Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V.
Functional gastroduodenal disorders.
Gastroenterology. 2006 Apr;130(5):1466-79. doi: 10.1053/j.gastro.2005.11.059.
Abstract/Text
A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders is proposed. Four categories of functional gastroduodenal disorders are distinguished. The first category, functional dyspepsia, groups patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation. Based on recent evidence and clinical experience, a subgroup classification is proposed for postprandial distress syndrome (early satiation or postprandial fullness) and epigastric pain syndrome (pain or burning in the epigastrium). The second category, belching disorders, comprises aerophagia (troublesome repetitive belching with observed excessive air swallowing) and unspecified belching (no evidence of excessive air swallowing). The third category, nausea and vomiting disorders, comprises chronic idiopathic nausea (frequent bothersome nausea without vomiting), functional vomiting (recurrent vomiting in the absence of self-induced vomiting, or underlying eating disorders, metabolic disorders, drug intake, or psychiatric or central nervous system disorders), and cyclic vomiting syndrome (stereotypical episodes of vomiting with vomiting-free intervals). The rumination syndrome is a fourth category of functional gastroduodenal disorder characterized by effortless regurgitation of recently ingested food into the mouth followed by rechewing and reswallowing or expulsion. The proposed classification requires further research and careful validation but the criteria should be of value for clinical practice; for epidemiological, pathophysiological, and clinical management studies; and for drug development.
Functional Dyspepsia：Tominaga K. and Kusunoki H., editors, Springer, 2018.
Stanghellini V.
Three-month prevalence rates of gastrointestinal symptoms and the influence of demographic factors: results from the Domestic/International Gastroenterology Surveillance Study (DIGEST).
Scand J Gastroenterol Suppl. 1999;231:20-8. doi: 10.1080/003655299750025237.
Abstract/Text
BACKGROUND: This paper reports the 3-month prevalence rates of gastrointestinal (GI) symptoms from the Domestic/International Gastroenterology Surveillance Study (DIGEST), and their relationship with demographic factors; namely age, gender and body mass index (BMI).
METHODS: Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with randomly selected members of the general population aged 18 years and over (50.6% female; mean age 44 years). The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms, or no GI symptoms. Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom: gastro-oesophageal reflux (GORD)-like symptoms, ulcer-like symptoms or dysmotility-like symptoms. Symptoms were classified as relevant if they were of at least moderate severity and/or occurred at least once a week.
RESULTS: A mean of 46.4% of subjects reported experiencing one or more of the 14 GI symptoms, with 28.1% experiencing upper GI symptoms classified as relevant. Significant differences between the prevalences of relevant symptoms were evident between sampling sites. The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7%. For ulcer-like symptoms, prevalence was 4.1%, and for dysmotility-like symptoms 15.5%. Significant differences were observed in the prevalence rates of symptom groups between countries. Women were significantly more likely than men to experience relevant symptoms, with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms. The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age; ulcer-like symptoms showed no significant relationship with age; and dysmotility-like symptoms decreased significantly with age. The prevalence of relevant symptoms increased with increasing BMI.
CONCLUSIONS: In conclusion, the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms, and their association with biological factors.
Miwa H.
Life style in persons with functional gastrointestinal disorders--large-scale internet survey of lifestyle in Japan.
Neurogastroenterol Motil. 2012 May;24(5):464-71, e217. doi: 10.1111/j.1365-2982.2011.01872.x. Epub 2012 Jan 31.
Abstract/Text
BACKGROUND: Care of patients with functional gastrointestinal disorders (FGIDs) commonly includes offering guidance on diet, exercise, and other lifestyle factors, but there is little information available on the actual lifestyles of FGID sufferers.
METHODS: An internet questionnaire survey of 15,000 adult members of the general public in Japan who were screened for functional dyspepsia (FD) and irritable bowel syndrome (IBS) using the Rome III adult FGID questionnaire was conducted.
KEY RESULTS: The prevalence of FD and IBS was 6.5% and 14.0%, respectively, and 3.0% of the subjects met the criteria for both FD and IBS. The prevalence of both FD and IBS was higher in women than in men. The lifestyles of 2,547 subjects who met the Rome III criteria for FD, IBS, or both were compared with the lifestyles of 1,000 control subjects who did not meet the criteria for FD or the criteria for IBS. Compared to the control subjects, a significantly lower percentage of subjects with FD, IBS, or both exercised frequently, and a significantly higher percentage thought that their sleep was insufficient, ate meals irregularly, did not have an appetite, did not like meat, thought that their vegetable consumption was insufficient, felt stress in their daily lives, and regarded themselves as being highly susceptible to stress.
CONCLUSIONS & INFERENCES: Persons with FGIDs are affected by impairment of sleep, eating habits, diet, exercise and other lifestyle factors, and feel excessive stress. This suggests that offering lifestyle guidance to FGID patients may be useful.
© 2012 Blackwell Publishing Ltd.
Kinoshita Y, Chiba T; FUTURE Study Group.
Characteristics of Japanese patients with chronic gastritis and comparison with functional dyspepsia defined by ROME III criteria: based on the large-scale survey, FUTURE study.
Intern Med. 2011;50(20):2269-76. doi: 10.2169/internalmedicine.50.5678. Epub 2011 Oct 15.
Abstract/Text
OBJECTIVE: To clarify the clinical characteristics of patients diagnosed with chronic gastritis in Japan, a large scale clinical survey of patients with chronic upper gastrointestinal symptoms was conducted. Patients diagnosed with functional dyspepsia (FD) according to the ROME III criteria were selected from among patients with chronic gastritis and the clinical characteristics of patients with FD and those with chronic gastritis were compared.
PATIENTS AND METHODS: Patients with upper abdominal symptoms and diagnosed with chronic gastritis were enrolled in the study. Their main complaints, duration of symptoms, clinical characteristics, mental state, and results of endoscopic examinations, if available, were prospectively surveyed. Quality of life (QOL) impairment caused by abdominal symptoms was also surveyed using the Izumo QOL scale.
RESULTS: A total of 9,125 patients with a clinical diagnosis of chronic gastritis were enrolled in the survey. Of those, approximately 60% had more than 2 symptoms and QOL impairment was greater in cases with multiple symptoms. Endoscopic examinations were performed in 2,946 cases (32.3% of enrolled patients), during which gastric and/or esophageal carcinoma was found in only 0.2%, though organic diseases were found in 6.2%. Endoscopic examinations were not done for patients with high risks of organic diseases. Of patients with organic diseases excluded by an endoscopic examination, only 362 (12.3% of patients who underwent an endoscopy) were diagnosed with FD according to the ROME III criteria, mainly because of short symptom duration. There were no remarkable differences in regard to clinical characteristics, including symptoms and mental state, between patients with chronic gastritis and those with FD.
CONCLUSION: Clinical characteristics of patients with chronic gastritis were similar to those with FD, except for shorter symptom duration.
Miwa H, Ghoshal UC, Fock KM, Gonlachanvit S, Gwee KA, Ang TL, Chang FY, Hongo M, Hou X, Kachintorn U, Ke M, Lai KH, Lee KJ, Lu CL, Mahadeva S, Miura S, Park H, Rhee PL, Sugano K, Vilaichone RK, Wong BC, Bak YT.
Asian consensus report on functional dyspepsia.
J Gastroenterol Hepatol. 2012 Apr;27(4):626-41. doi: 10.1111/j.1440-1746.2011.07037.x.
Abstract/Text
BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia.
METHODS: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group.
RESULTS: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added.
CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, Talley NJ.
Gastroduodenal Disorders.
Gastroenterology. 2016 May;150(6):1380-92. doi: 10.1053/j.gastro.2016.02.011.
Abstract/Text
Symptoms that can be attributed to the gastroduodenal region represent one of the main subgroups among functional gastrointestinal disorders. A slightly modified classification into the following 4 categories is proposed: (1) functional dyspepsia, characterized by 1 or more of the following: postprandial fullness, early satiation, epigastric pain, and epigastric burning, which are unexplained after a routine clinical evaluation; and includes 2 subcategories: postprandial distress syndrome that is characterized by meal-induced dyspeptic symptoms and epigastric pain syndrome that does not occur exclusively postprandially; the 2 subgroups can overlap; (2) belching disorders, defined as audible escapes of air from the esophagus or the stomach, are classified into 2 subcategories, depending on the origin of the refluxed gas as detected by intraluminal impedance measurement belching: gastric and supragastric belch; (3) nausea and vomiting disorders, which include 3 subcategories: chronic nausea and vomiting syndrome; cyclic vomiting syndrome; and cannabinoid hyperemesis syndrome; and (4) rumination syndrome.
Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
Talley NJ, Weaver AL, Zinsmeister AR.
Impact of functional dyspepsia on quality of life.
Dig Dis Sci. 1995 Mar;40(3):584-9. doi: 10.1007/BF02064375.
Abstract/Text
Little information on functional status and well-being is available in patients with functional gastrointestinal disease. We aimed to evaluate whether quality of life is poorer in patients with functional dyspepsia. A consecutive sample of 73 patients with functional dyspepsia completed a validated questionnaire prior to endoscopy. Organic disease controls comprised 658 outpatients attending endoscopy. Quality of life was measured using the validated Medical Outcomes Survey (which assessed physical, role, and social functioning; mental health; health perception; and any bodily pain) and the Brief Symptom Inventory (for current anxiety and depression); additional specific gastrointestinal items were also included. A stepwise logistic regression analysis was used to assess the association between diagnostic group and the quality of life measures, adjusting for potential confounders. Patients who reported more interruptions in their daily activities due to abdominal pain and who had fewer limitations of physical functioning were more likely to have functional dyspepsia (vs other disease, P < 0.01). Mental health, social functioning, and health perception also tended to be poorer in functional dyspepsia. We conclude that quality of life may be more impaired in patients with functional dyspepsia than in patients with other conditions who present for upper endoscopy.
Kaji M, Fujiwara Y, Shiba M, Kohata Y, Yamagami H, Tanigawa T, Watanabe K, Watanabe T, Tominaga K, Arakawa T.
Prevalence of overlaps between GERD, FD and IBS and impact on health-related quality of life.
J Gastroenterol Hepatol. 2010 Jun;25(6):1151-6. doi: 10.1111/j.1440-1746.2010.06249.x.
Abstract/Text
OBJECTIVE: Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common, and have negative impacts on health-related quality of life (HR-QOL). Several studies demonstrated a significant overlap between two of these three diseases. The purpose of this study was to examine the prevalence of GERD, FD, and IBS, their overlap rates, and HR-QOL for each disease and each overlap compared with healthy controls in the Japanese general population.
METHODS: We performed a cross-sectional study of Japanese workers who visited a clinic for a routine health check-up, and asked them to fill out a self-report questionnaire. Prevalence and overlap rate of GERD defined as heartburn and/or acid regurgitation at least weekly, FD and IBS based on Rome III criteria, and HR-QOL by SF-8 were examined.
RESULTS: Of the 2680 eligible subjects, 207 (7.7%) were diagnosed as having GERD, 269 (10.0%) as FD, and 381 (14.2%) as IBS. Overlaps were found in 46.9% in GERD, 47.6% in FD, and 34.4% in IBS. Prevalence of overlaps in subjects with IBS was significantly lower compared with those among GERD or FD. Sufferers from GERD, FD, or IBS reported significantly poorer HR-QOL across all domains compared with controls. Overlaps significantly worsened HR-QOL in most domains except in the 'role emotional' domain. HR-QOL was particularly poor in the physical component summary for overlapping GERD and in the mental component summary for overlapping IBS.
CONCLUSION: Overlaps among GERD, FD and IBS were common and worsened HR-QOL in Japanese general population.
Jeong JJ, Choi MG, Cho YS, Lee SG, Oh JH, Park JM, Cho YK, Lee IS, Kim SW, Han SW, Choi KY, Chung IS.
Chronic gastrointestinal symptoms and quality of life in the Korean population.
World J Gastroenterol. 2008 Nov 7;14(41):6388-94. doi: 10.3748/wjg.14.6388.
Abstract/Text
AIM: To evaluate the prevalence of chronic gastrointestinal symptoms and their impact on health-related quality of life (HRQOL) in the Korean population.
METHODS: A cross-sectional survey, using a reliable and valid Rome II based questionnaire, was performed on randomly selected residents, between 18 and 69 years in age. All respondents were interviewed at their homes or offices by a team of interviewers. The impact of chronic gastrointestinal symptoms on HRQOL was assessed using the Korean version of the 36-item Short-Form general health survey (SF-36).
RESULTS: Of the 1807 eligible subjects, 1417 (78.4%: male 762; female 655) were surveyed. Out of the respondents, 18.6% exhibited at least one chronic gastrointestinal symptom. The prevalence of gastroesophageal reflux disease (GERD), defined as heartburn and/or acid regurgitation experienced at least weekly, was 3.5% (95% CI, 2.6-4.5). The prevalence of uninvestigated dyspepsia, irritable bowel syndrome (IBS) and chronic constipation based on Rome II criteria were 11.7% (95% CI, 10.1-13.5), 2.2% (95% CI, 1.5-3.1), and 2.6% (95% CI, 1.8-3.5) respectively. Compared with subjects without chronic gastrointestinal symptoms (n=1153), those with GERD (n=50), uninvestigated dyspepsia (n=166) and IBS (n=31) had significantly worse scores on most domains of the SF-36 scales.
CONCLUSION: The prevalence of GERD, uninvestigated dyspepsia and IBS were 3.5%, 11.7% and 2.2% respectively, in the Korean population. The health-related quality of life was significantly impaired in subjects with GERD, uninvestigated dyspepsia and IBS in this community.
Kindt S, Van Oudenhove L, Mispelon L, Caenepeel P, Arts J, Tack J.
Longitudinal and cross-sectional factors associated with long-term clinical course in functional dyspepsia: a 5-year follow-up study.
Am J Gastroenterol. 2011 Feb;106(2):340-8. doi: 10.1038/ajg.2010.406. Epub 2010 Oct 26.
Abstract/Text
OBJECTIVES: Functional dyspepsia (FD) is a heterogeneous disorder with different pathophysiological mechanisms underlying the symptom pattern, but little is known about its clinical course. The aims of this study were to study the long-term evolution of symptoms in a clinical FD population and to identify factors associated with outcome.
METHODS: FD patients who previously underwent gastric function testing and filled out a dyspepsia symptom score (DSS) were contacted. At follow-up, patients indicated whether symptoms had worsened, remained unchanged, improved, or disappeared. Anxiety and depression, DSS, chronic fatigue symptoms, irritable bowel syndrome (IBS) comorbidity, and FD-specific quality of life (QoL) were assessed using mailed questionnaires. Bivariate associations between different patient characteristics and DSS and QoL at follow-up were tested; multiple linear regression was used to identify factors associated with the outcomes, both longitudinally and cross-sectionally.
RESULTS: Data were obtained from 253 patients (84.9% of the eligible and consenting population (n=298) and 53.2% of the original population (n=476)). The mean duration of follow-up was 68±2 months. Disappeared, improved, unchanged, and worsened symptoms were reported by 17.4, 38.3, 30.8, and 13.4% of the patients, respectively. Correlations between dyspepsia symptoms at initial visit and follow-up were small to moderate in magnitude. DSS at initial visit and trait anxiety were longitudinally associated with DSS at follow-up, with a trend found for weight loss; depression, chronic fatigue, and IBS at follow-up were cross-sectionally associated with DSS. Trait anxiety, weight loss, and DSS at initial visit were independently associated with QoL at follow-up; depression as well as DSS and chronic fatigue at follow-up were cross-sectionally associated.
CONCLUSIONS: About half of FD patients reported disappeared or improved symptoms after a mean follow-up of 5 years. Although stability of symptom levels is low to moderate, DSS at initial visit, trait anxiety, and initial weight loss are more strongly associated with outcome than gastric sensorimotor function.
Pilichiewicz AN, Horowitz M, Holtmann GJ, Talley NJ, Feinle-Bisset C.
Relationship between symptoms and dietary patterns in patients with functional dyspepsia.
Clin Gastroenterol Hepatol. 2009 Mar;7(3):317-22. doi: 10.1016/j.cgh.2008.09.007. Epub 2008 Sep 20.
Abstract/Text
BACKGROUND & AIMS: Patients with functional dyspepsia (FD) often report that their symptoms are related to food ingestion. However, there is a lack of information about differences in eating patterns and nutrient intake between these patients and healthy individuals or the association with specific symptoms. We performed a prospective trial to evaluate the relationship between FD symptoms and dietary factors.
METHODS: Twenty patients with FD (17 women) and 21 healthy subjects (18 women) completed detailed diet diaries, recording all foods eaten, drinks consumed, and times of consumption, as well as the occurrence, timing, and severity of dyspeptic symptoms (ie, nausea, discomfort, fullness, bloating, upper-abdominal/epigastric pain) for 7 days. Data from the diet diaries were analyzed for the number of meals, light meals, snacks and drinks, energy intake, and macronutrient distribution.
RESULTS: Patients with FD ate fewer meals (P < .01) and consumed less total energy (P = .1) and fat (P = .1) than healthy subjects. Their symptoms were modest in severity (score out of 10; 5 [range, 3-8]) and occurred within 31 minutes (range, 8-64 min) of eating. Fullness was related directly to the amount of fat ingested (z, 1.91; P < .05) and overall energy intake (z, 2.12; P < .05) and related inversely to the amount of carbohydrate ingested (z, -1.9; P = .05). Similarly, bloating was related to the amount of fat ingested (z, 1.68; P = .09). There was no significant relationship between symptom severity and any of the dietary variables measured.
CONCLUSIONS: Management of patients with FD might be improved by instructing them to consume smaller meals with reduced fat content.
Aro P, Talley NJ, Ronkainen J, Storskrubb T, Vieth M, Johansson SE, Bolling-Sternevald E, Agréus L.
Anxiety is associated with uninvestigated and functional dyspepsia (Rome III criteria) in a Swedish population-based study.
Gastroenterology. 2009 Jul;137(1):94-100. doi: 10.1053/j.gastro.2009.03.039. Epub 2009 Mar 26.
Abstract/Text
BACKGROUND & AIMS: The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes: postprandial distress syndrome and epigastric pain syndrome. We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria.
METHODS: We performed a cross-sectional population-based study in a primary care setting (the Kalixanda study). A random sample (n = 2860) of the adult population from 2 northern Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire to assess gastrointestinal symptoms (response rate, 74.2%; n = 2122). A randomly selected subgroup (n = 1001) of responders was invited to undergo an esophagogastroduodenoscopy (participation rate, 73.3%) including biopsy specimen collection, Helicobacter pylori culture and serology, and symptom assessments.
RESULTS: Of the 1001 subjects examined by endoscopy, 202 (20.2%; 95% confidence interval [CI], 17.7-22.7) were classified as having uninvestigated dyspepsia and 157 (15.7%; 95% CI, 13.4-18.0) as having functional dyspepsia. Major anxiety (Hospital Anxiety and Depression Scale score > or = 11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39-6.54), as was obesity (body mass index > or = 30 kg/m(2)) (OR, 1.86; 95% CI, 1.15-3.01). Major anxiety was associated with functional dyspepsia and postprandial distress syndrome (OR of 2.56 [95% CI, 1.06-6.19] and 4.35 [95% CI, 1.81-10.46], respectively), as was use of nonsteroidal anti-inflammatory drugs (OR, 2.49 [95% CI, 1.29-4.78] and 2.75 [95% CI, 1.38-5.50], respectively). Depression was not associated with any dyspepsia group.
CONCLUSIONS: Anxiety but not depression is linked to uninvestigated dyspepsia, functional dyspepsia, and postprandial distress syndrome but not to epigastric pain syndrome.
Hongo M, Harasawa S, Mine T, Sasaki I, Matsueda K, Kusano M, Hanyu N, Nakada K, Shibata C.
Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study (JMMS).
J Gastroenterol Hepatol. 2012 Jan;27(1):62-8. doi: 10.1111/j.1440-1746.2011.06949.x.
Abstract/Text
BACKGROUND AND AIM: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD.
METHODS: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated.
RESULTS: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication.
CONCLUSIONS: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Miwa H, Nagahara A, Tominaga K, Yokoyama T, Sawada Y, Inoue K, Ashida K, Fukuchi T, Hojo M, Yamashita H, Tomita T, Hori K, Oshima T.
Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial.
Am J Gastroenterol. 2009 Nov;104(11):2779-87. doi: 10.1038/ajg.2009.427. Epub 2009 Jul 28.
Abstract/Text
OBJECTIVES: Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD.
METHODS: In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals.
RESULTS: Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms.
CONCLUSIONS: Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.
Hojo M, Miwa H, Yokoyama T, Ohkusa T, Nagahara A, Kawabe M, Asaoka D, Izumi Y, Sato N.
Treatment of functional dyspepsia with antianxiety or antidepressive agents: systematic review.
J Gastroenterol. 2005 Nov;40(11):1036-42. doi: 10.1007/s00535-005-1687-8.
Abstract/Text
BACKGROUND: The pathophysiology of functional dyspepsia (FD) has not been elucidated precisely; accordingly, effective management of FD has not yet been found. Until now, treatment with antianxiety or antidepressive agents has been empirically applied; however, the efficacy of these treatments has not been established. We carried out this study to estimate the efficacy of these treatment approaches by systematically reviewing the literature concerning trials with agents that are efficacious against anxiety, neurosis, or depression.
METHODS: Articles were searched from the MEDLINE database up to October 2003, using the terms, "antianxiety agents", "antidepressants", and "dyspepsia", and from reference lists of published articles. Finally, studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles.
RESULTS: Thirteen articles, on 1717 patients, were selected from among 90 articles retrieved through our literature search. In 11 of the 13 studies, dyspeptic symptoms were improved significantly by treatment. Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents (pooled relative risk, 0.55; 95% confidence interval [CI], 0.36-0.85), although funnel plots were asymmetric.
CONCLUSIONS: Antianxiety or antidepressive agents may be effective in the treatment of FD patients, though further clinical trials are necessary.
Moayyedi P, Soo S, Deeks J, Forman D, Mason J, Innes M, Delaney B.
Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia. Dyspepsia Review Group.
BMJ. 2000 Sep 16;321(7262):659-64. doi: 10.1136/bmj.321.7262.659.
Abstract/Text
OBJECTIVES: To evaluate efficacy and cost effectiveness of Helicobacter pylori eradication treatment in patients with non-ulcer dyspepsia infected with H pylori.
DESIGN: Systematic review of randomised controlled trials comparing H pylori eradication with placebo or another drug treatment. Results were incorporated into a Markov model comparing health service costs and benefits of H pylori eradication with antacid treatment over one year.
DATA SOURCES: Six electronic databases were searched for randomised controlled trials from January 1966 to May 2000. Experts in the field, pharmaceutical companies, and journals were contacted for information on any unpublished trials. Trial reports were reviewed according to predefined eligibility and quality criteria.
MAIN OUTCOME MEASURES: Relative risk reduction for remaining dyspeptic symptoms (the same or worse) at 3-12 months. Cost per dyspepsia-free month estimated from Markov model based on estimated relative risk reduction.
RESULTS: Twelve trials were included in the systematic review, nine of which evaluated dyspepsia at 3-12 months in 2541 patients. H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost pound56 per dyspepsia-free month during first year after treatment.
CONCLUSION: H pylori eradication may be cost effective treatment for non-ulcer dyspepsia in infected patients but further evidence is needed on decision makers' willingness to pay for relief of dyspepsia.
Jin X, Li YM.
Systematic review and meta-analysis from Chinese literature: the association between Helicobacter pylori eradication and improvement of functional dyspepsia.
Helicobacter. 2007 Oct;12(5):541-6. doi: 10.1111/j.1523-5378.2007.00520.x.
Abstract/Text
OBJECTIVES: To evaluate the effect of eradicating Helicobacter pylori on dyspeptic symptoms in patients with functional dyspepsia in China.
DATA SOURCES: Randomized controlled trials conducted in China and those published between 1989 and April 2007.
REVIEW METHODS: The articles were retrieved from Chinese biomedicine Web database and Chinese scientific Journals database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics of chosen articles were displayed for further analysis, and summary odds ratio were calculated to determine the overall effect of H. pylori eradication. All the data were entered and analyzed using REVIEW MANAGER 4.1, and p < .05 was defined as statistically significant in all analysis.
RESULTS: Seven qualified trials were enrolled, and the summary odds ratio for improvement in dyspeptic symptoms in patients with functional dyspepsia in whom H. pylori was eradicated was 3.61 (95%CI: 2.62, 4.98, p < .00001). The difference in the follow-up period did not influence the final outcomes.
CONCLUSIONS: An improvement in dyspeptic symptoms occurred among Chinese patients with functional dyspepsia in whom H. pylori was eradicated.
Tominaga K, Sakata Y, Kusunoki H, Odaka T, Sakurai K, Kawamura O, Nagahara A, Takeuchi T, Fujikawa Y, Oshima T, Kato M, Furuta T, Murakami K, Chiba T, Miwa H, Kinoshita Y, Higuchi K, Kusano M, Iwakiri R, Fujimoto K, Tack JF, Arakawa T.
Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).
Neurogastroenterol Motil. 2018 Jul;30(7):e13319. doi: 10.1111/nmo.13319. Epub 2018 Mar 2.
Abstract/Text
BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients.
METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS).
KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016).
CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.
© 2018 John Wiley & Sons Ltd.
Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D.
Pharmacological interventions for non-ulcer dyspepsia.
Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001960. doi: 10.1002/14651858.CD001960.pub2. Epub 2004 Oct 18.
Abstract/Text
BACKGROUND: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that 450 million pounds is spent on dyspepsia drugs in the UK each year.
OBJECTIVES: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia.
SEARCH STRATEGY: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies.
SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD).
DATA COLLECTION AND ANALYSIS: Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects.
MAIN RESULTS: A total of 11796 citations were obtained. 157 trials were retrieved and 98 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 31 trials. The final 67 trials were included in the meta-analysis. Prokinetics (14 trials with dichotomous outcomes generating 1053 patients; relative risk reduction [RRR] = 48%; 95% confidence intervals [CI] = 27% to 63%), H2RAs (11 trials generating 2,164 patients; RRR = 22%; 95% CI = 7% to 35%) and PPIs (8 trials generating 3,293 patients; RRR = 14%; 95% CI = 5% to 22%) were significantly more effective than placebo. Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and H2RA results could be due to publication bias.
REVIEWERS' CONCLUSIONS: There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.
Matsueda K, Hongo M, Tack J, Aoki H, Saito Y, Kato H.
Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage.
Neurogastroenterol Motil. 2010 Jun;22(6):618-e173. doi: 10.1111/j.1365-2982.2009.01449.x. Epub 2010 Jan 5.
Abstract/Text
BACKGROUND: Acotiamide is a selective acetylcholinesterase inhibitor and enhances the actions of cholinergic neurons localized in the stomach.
METHODS: The present two studies were conducted to examine the optimal dosage of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia (FD) in Japan.
KEY RESULTS: The improvement rate of 'subjects global assessment of overall treatment efficacy (OTE)' at the final evaluation was approximately 10% higher in the acotiamide 100 mg group than that in the placebo group with good reproducibility though there was no significant differences at primary endpoint. The elimination rate of postprandial fullness in the acotiamide 100 mg group was significantly higher compared to placebo group. In addition, the post hoc analysis showed that in patients whose main complaints are meal-related symptoms such as postprandial fullness, upper abdominal bloating and/or early satiety, the improvement rate of 'OTE' at final evaluation in acotiamide 100 mg group was significantly superior to that in the placebo group.
CONCLUSIONS & INFERENCES: These results suggest that acotiamide possesses efficacy on FD and more specifically its meal-related symptoms of FD.
Talley NJ, Vakil N; Practice Parameters Committee of the American College of Gastroenterology.
Guidelines for the management of dyspepsia.
Am J Gastroenterol. 2005 Oct;100(10):2324-37. doi: 10.1111/j.1572-0241.2005.00225.x.
Abstract/Text
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 (> or =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.
Wang WH, Huang JQ, Zheng GF, Xia HH, Wong WM, Liu XG, Karlberg J, Wong BC.
Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials.
Clin Gastroenterol Hepatol. 2007 Feb;5(2):178-85; quiz 140. doi: 10.1016/j.cgh.2006.09.012. Epub 2006 Dec 14.
Abstract/Text
BACKGROUND & AIMS: The aim of this study was to assess systematically the efficacy of proton pump inhibitors (PPIs) in the treatment of functional dyspepsia compared with placebo and to determine if any difference in the response exists between symptom subgroups of functional dyspepsia.
METHODS: A literature search was performed through September 2005 in PubMed, Medline, Embase, CINAHL, and Cochrane databases to include randomized, double-blind, placebo-controlled trials evaluating the efficacy of PPIs for the treatment of functional dyspepsia. Relative risk (RR) and relative risk reduction (RRR) and 95% confidence intervals (CI) were calculated under a random-effects model.
RESULTS: Seven studies with a total of 3725 patients were identified. PPIs were found to be more effective than placebo for reducing symptoms in patients with functional dyspepsia (RRR, 10.3%; 95% CI, 2.7%-17.3%). The estimated number needed to treat is 14.6 (95% CI, 8.7-57.1). When stratified analyses were performed, a significant difference in the efficacy was observed only in patients with ulcer-like (RRR, 12.8%; 95% CI, 7.2%-18.1%) and reflux-like dyspepsia (RRR, 19.7%; 95% CI, 1.8%-34.3%), but not in those with dysmotility-like (RRR, 5.1%; 95% CI, -10.9% to 18.7%) and unspecified dyspepsia (RRR, -8.0%; 95% CI, -23.7% to 5.6%). The effect of H pylori on the efficacy of PPIs remains unclear. Significant heterogeneity among studies was found for the overall analysis, dysmotility-like dyspepsia, H pylori-negative subgroup, and different dose subgroups.
CONCLUSIONS: PPIs are more effective than placebo for the management of patients with ulcer-like and reflux-like functional dyspepsia.
Miwa H, Kusano M, Arisawa T, Oshima T, Kato M, Joh T, Suzuki H, Tominaga K, Nakada K, Nagahara A, Futagami S, Manabe N, Inui A, Haruma K, Higuchi K, Yakabi K, Hongo M, Uemura N, Kinoshita Y, Sugano K, Shimosegawa T; Japanese Society of Gastroenterology.
Evidence-based clinical practice guidelines for functional dyspepsia.
J Gastroenterol. 2015 Feb;50(2):125-39. doi: 10.1007/s00535-014-1022-3. Epub 2015 Jan 14.
Abstract/Text
General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world's first country to list "functional dyspepsia" as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor-patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). H. pylori eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.
Kusunoki H, Haruma K, Hata J, Ishii M, Kamada T, Yamashita N, Honda K, Inoue K, Imamura H, Manabe N, Shiotani A, Tsunoda T.
Efficacy of Rikkunshito, a traditional Japanese medicine (Kampo), in treating functional dyspepsia.
Intern Med. 2010;49(20):2195-202. doi: 10.2169/internalmedicine.49.3803. Epub 2010 Oct 15.
Abstract/Text
BACKGROUND: Rikkunshito, a traditional Japanese (Kampo) medicine, is widely prescribed as an oral preparation for the treatment of functional dyspepsia (FD). In our previous study, we reported that extracorporeal ultrasonography (US) is a useful technique for the assessment of the gastric accommodation reflex (AR) and duodenogastric motility. In this study, we examined the effects of Rikkunshito on the gastroduodenal function in patients with FD.
METHODS: Sixteen FD patients (median age, 45 y) underwent US, before and after 14 days of treatment with Rikkunshito (7.5 g b.d.). For assessment of the AR, a cross-sectional area of the proximal stomach was measured after incremental ingestion of a liquid meal up to 400-mL. The expansion rate was used as the parameter to determine the AR. Then, the gastric emptying rate (GER), motility index (MI), and reflux index (RI) were evaluated using previously reported methods.
RESULTS: Although no significant changes were observed in the total score of the Gastrointestinal Symptom Rating Scale (GSRS), the scores of 3 of the 15 symptoms of GSRS decreased significantly after treatment with Rikkunshito. The expansion rate of the proximal stomach was significantly greater after treatment with Rikkunshito than before the treatment. Although the GER and MI increased significantly, no significant differences in the RI were observed after treatment with Rikkunshito.
CONCLUSION: These observations suggested that Rikkunshito may be beneficial for the treatment of FD patients with impaired AR and gastric motility. These results also suggested that Rikkunshito has a therapeutic potential for FD and GERD.
Tatsuta M, Iishi H.
Effect of treatment with liu-jun-zi-tang (TJ-43) on gastric emptying and gastrointestinal symptoms in dyspeptic patients.
Aliment Pharmacol Ther. 1993 Aug;7(4):459-62. doi: 10.1111/j.1365-2036.1993.tb00120.x.
Abstract/Text
The effects of treatment with the Chinese herbal medicine Liu-Jun-Zi-Tang (TJ-43) on gastric emptying and gastrointestinal symptoms were investigated in 42 patients with chronic idiopathic dyspepsia. By random allocation, 22 patients received oral treatment with 2.5 g TJ-43 three times daily, and 20 patients received placebo. Gastric emptying was measured by the acetaminophen absorption method. After 7 days of treatment, gastric emptying was significantly accelerated and gastrointestinal symptoms were significantly reduced in patients treated with TJ-43. Placebo treatment produced no significant effects. These findings indicate that TJ-43 had a prokinetic action on gastric emptying and that it was useful in treating chronic dyspepsia.
