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Functional Dyspepsia Under-Recognized in Practice, Often Mislabeled GERD
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Experts have authored a review article on functional dyspepsia, which highlights the importance of a physician’s ability to recognize the condition, selective use of diagnostic upper GI endoscopy, and emerging treatments and management strategies.
“The global prevalence of functional dyspepsia in the community according to [Rome III criteria] is between 5% and 11%,” Nicholas J. Talley, MD, from the faculty of health and medicine at University of Newcastle in Australia, and Alexander C. Ford, MD, from Leeds Gastroenterology Institute at St. James’s University Hospital, and Leeds Institute of Biomedical and Clinical Sciences, University of Leeds in the U.K., wrote in the review article. “Costs associated with the condition in the United States in 2009 were in excess of $18 billion. It is therefore important that physicians be able to recognize functional dyspepsia, use investigations and diagnostic tests judiciously, and recommend effective treatments, in order to minimize the potential adverse social and economic effects of the condition.”
Nicholas J. Talley
Alexander C. Ford
Differentiating functional, organic dyspepsia
Despite efforts to standardize criteria for functional dyspepsia (FD) to minimize overlap with other functional GI disorders, studies show it may still be confused with other conditions.
“FD is under-recognized in practice, yet proper diagnosis facilitates optimal management,” Talley told Healio Gastroenterology. “Many cases are mislabeled GERD,” he said, and also gastroparesis, according to the review.
The main challenge in diagnosis is therefore in differentiating functional and organic forms of the disease, they wrote.
“The commonest FD symptoms are fullness after eating and inability to finish a normal sized meal,” Talley said. “These symptoms are often not volunteered unless specific questions are asked. Pain is less common.”
Upper GI endoscopy can usually determine the cause, and generally shows more than 70% of dyspepsia patients have FD. However, according to the review, “it is neither desirable nor realistic to perform this test in all patients with dyspepsia,” as it is costly and limited in its ability to identify organic disease.
Guidelines recommend dyspepsia patients with alarm symptoms undergo upper GI endoscopy to screen for gastroesophageal cancer, and for patients with simple dyspepsia without alarm symptoms, “it is reasonable to use [a noninvasive test for Helicobacter pylori infection] as a first-line strategy.”
In recent years, clinicians have moved toward subgrouping FD patients as having epigastric pain syndrome or postprandial distress syndrome, which may help guide therapy. Community-based studies support the approach, but referral population studies have shown some overlap between these subgroups.
“A new disease model postulates inflammation in the duodenum (including duodenal eosinophilia) explains a substantial subset with FD,” Talley said. “These observations are likely to change management in the future.”
Studies have also implicated psychological distress, genetic factors, infections, food intolerance or allergy in FD, though further research is needed.
Effective treatments, management strategies
Regarding the management of patients with FD, all “should be offered a positive diagnosis after targeted investigation, reassurance that the disorder does not negatively affect survival, and an explanation of the probable origin of symptoms,” according to the review. “Attention to stress reduction and lowering of anxiety is important, and dietary advice should be provided.”
However, the majority of conventional medical therapies have “limited efficacy,” they wrote.
“Advances in our understanding of the pathophysiology is changing management options,” Talley said. “For example, successful treatment of H. Pylori relieves FD in a subset.”
While the cost-effectiveness of H. pylori eradication as a management strategy has been demonstrated, a meta-analysis showed a relative risk of 0.9 (95% CI, 0.86-0.94) for persistent symptoms after eradication therapy. Other data suggest eradication therapy may be more beneficial in epigastric pain syndrome.
Reassurance is a common treatment strategy, and although it has not been tested in randomized trials for FD, other studies have shown the placebo-response rate is 30% to 40%.
Although acid-suppressive drugs have modest efficacy, “a trial of acid suppression seems to be a worthwhile strategy in most patients with [FD], particularly in those who have negative results on H. pylori testing,” or in those for whom eradication therapy did not improve symptoms, they wrote. “Antacids, bismuth, and sucralfate are not efficacious in [FD],” as is noted in the review.
Several prokinetic agents have been shown to lack efficacy or have unfavorable safety profiles. New agents were developed more recently, such as acotiamide, which is now approved in Japan for postprandial distress syndrome and is being tested in ongoing phase 3 trials in Western populations. Studies have also demonstrated efficacy for buspirone and tandospirone.
Antidepressants have long been suggested as second- or third-line therapies, but data from recent clinical trials “taken together … suggest that tricyclic antidepressants … should be preferred over selective serotonin-reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors,” they wrote. Preliminary data on psychological therapy is promising, and although further research is required, “such treatment should probably be considered for patients who have not had any improvement in their symptoms with conventional medical therapies, particularly in those with co-existing impairment of mood.”
While up to half of patients seek out alternatives to conventional medical therapies, “consistent evidence of the efficacy of acupuncture, homeopathy, or probiotics in [FD] is lacking,” though some herbal supplements may be beneficial.
Prognosis
Regarding the natural history of FD, Talley and Ford emphasized that for most patients it is “chronic and fluctuating, with periods of time when a patient is asymptomatic followed by episodes of symptom relapse.” This is true for 30% to 35% of patients with FD symptoms, whereas 15% to 20% will have persistent symptoms, and half will have symptom resolution. “Despite the chronic nature of [FD], there is no evidence to suggest that it is associated with decreased survival,” they concluded. – by Adam Leitenberger
Disclosures: Ford reports no relevant financial disclosures. Talley reports he has received lecture fees from the Rome Foundation and Takeda Pharmaceuticals; consulting fees from Yuhan, Adelphi Values, Prometheus Medical, Abbott Laboratories, Forest Laboratories (now Actavis), Furiex, Synergy Pharmaceuticals, Focus Communications and Zeria Pharmaceuticals; served as an unpaid consultant to GI Therapies; received honoraria from Janssen, Danone and GI Care; received study medication from Forest Laboratories; received grant support from the Rome Foundation, Ironwood Pharmaceuticals, Prometheus Medical, Janssen-Cilag, Takeda Pharmaceutical, Abbott Laboratories, Datapharm, Pfizer and Salix Pharmaceuticals; licensed the Bowel Disease Questionnaire and Mayo Dysphagia Questionnaire to the Mayo Clinic; and holds a patent related to the performance of a biomarker panel for IBS. Ford reports no relevant financial disclosures.
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