Evidence-based clinical practice guidelines for functional dyspepsia 2021

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan

Akihito Nagahara

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Akihiro Asakawa

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Makoto Arai

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Tadayuki Oshima

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Kunio Kasugai

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Kazuhiro Kamada

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Hidekazu Suzuki

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Fumio Tanaka

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Kazunari Tominaga

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Seiji Futagami

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Mariko Hojo

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Hiroshi Mihara

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Kazuhide Higuchi

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Motoyasu Kusano

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Tomiyasu Arisawa

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Mototsugu Kato

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Takashi Joh

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Satoshi Mochida

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Nobuyuki Enomoto

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Tooru Shimosegawa

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

Kazuhiko Koike

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

1 Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Functional Dyspepsia”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan

2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

Background

Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time.

Method

Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment.

Results and Conclusion

These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

Keywords: Dyspepsia, Guideline, Proton pump inhibitor, Prokinetics, Antianxiety drug, Antidepressant, Japanese traditional medicine, H. pylori eradication treatment, H. pylori-associated dyspepsia, Algorithm, Chronic gastritis

Introduction

Many people suffer from dyspeptic symptoms, but the cause is often unclear. Functional dyspepsia (FD) is a disorder that presents with chronic manifestation of such symptoms. Although FD is common, the disease name “functional dyspepsia” had not been widely used in routine medical practice because the concept of FD is relatively new and the name is difficult to understand. However, awareness of FD has been increasing gradually. Factors contributing to the increasing awareness include heightened concerns about quality of life (QOL) that have accompanied improved standards of living in Japan, concern that the stress associated with the growing complexity of modern life is contributing to the occurrence of dyspepsia, and the recognition of “functional dyspepsia” as a disease name for national insurance billing purposes in May 2013. In this context, clinical practice guidelines for FD were published by the Japanese Society of Gastroenterology (JSGE) in 2014, and the number of copies of those guidelines sold far exceeded that of any other guidelines published by the JSGE, indicating a high level of interest in FD.

In view of the rapid progress in medical research and clinical practice, JSGE has adopted a so-called sunset rule, which is a rule that clinical practice guidelines be revised every 5 years. In April 2017, on the basis of that rule, the Board of Directors of JSGE made the decision to revise the clinical practice guidelines for FD, and work on the revised guidelines was begun by the Guidelines Creation Committee. Like the previous version of the guidelines, the revised guidelines were also created using the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, it was decided to make the guidelines easier to understand by limiting the number of clinical questions (CQs). Therefore, issues that had already been clarified were handled as background questions (BQs) and questions for which a clear answer was not possible because of insufficient evidence were treated as future research questions (FRQs). The resulting guidelines were created from 24 BQs, 9 FRQs, and 7 CQs. The literature was searched systematically by the Japan Medical Library Association, with the search period being from 1983 to July 2020. The committee members discussed and finalized the proposed BQs, CQs, and FRQs and then voted to determine the recommendation grades. Next, the manuscript was checked and revised by the Evaluation Committee, and the revised manuscript was subjected to public comment by the members of JSGE. After final revision on the basis of the members’ comments, the Japanese manuscript was completed in January 2021 and published in April 2021.

The revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. Whereas previously organic disease had to be excluded by endoscopy to diagnose FD (the disease name “functional dyspepsia” could not be used for national insurance billing unless endoscopy had been performed), the revised guidelines specify that endoscopy should be performed in all cases where organic disease is suspected. Clinical determination of whether organic disease is suspected and endoscopy is necessary has been left to the judgment and discretion of the physician. Formerly, endoscopy had been required for a diagnosis of FD even in patients who were negative for Helicobacter pylori, patients as young as 20 years of age, and patients who had been screened for stomach cancer in the previous 6 months. The revised guidelines, however, have been changed to specify that rather than endoscopy being performed indiscriminately, the need for it should be determined for each patient depending on the patient’s physical findings, history (family, disease, tests), and other relevant factors. By eliminating unnecessary tests, this change is expected to bring many benefits, including reducing the physical and financial burden on patients, allowing their treatment to begin sooner, and helping control the cost of medical care to society.

The second major feature of the revised guidelines is the drug treatment options have been changed to reflect the latest evidence. Gastric acid-secretion inhibitors and prokinetic agents have been divided into different classes and a recommendation grade has been assigned to each class. The classes of gastric acid-secretion inhibitors are proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and potassium-competitive acid blockers (P-CABs), and the classes of prokinetic agents are acetylcholinesterase (AChE) inhibitors, dopamine receptor antagonists, and serotonin-4 (5-HT4) receptor agonists. Another important difference from the previous version of the guidelines is that the Japanese herbal medicine rikkunshito, for which there is abundant evidence, has been assigned a recommendation grade higher than that of other herbal medicines. These changes are in line with the spirit of JSGE guidelines, which is to build treatment systems based on evidence. As an aide for implementing the revised guidelines, an algorithm for the diagnosis and treatment of FD that reflects the new position of endoscopy and the recommendation grades of the available treatments has been prepared.

This article summarizes the Japanese guidelines, with particular focus on the treatment section. To prepare the guidelines, specialists in relevant fields in Japan collected evidence, discussed it, and then voted on it, so the guidelines are based on the current situation in Japan. Among the diverse countries and regions of the world, there are great differences in disease occurrence, the medical resources available, and the medical environments, as well as in lifestyles and cultures. Therefore, the authors think that standardization of medical care for dyspepsia in each country or region should be done in a manner appropriate for the local conditions. Nevertheless, we hope that our guidelines will be able to serve as a useful reference in the standardization of the diagnosis and treatment of FD in a wide variety of countries and regions.

Algorithm

Figure 1 shows the algorithm (flowchart) for the diagnosis and treatment of FD. The algorithm represents the consensus opinion of the members of the Guidelines Creating Committee and emphasizes strength of recommendation and level of evidence.