; 43:2028.
10. Delgado-Aros S, Camilleri M, Cremonini F, et al. Contributions of gastric volumes and gastric
emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology 2004;
127:1685.
11. Mearin F, Cucala M, Azpiroz F, Malagelada JR. The origin of symptoms on the brain-gut axis in
12. Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms and visceral perception in severe functional
and organic dyspepsia. Gut 1998; 42:814.
13. Samsom M, Verhagen MA, vanBerge Henegouwen GP, Smout AJ. Abnormal clearance of
exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients.
Gastroenterology 1999; 116:515.
14. Camilleri M, Malagelada JR, Kao PC, Zinsmeister AR. Gastric and autonomic responses to stress in
functional dyspepsia. Dig Dis Sci 1986; 31:1169.
15. Farr R, Vanheel H, Vanuytsel T, et al. In functional dyspepsia, hypersensitivity to postprandial
distention correlates with meal-related symptom severity. Gastroenterology 2013; 145:566.
16. Iovino P, Azpiroz F, Domingo E, Malagelada JR. The sympathetic nervous system modulates
perception and reflex responses to gut distention in humans. Gastroenterology 1995; 108:680.
17. Van Oudenhove L, Vandenberghe J, Dupont P, et al. Abnormal regional brain activity during rest
and (anticipated) gastric distension in functional dyspepsia and the role of anxiety: a H(2)(15)O-PET
study. Am J Gastroenterol 2010; 105:913.
18. Talley NJ, Hunt RH. What role does Helicobacter pylori play in dyspepsia and nonulcer dyspepsia?
Arguments for and against H. pylori being associated with dyspeptic symptoms. Gastroenterology
1997; 113:S67.
19. Berck P, De Giorgio R, Blennerhassett P, et al. Immune-mediated neural dysfunction in a murine
model of chronic Helicobacter pylori infection. Gastroenterology 2002; 123:1205.
20. Minocha A, Mokshagundam S, Gallo SH, Rahal PS. Alterations in upper gastrointestinal motility in
Helicobacter pylori-positive nonulcer dyspepsia. Am J Gastroenterol 1994; 89:1797.
21. Mearin F, de Ribot X, Balboa A, et al. Does Helicobacter pylori infection increase gastric sensitivity
in functional dyspepsia? Gut 1995; 37:47.
22. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset
23. Mearin F, Prez-Oliveras M, Perell A, et al. Dyspepsia and irritable bowel syndrome after a
Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology 2005;
129:98.
24. Ford AC, Thabane M, Collins SM, et al. Prevalence of uninvestigated dyspepsia 8 years after a
large waterborne outbreak of bacterial dysentery: a cohort study. Gastroenterology 2010; 138:1727.
25. Moayyedi P. Helicobacter pylori eradication for functional dyspepsia: what are we treating?:
comment on "Helicobacter pylori eradication in functional dyspepsia". Arch Intern Med 2011;
171:1936.
26. Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult
endoscopic population-based case-control study. Clin Gastroenterol Hepatol 2007; 5:1175.
9/21/2013
Page 9 of 15
27. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial
lymphocytosis as possible disease markers in the irritable bowel syndrome and functional
dyspepsia. Aliment Pharmacol Ther 2009; 29:765.
28. Moayyedi P. Dyspepsia. Curr Opin Gastroenterol 2012; 28:602.
29. Futagami S, Shindo T, Kawagoe T, et al. Migration of eosinophils and CCR2-/CD68-double positive
cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J
Gastroenterol 2010; 105:1835.
30. Walker MM, Talley NJ. Clinical value of duodenal biopsies--beyond the diagnosis of coeliac disease.
Pathol Res Pract 2011; 207:538.
31. Kato M, Kephart GM, Talley NJ, et al. Eosinophil infiltration and degranulation in normal human
tissue. Anat Rec 1998; 252:418.
32. DeBrosse CW, Case JW, Putnam PE, et al. Quantity and distribution of eosinophils in the
gastrointestinal tract of children. Pediatr Dev Pathol 2006; 9:210.
33. Drossman DA, Creed FH, Olden KW, et al. Psychosocial aspects of the functional gastrointestinal
disorders. Gut 1999; 45 Suppl 2:II25.
34. Castillo EJ, Camilleri M, Locke GR, et al. A community-based, controlled study of the epidemiology
and pathophysiology of dyspepsia. Clin Gastroenterol Hepatol 2004; 2:985.
35. Goodwin RD, Cowles RA, Galea S, Jacobi F. Gastritis and mental disorders. J Psychiatr Res 2013;
47:128.
36. Mak AD, Wu JC, Chan Y, et al. Dyspepsia is strongly associated with major depression and
generalised anxiety disorder - a community study. Aliment Pharmacol Ther 2012; 36:800.
37. Drossman DA, Talley NJ, Leserman J, et al. Sexual and physical abuse and gastrointestinal illness.
Review and recommendations. Ann Intern Med 1995; 123:782.
38. Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Gastrointestinal tract symptoms and selfreported abuse: a population-based study. Gastroenterology 1994; 107:1040.
39. Koloski NA, Jones M, Kalantar J, et al. The brain--gut pathway in functional gastrointestinal
disorders is bidirectional: a 12-year prospective population-based study. Gut 2012; 61:1284.
40. Lacy BE. Functional dyspepsia and gastroparesis: one disease or two? Am J Gastroenterol 2012;
107:1615.
41. Lacy BE, Talley NJ, Locke GR 3rd, et al. Review article: current treatment options and management
of functional dyspepsia. Aliment Pharmacol Ther 2012; 36:3.
42. Moayyedi P, Deeks J, Talley NJ, et al. An update of the Cochrane systematic review of Helicobacter
pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic
reviews. Am J Gastroenterol 2003; 98:2621.
43. Mazzoleni LE, Sander GB, Francesconi CF, et al. Helicobacter pylori eradication in functional
dyspepsia: HEROES trial. Arch Intern Med 2011; 171:1929.
44. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia.
Cochrane Database Syst Rev 2005; :CD002096.
45. Wang WH, Huang JQ, Zheng GF, et al. Effects of proton-pump inhibitors on functional dyspepsia: a
meta-analysis of randomized placebo-controlled trials. Clin Gastroenterol Hepatol 2007; 5:178.
46. Moayyedi P, Delaney BC, Vakil N, et al. The efficacy of proton pump inhibitors in nonulcer
dyspepsia: a systematic review and economic analysis. Gastroenterology 2004; 127:1329.
47. Moayyedi P, Soo S, Deeks J, et al. Pharmacological interventions for non-ulcer dyspepsia.
Cochrane Database Syst Rev 2006; :CD001960.
48. Abraham NS, Moayyedi P, Daniels B, Veldhuyzen Van Zanten SJ. Systematic review: the
methodological quality of trials affects estimates of treatment efficacy in functional (non-ulcer)
dyspepsia. Aliment Pharmacol Ther 2004; 19:631.
49. Wu JC, Cheong PK, Chan YC, et al. A randomized, double-blind, placebo-controlled trial of low
dose imipramine for treatment of refractory functional dyspepsia (FD) (abstract #216).
Gastroenterology 2011; 140:S50.
9/21/2013
Page 10 of 15
50. Jackson JL, O'Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with
antidepressant medications: a meta-analysis. Am J Med 2000; 108:65.
51. Mertz H, Fass R, Kodner A, et al. Effect of amitriptyline on symptoms, sleep, and visceral perception
in patients with functional dyspepsia. Am J Gastroenterol 1998; 93:160.
52. van Kerkhoven LA, Laheij RJ, Aparicio N, et al. Effect of the antidepressant venlafaxine in functional
dyspepsia: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2008;
6:746.
53. Talley NJ, Locke GR 3rd, Herrick LM, et al. Functional Dyspepsia Treatment Trial (FDTT): a doubleblind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating
symptoms, psychopathology, pathophysiology and pharmacogenetics. Contemp Clin Trials 2012;
33:523.
54. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, Talley NJ. Efficacy of cisapride and
domperidone in functional (nonulcer) dyspepsia: a meta-analysis. Am J Gastroenterol 2001; 96:689.
55. Vakil N, Laine L, Talley NJ, et al. Tegaserod treatment for dysmotility-like functional dyspepsia:
results of two randomized, controlled trials. Am J Gastroenterol 2008; 103:1906.
56. Iwanaga Y, Miyashita N, Saito T, et al. Gastroprokinetic effect of a new benzamide derivative
itopride and its action mechanisms in conscious dogs. Jpn J Pharmacol 1996; 71:129.
57. Holtmann G, Talley NJ, Liebregts T, et al. A placebo-controlled trial of itopride in functional
dyspepsia. N Engl J Med 2006; 354:832.
58. Talley NJ, Tack J, Ptak T, et al. Itopride in functional dyspepsia: results of two phase III multicentre,
randomised, double-blind, placebo-controlled trials. Gut 2008; 57:740.
59. Seto K, Sasaki T, Katsunuma K, et al. Acotiamide hydrochloride (Z-338), a novel prokinetic agent,
restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.
Neurogastroenterol Motil 2008; 20:1051.
60. Matsueda K, Hongo M, Tack J, et al. A placebo-controlled trial of acotiamide for meal-related
symptoms of functional dyspepsia. Gut 2012; 61:821.
61. Bytzer P. New hope for functional dyspepsia? Gut 2012; 61:789.
62. Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with
functional dyspepsia. Clin Gastroenterol Hepatol 2012; 10:1239.
63. Stein DJ, Bruce Lydiard R, Herman BK, Mandel FS. Impact of gastrointestinal symptoms on
response to pregabalin in generalized anxiety disorder: results of a six-study combined analysis. Int
Clin Psychopharmacol 2009; 24:126.
64. Hamilton J, Guthrie E, Creed F, et al. A randomized controlled trial of psychotherapy in patients with
chronic functional dyspepsia. Gastroenterology 2000; 119:661.
65. Mine K, Kanazawa F, Hosoi M, et al. Treating nonulcer dyspepsia considering both functional
disorders of the digestive system and psychiatric conditions. Dig Dis Sci 1998; 43:1241.
66. Jones MP, Maganti K. Symptoms, gastric function, and psychosocial factors in functional dyspepsia.
J Clin Gastroenterol 2004; 38:866.
67. Calvert EL, Houghton LA, Cooper P, et al. Long-term improvement in functional dyspepsia using
hypnotherapy. Gastroenterology 2002; 123:1778.
68. Zeng F, Qin W, Ma T, et al. Influence of acupuncture treatment on cerebral activity in functional
dyspepsia patients and its relationship with efficacy. Am J Gastroenterol 2012; 107:1236.
69. Koretz RL, Rotblatt M. Complementary and alternative medicine in gastroenterology: the good, the
bad, and the ugly. Clin Gastroenterol Hepatol 2004; 2:957.
70. von Arnim U, Peitz U, Vinson B, et al. STW 5, a phytopharmacon for patients with functional
dyspepsia: results of a multicenter, placebo-controlled double-blind study. Am J Gastroenterol 2007;
102:1268.
71. Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in
patients with functional dyspepsia. Dig Dis Sci 1995; 40:1636.
72. Feinle C, Meier O, Otto B, et al. Role of duodenal lipid and cholecystokinin A receptors in the
pathophysiology of functional dyspepsia. Gut 2001; 48:347.
9/21/2013
Page 11 of 15
73. Saito YA, Locke GR 3rd, Weaver AL, et al. Diet and functional gastrointestinal disorders: a
population-based case-control study. Am J Gastroenterol 2005; 100:2743.
Topic 19 Version 14.0
9/21/2013
Page 12 of 15
GRAPHICS
Diagnostic criteria for functional dyspepsia
Diagnostic criteria for functional dyspepsia*
One or more of:
1. Bothersome postprandial fullness
2. Early satiation
3. Epigastric pain
4. Epigastric burning
AND
No evidence of structural disease (including at upper endoscopy) that is likely to explain the
symptoms
Diagnostic criteria for postprandial distress syndrome*

Must include one or both of the following:
1. Bothersome postprandial fullness, occurring after ordinary sized meals, at least several times
per week
2. Early satiation that prevents finishing a regular meal, at least several times a week
Supportive criteria
1. Upper abdominal bloating or postprandial nausea or excessive belching can be present
2. Epigastric pain syndrome may coexist
Diagnostic criteria for epigastric pain syndrome*

Must include all of the following:
1. Pain or burning localized to other abdominal or chest regions
2. The pain is intermittent
3. Not generalized or localized to other abdominal or chest regions
4. Not relieved by defecation or passage of flatus
5. Not fulfilling criteria for gallbladder and sphincter of Oddi disorders
Supportive criteria
1. The pain may be of a burning quality but without a retrosternal component
2. The pain is commonly induced or relieved by ingestion of a meal but may occur while fasting
3. Postprandial distress syndrome may coexist
* Criteria must be fulfilled for the last three months with symptom onset at least six months before
diagnosis.
Reproduced from: Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders.
Gastroenterology 2006; 130:1466. Table used with the permission of Elsevier Inc. All rights
reserved.
9/21/2013
Page 13 of 15
Helicobacter pylori infection globally*

Country
Prevalence (percent)
Africa
Ethiopia
>95
Nigeria
70 to 91
Central America
Guatemala
Mexico
65
70 to 90
North America
Canada
23
United States and Canada
30
South America
Brazil
82
Chile
70 to 90
Asia
Bangladesh
>90
India
80 to 88
Japan
55 to 70
Siberia
85
Sri Lanka
72
Taiwan
45 to 80
Australasia
Australia
20
Europe
(Eastern)
70
(Western)
30 to 50
Estonia
69
Germany
49
Iceland
36
Sweden
11
Switzerland
12 to 27
Middle East
Egypt
90
9/21/2013
Page 14 of 15
Libya
94
Saudi Arabia
80
Turkey
80
* This table gives prevalence rates of H pylori internationally, but rates can vary within countries by
region or practice setting.
Reproduced with permission from: Hunt RH, Xiao SD, Megraud F, et al. World Gastroenterology
Organisation Global Guidelines: Helicobacter pylori in developing countries. World Gastroenterology
Organisation, August 2010. p.4. Copyright 2013 World Gastroenterology Organization.
9/21/2013
Page 15 of 15
Recommendations for PPI doses in the treatment of acid-related

disorders
Drug
Dose (adult) oral
Active and maintenance therapy of gastroduodenal ulcers*

Dexlansoprazole
30 to 60 mg
Esomeprazole
20 to 40 mg
Lansoprazole
15 to 30 mg
Omeprazole
20 to 40 mg
Pantoprazole
20 to 40 mg
Rabeprazole
20 mg
All administered daily before breakfast

Primary and secondary prevention of NSAID-induced ulcers
All PPIs as above
Treatment of erosive or nonerosive gastroesophageal reflux disease
Dexlansoprazole
30 mg daily or 30 mg twice daily
Esomeprazole
20 or 40 mg daily
Lansoprazole
Omeprazole
20 to 40 mg daily or 20 mg twice daily
Pantoprazole
Rabeprazole
All administered daily before breakfast, second dose if necessary should be given before
evening meal
PPI: proton pump inhibitor; NSAID: nonsteroidal antiinflammatory drug.
* As a general rule, active duodenal ulcers should be treated for four weeks and gastric ulcers for
eight weeks.
Meals should ideally contain protein to enhance parietal cell stimulation.
Adapted from: Wolfe MM, Sachs G. Acid suppression: Optimizing therapy for gastroduodenal ulcer
healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology
2000; 118:S9.
9/21/2013

Dispepsia Functionala Utd

Uploaded by

Copyright:

Available Formats

You might also like

Dispepsia Functionala Utd

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Dispepsia Functionala Utd

Uploaded by

Copyright:

Available Formats

Functional dyspepsia

Official reprint from UpToDate

www.uptodate.com 2013 UpToDate

Visceral hypersensitivityVisceral hypersensitivity is characterized by a lowered threshold for

Psychosocial dysfunctionFunctional dyspepsia may result from a complex interaction of

Use of UpToDate is subject to the Subscription and License Agreement.

Diagnostic criteria for postprandial distress syndrome*

Diagnostic criteria for epigastric pain syndrome*

Helicobacter pylori infection globally*

United States and Canada

Recommendations for PPI doses in the treatment of acid-related

Dose (adult) oral

Active and maintenance therapy of gastroduodenal ulcers*

All administered daily before breakfast

30 mg daily or 30 mg twice daily

30 mg daily or 30 mg twice daily

20 to 40 mg daily or 20 mg twice daily

40 mg daily or 40 mg twice daily

20 mg daily or 20 mg twice daily

You might also like