For Functional Dyspepsia Patients Research Articles

Clinical Efficacy and Mechanism of Transcutaneous Neuromodulation on Functional Dyspepsia.

Prokinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients, and the pathogenesis is still unclear. The purpose of this study was to investigate the therapeutic effect of transcutaneous neuromodulation (TN) on FD and its potential mechanisms. Fifty-seven FD patients were enrolled in the study and randomly divided into 3 groups (TN Neiguan (PC6) group, TN Zusanli (ST36) group, and sham TN group) that received corresponding treatment respectively for 4 weeks. Then, all the patients enrolled received TN PC6 combined with ST36 treatment for another 4 weeks. Dyspepsia symptom questionnaire, Medical outcomes study item short form health survey (SF-36), Hospital Anxiety and Depression Scale were used to assess the severity of symptoms. Gastric accommodation, gastric emptying rate, and related parameters of electrogastrogram were used to assess the pathophysiological mechanism of FD. The possible gastrointestinal hormonal mechanism involved was assessed by detecting serum ghrelin, neuropeptide Y, and vasoactive intestinal peptide. The possible duodenal inflammation mechanism involved was assessed by detecting duodenal mucosa. TN treatment reduced the dyspepsia symptom score ( P <0.05) and improved the quality of life. After TN treatment, the gastric accommodation ( P <0.01), the gastric emptying rate ( P <0.01), and the percentages of preprandial ( P <0.05) and postprandial ( P <0.05) gastric slow waves (GSW) were increased. The proportions of preprandial ( P <0.05) and postprandial ( P <0.05) gastric electrical rhythm disorder were reduced. The double acupoint combination therapy further enhanced the therapeutic effect of single acupoint. In addition, the levels of ghrelin ( P <0.001) and neuropeptide Y ( P <0.001) were significantly increased, the level of vasoactive intestinal peptide ( P <0.001) was significantly decreased, and the total number of mast cells ( P <0.001) in the duodenal bulb was significantly decreased after double acupoints combination therapy. TN treatment significantly improves the dyspepsia symptoms of FD patients and their quality of life. TN treatment increases the percentage of normal GSW, reduces the proportion of gastric electrical rhythm disorder, and improves the gastric accommodation and gastric emptying rate. The therapeutic effect of TN may be caused by regulating gastrointestinal hormone secretion and alleviating local inflammatory responses in duodenum. In addition, the improvement of TN on GSW was closely related to the decrease of bradygastria.

Prokinetics for the treatment of functional dyspepsia: an updated systematic review and network meta-analysis

BackgroundSince the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.MethodsAn updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.ResultsA total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.ConclusionsMetoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

Clinical-functional brain connectivity signature predicts longitudinal symptom improvement after acupuncture treatment in patients with functional dyspepsia.

Whilst acupuncture has been shown to be an effective treatment for functional dyspepsia (FD), its efficacy varies significantly among patients. Knowing beforehand how each patient responds to acupuncture treatment will facilitate the ability to produce personalized prescriptions, therefore, improving acupuncture efficacy. The objective of this study was to construct the prediction model, based on the clinical-neuroimaging signature, to forecast the individual symptom improvement of FD patients following a 4-week acupuncture treatment and to identify the critical predictive features that could potentially serve as biomarkers for predicting the efficacy of acupuncture for FD. Clinical-functional brain connectivity signatures were extracted from samples in the training-test set (100 FD patients) and independent validation set (60 FD patients). Based on these signatures and support vector machine algorithms, prediction models were developed in the training test set, followed by model performance evaluation and predictive features extraction. Subsequently, the external robustness of the extracted predictive features in predicting acupuncture efficacy was evaluated by the independent validation set. The developed prediction models possessed an accuracy of 88% in predicting acupuncture responders, as well as an R2 of 0.453 in forecasting symptom relief. Factors that contributed significantly to stronger responsiveness of patients to acupuncture therapy included higher resting-state functional connectivity associated with the orbitofrontal gyrus, caudate, hippocampus, and anterior insula, as well as higher baseline scores of the Symptom Index of Dyspepsia and shorter durations of the condition. Furthermore, the robustness of these features in predicting the efficacy of acupuncture for FD was verified through various machine learning algorithms and independent samples and remained stable in univariate and multivariate analyses. These findings suggest that it is both feasible and reliable to predict the efficacy of acupuncture for FD based on the pre-treatment clinical-neuroimaging signature. The established prediction framework will promote the identification of suitable candidates for acupuncture treatment, thereby improving the efficacy and reducing the cost of acupuncture for FD.

The Role of Medial Prefrontal Cortex in Acupuncture Treatment for Functional Dyspepsia.

Acupuncture is an effective therapy for functional dyspepsia (FD). However, the efficacy of acupuncture in the treatment of FD varies among individuals in clinical practice. This study aimed to reveal the brain response patterns in acupuncture higher response/lower response FD patients. Firstly, we performed a within-group comparison of brain function activity before and after acupuncture treatment in 115 FD patients and analyzed the correlation between brain function activity changes and clinical improvements. Secondly, 115 subjects were divided into the acupuncture higher response group or the lower response group based on the median clinical improvement values. The changes in functional brain activity after acupuncture treatment were investigated in these two groups, respectively. Finally, the identified brain regions associated with the clinical improvements were set as regions of interest (ROI), and the ROI-to-voxel functional connectivity comparisons were also performed in both groups, respectively. The results demonstrated that the functional activities of the left cerebellum inferior, right middle temporal gyrus, and right medial prefrontal cortex (mPFC) were increased, and the left Heschl and right middle cingulate cortex were decreased in 115 FD patients after acupuncture treatment. The functional connectivity changes of mPFC were correlated with improving the Nepean Dyspepsia Symptom Index. The significant increase in mPFC functional activity was also found in acupuncture higher response FD patients but not in lower response FD patients. The functional connectivity between the mPFC and default mode network (DMN) was significantly diminished in the higher response group but not in the lower response group. In conclusion, this study suggested that modulating the functional activity of the mPFC and its connectivity to the DMN may be one of the important mechanisms of acupuncture for treating FD with a higher response.

Predicting acupuncture efficacy for functional dyspepsia based on routine clinical features: a machine learning study in the framework of predictive, preventive, and personalized medicine.

Acupuncture is safe and effective for functional dyspepsia (FD), while its efficacy varies among individuals. Predicting the response of different FD patients to acupuncture treatment in advance and therefore administering the tailored treatment to the individual is consistent with the principle of predictive, preventive, and personalized medicine (PPPM/3PM). In the current study, the individual efficacy prediction models were developed based on the support vector machine (SVM) algorithm and routine clinical features, aiming to predict the efficacy of acupuncture in treating FD and identify the FD patients who were appropriate to acupuncture treatment. A total of 745 FD patients were collected from two clinical trials. All the patients received a 4-week acupuncture treatment. Based on the demographic and baseline clinical features of 80% of patients in trial 1, the SVM models were established to predict the acupuncture response and improvements of symptoms and quality of life (QoL) at the end of treatment. Then, the left 20% ofpatients in trial 1 and 193 patients in trial 2 were respectively applied to evaluate the internal and external generalizations of these models. These models could predict the efficacy of acupuncture successfully. In the internal test set, models achieved an accuracy of 0.773 in predicting acupuncture response and an R 2 of 0.446 and 0.413 in the prediction of QoL and symptoms improvements, respectively. Additionally, these models had well generalization in the independent validation set and could also predict, to a certain extent, the long-term efficacy of acupuncture at the 12-week follow-up. The gender, subtype of disease, and education level were finally identified as the critical predicting features. Based on the SVM algorithm and routine clinical features, this study established the models to predict acupuncture efficacy for FD patients. The prediction models developed accordingly are promising to assist doctors in judging patients' responses to acupuncture in advance, so that they could tailor and adjust acupuncture treatment plans for different patients in a prospective rather than the reactive manner, which could greatly improve the clinical efficacy of acupuncture treatment for FD and save medical expenditures. The online version contains supplementary material available at 10.1007/s13167-022-00271-8.

Acupuncture therapy with point selection based on syndrome differentiation along the meridians for functional dyspepsia: a randomized controlled trial

To observe the difference in clinical efficacy between acupuncture with point selection based on syndrome differentiation along the meridians and acupuncture at non-meridian and non-acupoint points for functional dyspepsia (FD). A total of 74 FD patients were randomized into an observation group and a control group, with 37 cases in each group. Both groups received acupuncture treatment. Zusanli (ST 36) and Neiguan (PC 6) were selected in the observation group, with Taichong (LR 3) and Neiting (ST 44) added for excess syndrome, and Gongsun (SP 4) and Yinlingquan (SP 9) added for deficiency syndrome. Four non-meridian and non-acupoint points were selected in the control group. The treatments in both groups were performed once a day with a 2-day break after 5 consecutive treatments, which constituted one treatment course. A total of 4 courses were performed. The scores of Nepean dyspepsia index (NDI) and Leeds dyspepsia questionnaire (LDQ) were recorded before and after treatment, and during follow-up (8, 12, 16, 20 and 24 weeks after recruitment) to assess the clinical efficacy. The NDI scores in the two groups after treatment and at each time point during follow-up were higher than those before treatment (all P<0.05), and the LDQ scores were lower than those before treatment (all P<0.05). The NDI scores after treatment and at each time point during follow-up in the observation group were higher than those in the control group (all P<0.01); the total LDQ score and scores of upper abdominal pain, postprandial satiety and upper abdominal burning sensation after treatment and at each time point during follow-up in the observation group were significantly lower than those in the control group (P<0.01 or P<0.05). Acupuncture with point selection based on syndrome differentiation along the meridians has a better curative effect than acupuncture at non meridian and non-acupoint points in the treatment of FD.

The participation of basolateral amygdala in the efficacy of acupuncture with deqi treating for functional dyspepsia.

Deqi is taken as an indispensable requirement to achieve acupuncture efficacy. This study aimed to explore the central influence of deqi on the efficacy of acupuncture for functional dyspepsia (FD). 70 FD patients were randomized to receive 20 sessions' acupuncture treatment with (n = 35) and without deqi (n = 35). In each group, 25 FD patients randomly selected underwent functional magnetic resonance imaging (fMRI) scans before and after treatment. After group re-division according to deqi response, changes of amygdala subregions-based resting-state functional connectivity (rsFC) were compared between the acupuncture with and without obvious deqi group. The clinical changes of the Nepean Dyspepsia Symptom Index (NDSI) measuring FD symptoms were also used to further assess the correlation with amygdala subregions rsFC in FD patients. The decrease in the NDSI scores (pre-pos) in the obvious deqi group was significantly greater than that in the acupuncture without obvious deqi group (p < 0.05). Compared to the without obvious deqi group, the obvious deqi group showed significantly decreased the left basolateral amygdala (BLA) rsFC with bilateral insular (INS), putamen and middle/posterior cingulate cortex (MCC/PCC), right pallidum and hippocampus (HIPP) after treatment. The changed NDSI scores(pre-post) of all 41 FD patients was significantly positively correlated with their Fisher's transformed z value of the left BLA rsFC with left INS (r = 0.376, FDR corrected p = 0.015), and rsFC with right HIPP (r = 0.394, FDR corrected p = 0.015). The changed NDSI scores(pre-post) of the obvious deqi group was significantly negatively correlated with their Fisher's transformed z value of the right centromedial amygdala (CMA) rsFC with left medial prefrontal cortex (mPFC) (r = -0.463, p = 0.035). The results tested the hypothesis that the advantage of deqi on efficacy is related to affecting the BLA and CMA rsFC. It suggested that deqi might influence the abnormal rsFC within the salience network (SN), and participate in the adaptive modulation of disrupted relationship between the SN and default mode network (DMN).

Efficacy Comparison of Different Acupuncture Treatments for Functional Dyspepsia: A Systematic Review with Network Meta-Analysis.

Background Acupuncture has been found to be an effective treatment for functional dyspepsia (FD). Currently, several types of acupuncture have been developed but it is not clear which type is suitable for FD. Currently, doctors often rely on experience to decide which form of acupuncture to apply. Herein, we employed network meta-analysis (NMA) to compare the effectiveness of various methods of acupuncture in the treatment of functional dyspepsia. Methods We searched for randomized controlled trials (RCTs) of acupuncture treatments for functional dyspepsia in seven databases; PubMed, the Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure (CNKI) database, Chinese Science and Technique Journals (CQVIP), and Chinese Biomedical Database (CBM) from the date of database inception to October 10, 2019. Cochrane risk of bias tool was used to analyze the risk of bias of the included RCTs. Pairwise meta-analyses were performed with RevMan 5.3 and the network meta-analysis of the included RCTs was performed using the frequentist framework. Results A total of 35 studies involving 3301 patients and 10 interventions were eligible for this study. NMA results showed that five types of acupuncture (manual acupuncture, acupoint application, moxibustion, acupoint catgut embedding, and warm acupuncture alone) all were superior to prokinetics (itopride, mosapride, and domperidone) and sham acupuncture in terms of improving the symptoms of functional dyspepsia. Specifically, manual acupuncture and electroacupuncture were more effective in improving the MOS 36 Item Short-Form Health Survey (SF-36) compared to itopride and sham acupuncture, and electroacupuncture was the best among the three acupuncture therapies (acupuncture, electroacupuncture, and acupoint catgut embedding). Moxibustion and manual acupuncture were more effective in improving Nepean Dyspepsia Life Quality Index (NDLQI) compared to itopride, domperidone, and sham acupuncture; moxibustion ranks first among the three acupuncture therapies (acupuncture, electroacupuncture, moxibustion). Conclusions These results showed that manual acupuncture alone was the most effective therapy for FD. It should, therefore, be considered as an alternative treatment for FD patients who are unresponsive to prokinetics or intolerant to the adverse effects of prokinetics. We recommend further multiple centers and high-quality RCT studies to confirm the present findings.

Electroacupuncture Upregulated Ghrelin in Rats with Functional Dyspepsia via AMPK/TSC2/Rheb-Mediated mTOR Inhibition

BackgroundGastrointestinal motility disorder is an important pathological basis for functional dyspepsia (FD). Epigastric ache and discomfort are the main symptoms of FD, and ghrelin deficiency is closely related to the occurrence and development of FD. While electroacupuncture (EA) alleviated the symptoms of FD patients and improved their quality of life, there is a lack of sufficient mechanistic evidence to support these beneficial effects.MethodsAn in vivo FD model was established in wild-type and mammalian target of rapamycin (mTOR) knockout (−/−) rats. FD rats were subjected to EA with or without mTOR agonists or inhibitors. Gastric emptying and intestinal propulsion were assessed, and pathological changes in the hypothalamus, gastric antrum, and small intestine were examined histologically. In addition, ghrelin expression and AMPK/TSC2/Rheb/mTOR activation were detected by quantitative reverse transcription polymerase chain reaction and western blot.ResultsEA alone or in combination with mTOR inhibitors improved gastrointestinal function in FD rats by increasing the rates of intestinal propulsion and gastric emptying, and pathological changes in the hypothalamus, gastric antrum, and small intestine were alleviated. This may be related to the significant upregulation of ghrelin expression and the effective activation of the AMPK/TSC2/Rheb/mTOR signaling pathway. Interestingly, EA also improved gastrointestinal function and ghrelin expression in mTOR (−/−) KO FD rats.ConclusionAltering the level of ghrelin by regulating AMPK/TSC2/Rheb-mediated mTOR inhibition is an important way through which EA treats FD. The complex EA-mediated regulatory mechanisms of the brain–gut axis still require further exploration.

Electroacupuncture plus on-demand gastrocaine for refractory functional dyspepsia: Pragmatic randomized trial.

Treatment options for functional dyspepsia (FD) refractory to pharmacological treatments are limited but the effectiveness of electroacupuncture (EA) is uncertain. We assessed the effectiveness of EA combined with on-demand gastrocaine. We conducted a single-center, assessor-blind, randomized parallel-group 2-arm trial on Helicobacter pylori negative FD patients of the postprandial distress syndrome subtype refractory to proton pump inhibitor, prokinetics, or H2 antagonists. Enrolled participants were block randomized in a 1:1 ratio, with concealed random sequence. The treatment and control groups both received on-demand gastrocaine for 12weeks, but only those in treatment group were offered 20 sessions of EA over 10weeks. The primary endpoint was the between-group difference in proportion of patients achieving adequate relief of symptoms at week 12. Of 132 participants randomly assigned to EA plus on-demand gastrocaine (n=66) or on-demand gastrocaine alone (n=66), 125 (94.7%) completed all follow-up at 12weeks. The EA group had a compliance rate 97.7%. They had a significantly higher likelihood in achieving adequate symptom relief at 12weeks, with a clinically relevant number needed to treat (NNT) value of 2.36 (95% CI: 1.74, 3.64). Among secondary outcomes, statistically and clinically significant improvements were observed among global symptom (NNT=3.85 [95% CI: 2.63, 7.69]); postprandial fullness and early satiation (NNT=5.00 [95% CI: 2.86, 25.00]); as well as epigastric pain, epigastric burning, and postprandial nausea (NNT=4.17 [95% CI: 2.56, 11.11]). Adverse events were minimal and nonsignificant. For refractory FD, EA provides significant, clinically relevant symptom relief when added to on-demand gastrocaine (ChiCTR-IPC-15007109).

Electroacupuncture for functional dyspepsia and the influence on serum Ghrelin, CGRP and GLP-1 levels

ObjectiveTo observe the clinical efficacy of electroacupuncture for functional dyspepsia (FD), and explore the corresponding mechanism. MethodsSixty-four FD patients were randomly divided into electroacupuncture group and western medicine group, with 32 cases in each group. In electroacupuncture group, electroacupuncture at Zúsānlĭ (足三里ST 36), Sānyīnjiāo (三阴交SP 6), Gōngsūn (公孙SP 4) and Nèiguān (内关PC 6) was performed for once a day, and the needles were retained for 30 min. In western medicine group, oral administration of mosapride citrate dispersible tablets in a dosage of 5 mg/time was carried out for 3 times a day. Treatment was conducted for 30 consecutive days in both groups. The scores of Leeds dyspepsia questionnaire (LDQ) and functional digestive disorder quality of life (FDDQL) of patients in both groups were recorded before and after treatment. Serum Ghrelin, CGRP and GLP-1 levels of patients were tested before and after treatment respectively, and the clinical efficacy of patients in both groups was evaluated after treatment. ResultsIn western medicine group, LDQ score after treatment was lower than that before treatment (P < 0.05), FDDQL score after treatment was higher than that before treatment, while the differences were not statistically significant (P > 0.05). LDQ score in electroacupuncture group after treatment was lower than that before treatment (P < 0.05), and also lower than that in western medicine group at the same time point (P < 0.05). FDDQL score in electroacupuncture group after treatment was higher than that before treatment (P < 0.05), and also higher than that in western medicine group at the same time point (P < 0.05). In western medicine group, Ghrelin level after treatment was higher than that before treatment (P < 0.05), CGRP level reduced, and the differences were not statistically significant (P > 0.05). GLP-1 level after treatment was also higher than that before treatment (P < 0.05). In electroacupuncture group, Ghrelin level after treatment was higher than that before treatment, CGRP level reduced, and GLP-1 level after treatment was also higher than that before treatment (both P < 0.05). According to the comparison of values of each index between electroacupuncture group and western medicine group after treatment, the differences were all statistically significant (all P < 0.05). The total effective rate in electroacupuncture group was 90.63% (29/32) which was higher than that in western medicine group 68.75%(22/32), and the differences were statistically significant (P < 0.05). ConclusionElectroacupuncture at ST 36, SP 6, SP 4 and PC 6 can effectively improve the clinical symptoms of FD patients, and the mechanism might be related with the increase of serum Ghrelin and GLP-1 levels and the decrease of serum CGRP level.

Impact of eating attitude and impairment of physical quality of life between tertiary clinic and primary clinic functional dyspepsia outpatients in Japan.

Background/AimsThere is no available data on factors associated with healthcare-seeking behavior for functional dyspepsia (FD) symptoms at either tertiary or primary clinics in Japan. Therefore, we aimed to compare clinical symptoms and life styles such as sleep disorders and eating attitude in FD patients visiting general practitioners at primary clinics with those consulting gastroenterologists at tertiary clinics to clarify healthcare-seeking patterns in Japanese patients.MethodsFifty-one FD outpatients in a tertiary clinic (college hospital), 50 FD outpatients visiting primary clinics and 50 healthy volunteers were enrolled. Clinical symptoms, quality of life, sleep disorders, eating attitude and anxiety were estimated using the Gastrointestinal Symptom Rating Scale (GSRS), Social Functioning-8 (SF-8) test, Pittsburg Sleep Quality Index (PSQI) test and State-Trait Anxiety Inventory (STAI) for FD outpatients and healthy volunteers.ResultsFD outpatients exhibited higher mean scores of GSRS than healthy volunteers. The SF-8 physical component summary scores in the tertiary clinic group were significantly lower than those in the primary clinic group. GSRS scores were significantly (P < 0.001, P = 0.002) associated with global PSQI scores in FD outpatients as well as with STAI-trait scores (P = 0.006, P = 0.001) compared to healthy volunteers. The frequency of eating between meals in the primary clinic group was significantly (P < 0.05) higher than that in the tertiary clinic group.ConclusionsIt may be important for clarification of healthcare-seeking behavior to determine the difference in both impairment of physical quality of life and eating attitudes between tertiary clinic and primary clinic FD outpatients in Japan.

The use of pictograms improves symptom evaluation by patients with functional dyspepsia.

No validated patient-reported outcome (PRO) measure exists for functional dyspepsia (FD) assessment. Verbal descriptions of different upper abdominal symptoms may be poorly distinguishable to patients. To investigate whether understanding of FD symptoms is enhanced by pictograms symbolising the nature of the symptoms, besides verbal descriptors. Consecutive FD patients were randomised to fill out a questionnaire assessing nineupper gastrointestinal symptoms (post-prandial fullness, early satiation, epigastric pain, epigastric burning, bloating centred in the upper abdomen, nausea, vomiting, heartburn, regurgitation) with or without accompanying pictograms. Symptoms were rated for frequency and severity (0-5), and patients also identified the most bothersome symptom. Subsequently, in-depth history was taken by an expert clinician, who filled out the same symptom ratings. Concordance between patient and clinician ratings was quantified using chi-square and kappa statistics. Content validity of pictograms was first confirmed by 15 FD patients. Next, 76 patients (52 women, age 42.2±1.9) were randomised to questionnaires with or without pictograms. The concordance with clinician's assessment as gold standard rose from 36 without to 48% for questions with pictograms (P<0.0001). Considering the Rome III subdivision, benefit in concordance with pictograms was present for post-prandial distress, epigastric pain syndrome and reflux symptoms. Kappa statistics confirmed these gains (weighted kappa values for concordance of symptom frequency ratings rose from 0.214 to 0.446 with pictograms), and also showed better concordance of the most bothersome symptom with pictograms. Pictograms accompanying verbal descriptors significantly improve concordance of functional dyspepsia symptom ratings by patients with evaluation by their physicians.

Clinical Classification of Subgroups According to the Rome III Criteria Cannot be Used to Distinguish the Associated Respective Pathophysiology in Japanese Patients with Functional Dyspepsia

Patients who meet the Rome III criteria for functional dyspepsia (FD) are generally classified into the following two subgroups, those with postprandial distress syndrome (PDS) and those with epigastric pain syndrome (EPS), in order to treat the dyspeptic symptoms caused by the respective pathophysiological conditions. However, whether simple classification of FD can accurately distinguish the pathophysiological differences between PDS and EPS remains to be clarified because the pathophysiology of FD is characterized and complicated by various factors. After classifying FD patients who were not receiving medication at the initial visit, we assessed and compared the following pathophysiological factors between the PDS and EPS groups: (1) the gastric reservoir and emptying functions using a radioisotope method (n=75), (2) the autonomic nervous system (ANS) function using electrocardiography (n=45), (3) gastric mucosal atrophy and intestinal metaplasia using histological examinations (n=47), (4) endoscopic findings of the stomach, such as superficial changes, abnormal gastroesophageal flap valves (n=67) and (5) Helicobacter pylori infection (n=48). The FD patients exhibited higher rates of an impaired reservoir function (49.3%), gastric emptying disorders (54.7%) and relative hyperactivity of the sympathetic nervous system (31.9%) than the control subjects. However, endoscopic and histological changes of the stomach were similar in both the FD patients and control subjects. In addition, no differences were observed in the above-mentioned factors between the PDS and EPS groups. The simple classification of FD patients into two subgroups according to the Rome III criteria following diagnosis does not indicate any differences in the pathophysiology related to the respective dyspeptic symptoms of FD patients.

Randomised clinical trial: the effects of amitriptyline on drinking capacity and symptoms in patients with functional dyspepsia, a double-blind placebo-controlled study

Functional dyspepsia is one of the most prevalent (15-40%) functional gastrointestinal disorders. Antidepressants such as amitriptyline are often used in these patients, but clinical studies are currently lacking. To evaluate the effect of 8 weeks of treatment with amitriptyline on drinking capacity, symptoms evoked by a standardised drink test (primary endpoint) and clinical symptoms (secondary endpoint). Patients meeting the Rome III criteria for functional dyspepsia (FD) were invited to participate in a double blind, randomised, placebo-controlled trial and were treated with either amitriptyline (12.5-50 mg) or placebo during 8 weeks. All included patients underwent a nutrient drink test before and after treatment. Drinking capacity and evoked symptoms were recorded. In addition, dyspeptic symptoms were weekly assessed using PAGI SYM (patient assessment of upper gastrointestinal symptom severity index) questionnaire. Thirty-eight patients (amitriptyline n=18, placebo n=20; age 41±2year, 61% F) completed the study. The drinking capacity of liquid meal was not affected by either amitriptyline or placebo treatment. Postprandial symptoms were not significantly different between amitriptyline and placebo. During the entire treatment, total symptom score (0.47 points, P=0.02) and nausea (0.86 points, P=0.004) on PAGI SYM were significantly reduced by amitriptyline compared with placebo. Amitriptyline did not affect drinking capacity and postprandial symptoms evoked by the drink test in FD patients. However, total clinical symptom score and nausea were reduced during 8 weeks of treatment. Our data suggest that amitriptyline particularly improves nausea in functional dyspepsia, but larger clinical trials are needed to further confirm our findings.

A Multicenter Open-Label Randomized Trial Comparing Rabeprazole Versus Itopride in Japanese Functional Dyspepsia: The NAGOYA Study

BACKGROUND&AIMS: The efficacy of proton pump inhibitor (PPI) for functional dyspepsia (FD) in Japan, in which the acid secretion is thought to be less than Western people, is unknown. The aims of this study was to compare the therapeutic effects of Rabeprazole (RPZ) and Itopride (ITO), and to investigate the randomized open-labeled trial in Japanese FD patients. METHODS: 151 consecutive patients diagnosed as FD by Rome III criteria, were randomly assigned to either 4-week treatment with RPZ or with ITO. Dyspeptic symptoms were evaluated with questionnaires, additional abdominal pain and indigestion score in Gastrointestinal Symptom Rating Scale as a FD symptom score (FD score) at pretreatment and 1, 2, and 4 weeks after the treatment. The efficacy endpoint is the change rates based on pretreatment in FD score at each time-points. We also conducted sub-analysis of epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). RESULTS: At all time-points, RPZ group was more higher improvement rates than ITO group significantly (Figure). RPZ group showed significant rapid improvement in FD score within 1 week, and persisted until after 4 weeks, but, significant improvement in FD score was only seen after 4 weeks with ITO. With RPZ improved FD symptoms in both EPS and PDS, significantly, whereas the significant improvement with ITO was only seen in PDS. CONCLUSIONS: These results showed that acid suppressive therapy with PPI is more useful than with PDS as well as with EPS in Japanese FD patients.

Gastroprokinetic effects of DA-9701, a new prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber

To develop a therapeutic for functional dyspepsia (FD), a prokinetic agent, DA-9701 has been newly formulated with Pharbitis Semen and Corydalis Tuber and we evaluated the gastroprokinetic effects of DA-9701 in comparison with conventional prokinetics. Oral administration with DA-9701 not only significantly accelerated gastric emptying in normal rats but also restored the delayed gastric emptying caused by apomorphine and cisplatin up to almost normal levels. For gastrointestinal transit, DA-9701 caused FITC-dextran to travel a significantly longer distance than the control, and in the delayed GI transit models induced by laparotomy and atopine, DA-9701 considerably increased the values of mean geometric center (MGC), while the conventional prokinetics rarely showed significant effects. Furthermore, DA-9701 drastically increased the gastric accommodation in Beagle dogs, shifting the pressure-volume curve toward considerably higher volume compared to the control, which was comparable to that of cisapride. These results indicate that DA-9701 has potential as a safe and effective therapeutic for FD patients with abnormalities in GI motor function.

Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia

An effective therapeutic strategy for functional dyspepsia (FD) has not been well-established. We investigated and compared the therapeutic effects of famotidine, mosapride and tandospirone for the control of dyspeptic symptoms. Fully examined FD patients of outpatient clinics at seven different medical centres were enrolled in the study. They were randomly assigned to three groups based on the type of drug administered: famotidine, mosapride and tandospirone. The effects of treatment over 4 weeks were assessed by visual analogue scales. All of the drugs showed beneficial effects, although famotidine was the most effective for symptom relief, which was significantly greater than tandospirone, while the effect of mosapride was similar to that of famotidine. No subtype of FD showed a better response to a particular type of drug. For the treatment of FD, famotidine demonstrated the best therapeutic effect, followed by mosapride, while that of tandospirone was significantly lower.

Maximum tolerated volume in drinking tests with water and a nutritional beverage for the diagnosis of functional dyspepsia

Recently, drinking load tests with water or nutritional beverages have been proposed as diagnostic tools for functional dyspepsia (FD), therefore we sought to reproduce if these tests can discriminate between FD patients and controls in a Mexican population. Twenty FD-Rome II patients were matched by age and gender with 20 healthy controls. All underwent both drinking tests at a 15 mL/min rate, randomly, 7 d apart. Every 5 min within each test, four symptoms were evaluated (satiety, bloating, nausea and pain) by Likert scales. Maximum tolerated volume (MTV) was defined as the ingested volume when a score of 5 was reached for any symptom or when the test had to be stopped because the patients could not tolerate more volume. Sensitivity and specificity were analyzed. FD patients had higher symptom scores for both tests compared to controls (water: t = 4.1, P = 0.001<0.01; Nutren: t = 5.2, P = 0.001<0.01). The MTV for water and Nutren were significantly lower in FD (water: 1 014+/-288 vs 1 749+/-275 mL; t = 7.9, P = 0.001<0.01; Nutren: 652+/-168 vs 1 278+/-286 mL; t = 6.7, P = 0.001<0.01). With the volume tolerated by the controls, the percentile 10 was determined as the lower limit for tolerance. Sensitivity and specificity were 0.90, 0.95 for water and 0.95, 0.95 for Nutren tests. A drinking test with water or a nutritional beverage can discriminate between FD patients and healthy subjects in Mexico, with high sensitivity and specificity. These tests could be used as objective, noninvasive, and safe diagnostic approaches for FD patients.