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Gastroparesis: An Evidence-Based Review for the Bariatric and Foregut Surgeon. Surg Obes Relat Dis 2023; 19:403-420. [PMID: 37080885 DOI: 10.1016/j.soard.2023.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023]
Abstract
Gastroparesis is a gastric motility disorder characterized by delayed gastric emptying. It is a rare disease and difficult to treat effectively; management is a dilemma for gastroenterologists and surgeons alike. We conducted a systematic review of the literature to evaluate current diagnostic tools as well as treatment options. We describe key elements in the pathophysiology of the disease, in addition to current evidence on treatment alternatives, including nutritional considerations, medical and surgical options, and related outcomes.
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Factors Associated With Placebo Treatment Response in Functional Dyspepsia Clinical Trials. Am J Gastroenterol 2022; 118:685-691. [PMID: 36729385 DOI: 10.14309/ajg.0000000000002097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/12/2022] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Controlling for potential placebo effects is an important aspect of gaining an accurate estimate of how much the therapy alone changes patient symptoms or other end points. When the placebo effect is large, this can lead to only a small fraction of changes seen in the active therapy group being attributed to the therapy itself. This problem has been well studied in some disorders of brain-gut interaction but not in functional dyspepsia where placebo response rates of 40% and higher have been reported. Understanding risk factors for placebo response might lead to changes in trial design that could reduce the magnitude of the problem. This study sought to identify risk factors for the placebo effect in a functional dyspepsia clinical trial with a longer-term aim of suggesting trial design changes that might minimize the problem. METHODS A secondary analysis of the clinical trial data was undertaken using 2 arms deemed to involve placebo therapy. Potential predictors were drawn from a wide range of patient characteristics including psychological, clinical, and physiological features. RESULTS Predictors of a stronger placebo effect on the gastrointestinal symptom rating scale included higher functional dyspepsia symptom burden at baseline (b = -0.101), coexisting irritable bowel syndrome (b = -0.436), and higher scores on the Nepean Dyspepsia Index eat/drink domain (-0.005). Baseline symptom burden and coexisting irritable bowel syndrome were found to be independent placebo predictors, explaining 13% of the variance in change in gastrointestinal symptom rating scale. Anxiety, childhood sexual abuse, sleep amount, and frequent abdominal pain were also found to be predictors of change in individual symptom scores. DISCUSSION The findings of this study yield actionable insights into trial methodology that may help to reduce the magnitude of the placebo effect in future functional dyspepsia treatment trials.
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Ho RS, Ho FF, Adams J, Cramer H, Leung B, Ward L, Zhang Y, Chung VC. Patients' perceptions on non-specific effects of acupuncture: Qualitative comparison between responders and non-responders. Integr Med Res 2022; 11:100771. [PMID: 34660196 PMCID: PMC8503627 DOI: 10.1016/j.imr.2021.100771] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 07/08/2021] [Accepted: 08/04/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Non-specific effect of acupuncture constitutes part of the overall effect generated via clinical encounter beyond needle insertion and stimulation. It is unclear how responders and non-responders of acupuncture experience non-specific effects differently. We aimed to compare their experiences in a nested qualitative study embedded in an acupuncture randomized trial on functional dyspepsia. METHODS Purposive sampling was used to capture experience of responders (n=15) and non-responders (n=15) to acupuncture via individual in-depth interviews. Design and analysis followed a framework analysis approach, with reference to an existing model on acupuncture non-specific effects. Themes emerging outside of this model were purposefully explored. RESULTS Responders had a more trusting relationship with acupuncturist in response to their expression of empathy. In turn they were more actively engaged in lifestyle modifications and dietary advice offered by acupuncturists. Non-responders were not satisfied with the level of reassurance regarding acupuncture safety. They were also expecting more peer support from fellow participants, regarded that as an empowerment process for initiating and sustaining lifestyle changes. CONCLUSIONS Our results highlighted key differences in acupuncture non-specific effect components experienced by responders and non-responders. Positive non-specific effects contributing to overall benefits could be enhanced by emphasizing on empathy expression from acupuncturists, trust-building, offering appropriate explanations on safety, and organizing patient support groups. Further research on the relative importance of each component is warranted.
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Affiliation(s)
- Robin S.T. Ho
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Fai Fai Ho
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Jon Adams
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
| | - Holger Cramer
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | - Brenda Leung
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
- Public Health, Faculty of Health Sciences, University of Lethbridge, Lethbridge, AB, Canada
| | - Lesley Ward
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
- Department of Sport, Exercise and Rehabilitation, Faculty of Life Sciences, Northumbria University, Newcastle Upon Tyne, UK
| | - Yan Zhang
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
- Harris College of Nursing and Health Sciences, Texas Christian University, Fort Worth, TX, USA
| | - Vincent C.H. Chung
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
- Australian Research Center in Complementary and Integrative Medicine, University Technology Sydney, Australia
- School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong
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Ho L, Zhong CC, Wong CH, Wu JC, Chan KK, Wu IX, Leung TH, Chung VC. Herbal medicine for functional dyspepsia: Network meta-analysis of placebo-controlled randomised trials. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114665. [PMID: 34592339 DOI: 10.1016/j.jep.2021.114665] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 08/06/2021] [Accepted: 09/19/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Conventional treatments for functional dyspepsia (FD) are limited. Herbal medicine (HM) use is prevalent despite unclear comparative effectiveness among different formulae. AIM OF THE STUDY This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of HM formulae for FD against placebo. MATERIALS AND METHODS Seven international and Chinese databases were searched for randomised controlled trials (RCTs) on HM versus placebo. Risk of bias among RCTs was assessed using Cochrane Risk-of-Bias Tool 2. Data from RCTs were extracted for random-effect pairwise meta-analyses. NMAs were performed to evaluate the comparative effectiveness of HM formulae. GRADE partially contextualised framework was adopted to facilitate NMA result interpretation. RESULTS Twelve different HM formulae were identified from fifteen RCTs of mediocre quality. At 8-week follow-up, pairwise meta-analyses indicated that HM was superior to placebo in alleviating global symptoms (pooled risk difference (RD): 0.20; 95% confidence interval (CI): 0.11-0.29), with effect size larger than the minimally clinically important difference of 0.20 RD. Sensitivity analysis showed no significant impact on results attributable to risk of bias. NMAs demonstrated that Xiao Yao Pill and Modified Ban Xia Xie Xin Decoction probably have a large beneficial effect on alleviating global symptoms (RD: 0.37; 95% CI: 0.03-0.99) and postprandial fullness (standardised mean difference: -0.93; 95% credible interval: -1.61 to -0.06), respectively. No serious adverse events were reported. CONCLUSIONS Xiao Yao Pill and Modified Ban Xia Xie Xin Decoction may be considered as an alternative among patients unresponsive to conventional treatments. The comparative effectiveness of these two formulae should be evaluated in future trials.
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Affiliation(s)
- Leonard Ho
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Claire Cw Zhong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Charlene Hl Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Justin Cy Wu
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Karina Kh Chan
- United Christian Nethersole Community Health Service - The Chinese University of Hong Kong Chinese Medicine Clinic Cum Training and Research Centre (Tai Po District), Hong Kong.
| | - Irene Xy Wu
- Xiangya School of Public Health, Central South University, Hunan, China.
| | - Ting Hung Leung
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Vincent Ch Chung
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
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Kim YH, Kim JY, Kwon OJ, Jung SY, Joung JY, Yang CS, Lee JH, Cho JH, Son CG. Efficacy of a Traditional Herbal Formula, Banha-Sasim-Tang in Functional Dyspepsia Classified as Excess Pattern. Front Pharmacol 2021; 12:698887. [PMID: 34512334 PMCID: PMC8429799 DOI: 10.3389/fphar.2021.698887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved "fullness after eating" index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit. Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013.
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Affiliation(s)
- Yun Hee Kim
- Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jun Young Kim
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - O-Jin Kwon
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - So Young Jung
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jin-Yong Joung
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Chang Sop Yang
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jun-Hwan Lee
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jung-Hyo Cho
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Chang-Gue Son
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
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Wang J, Gu S, Qin B. Efficacy of Helicobacter pylori eradication therapy for treatment of functional dyspepsia: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e26045. [PMID: 34011117 PMCID: PMC8136982 DOI: 10.1097/md.0000000000026045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 05/04/2021] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE The effect of Helicobacter pylori (H pylori) eradication therapy in functional dyspepsia (FD) patients was inconsistent in previously published randomized controlled trials. Therefore, we performed a comprehensive protocol for systematic review and meta-analysis in order to assess whether H pylori eradication therapy benefits patients with FD. METHODS In this systematic review and meta-analysis, we will search Web of Science, Embase, PubMed, Wanfang Data, Medline, Science Direct, Cochrane Library through April, 2021. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Data extraction was performed independently and only randomized clinical trials were included in this study. The risk of bias assessment was performed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions. All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom). RESULTS We hypothesized that H pylori eradication therapy compared to no eradication therapy has a statistically significant benefit for symptom relief and can also reduce the development of peptic ulcer disease. CONCLUSION This study expects to provide credible and scientific evidence for the efficacy of H pylori eradication therapy for patients with FD. OSF REGISTRATION NUMBER 10.17605/OSF.IO/4EHRB.
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Chung VC, Wong CH, Wu IX, Ching JY, Cheung WK, Yip BH, Chan KL, Cheong PK, Wu JC. Electroacupuncture plus on-demand gastrocaine for refractory functional dyspepsia: Pragmatic randomized trial. J Gastroenterol Hepatol 2019; 34:2077-2085. [PMID: 31117149 DOI: 10.1111/jgh.14737] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 05/14/2019] [Accepted: 05/19/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM 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. METHODS 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 12 weeks, but only those in treatment group were offered 20 sessions of EA over 10 weeks. The primary endpoint was the between-group difference in proportion of patients achieving adequate relief of symptoms at week 12. RESULTS 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 12 weeks. The EA group had a compliance rate 97.7%. They had a significantly higher likelihood in achieving adequate symptom relief at 12 weeks, 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. CONCLUSION For refractory FD, EA provides significant, clinically relevant symptom relief when added to on-demand gastrocaine (ChiCTR-IPC-15007109).
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Affiliation(s)
- Vincent Ch Chung
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong.,School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Charlene Hl Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Irene Xy Wu
- Xiang-Ya School of Public Health, Central South University, Chang-Sha, Hu-Nan, China
| | - Jessica Yl Ching
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - William Kw Cheung
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Benjamin Hk Yip
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Kam Leung Chan
- School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Pui Kuan Cheong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Justin Cy Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
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Luo L, Du L, Shen J, Cen M, Dai N. Benefit of small dose antidepressants for functional dyspepsia: Experience from a tertiary center in eastern China. Medicine (Baltimore) 2019; 98:e17501. [PMID: 31593119 PMCID: PMC6799471 DOI: 10.1097/md.0000000000017501] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.
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Affiliation(s)
- Liang Luo
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Lijun Du
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Jinhua Shen
- Department of Gastroenterology, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Mengsha Cen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Ning Dai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou
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Chung VCH, Wong CHL, Ching JYL, Sun WZ, Ju YL, Hung SS, Lin WL, Leung KC, Wong SYS, Wu JCY. Electroacupuncture plus standard of care for managing refractory functional dyspepsia: protocol of a pragmatic trial with economic evaluation. BMJ Open 2018; 8:e018430. [PMID: 29593017 PMCID: PMC5875645 DOI: 10.1136/bmjopen-2017-018430] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION This trial proposes to compare the effectiveness and cost-effectiveness of electroacupuncture (EA) plus on-demand gastrocaine with waiting list for EA plus on-demand gastrocaine in providing symptom relief and quality-of-life improvement among patients with functional dyspepsia (FD). METHODS AND ANALYSIS This is a single-centre, pragmatic, randomised parallel-group, superiority trial comparing the outcomes of (1) EA plus on-demand gastrocaine group and (2) waiting list to EA plus on-demand gastrocaine group. 132 (66/arm) endoscopically confirmed, Helicobacter pylori-negative patients with FD will be recruited. Enrolled patients will respectively be receiving (1) 20 sessions of EA over 10 weeks plus on-demand gastrocaine; or (2) on-demand gastrocaine and being nominated on to a waiting list for EA, which entitles them 20 sessions of EA over 10 weeks after 12 weeks of waiting. The primary outcome will be the between-group difference in proportion of patients achieving adequate relief of symptoms over 12 weeks. The secondary outcomes will include patient-reported change in global symptoms and individual symptoms, Nepean Dyspepsia Index, Nutrient Drink Test, 9-item Patient Health Questionnaire (PHQ9), and 7-item Generalised Anxiety Disorder Scale (GAD7). Adverse events will be assessed formally. Results on direct medical costs and on the EuroQol (EQ-5D) questionnaire will also be used to assess cost-effectiveness. Analysis will follow the intention-to-treat principle using appropriate univariate and multivariate methods. A mixed model analysis taking into account missing data of these outcomes will be performed. Cost-effectiveness analysis will be performed using established approach. ETHICS AND DISSEMINATION The study is supported by the Health and Medical Research Fund, Government of the Hong Kong Special Administrative Region of China. It has been approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee. Results will be published in peer-reviewed journals and be disseminated in international conference. TRIAL REGISTRATION NUMBER ChiCTR-IPC-15007109; Pre-result.
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Affiliation(s)
- Vincent C H Chung
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Charlene H L Wong
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Jessica Y L Ching
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Wai Zhu Sun
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Yan Li Ju
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Sheung Sheung Hung
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Wai Ling Lin
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Ka Chun Leung
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Samuel Y S Wong
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Justin C Y Wu
- Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong
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Herrick LM, Camilleri M, Schleck CD, Zinsmeister AR, Saito YA, Talley NJ. Effects of Amitriptyline and Escitalopram on Sleep and Mood in Patients With Functional Dyspepsia. Clin Gastroenterol Hepatol 2018; 16:401-406.e2. [PMID: 29199141 DOI: 10.1016/j.cgh.2017.10.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 10/07/2017] [Accepted: 10/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Tricyclic antidepressants are effective in reducing symptoms of functional dyspepsia (FD). We performed a post hoc analysis of data from a previous randomized clinical trial to determine whether the benefits of an antidepressant on gastrointestinal symptoms in patients with FD were mediated by improving sleep or reducing anxiety. We explored the relationships between psychological measures, quality of sleep, and relief of symptoms. METHODS We analyzed data from a multicenter, double-blind trial that evaluated the efficacy of antidepressants on symptoms of FD, from October 2006 through October 2012. Patients (n = 292) were randomly assigned to groups given 50 mg amitriptyline, 10 mg escitalopram, or placebo for 12 weeks. During the study, participants completed the following validated psychological questionnaires: Symptom Check List 90, Symptom Somatic Checklist, Hospital Anxiety Depression Scale, Profile of Mood States, State Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index at baseline and 12 weeks following treatment. RESULTS Baseline scores for the psychological and sleep measures were similar among groups; after 12 weeks there were no significant differences in scores among groups. Baseline mean global Pittsburgh Sleep Quality Index scores indicated poor sleep quality in all groups at baseline and after 12 weeks. Overall, antidepressants affected sleep duration scores: patients given amitriptyline had lower (better) scores than patients given placebo or escitalopram (P = .019). In all groups, responders had decreased anxiety and improvements in some sleep components. CONCLUSIONS In a post hoc analysis of data from a clinical trial that evaluated the effects of antidepressants in patients with FD, amitriptyline was found to reduce symptoms of FD, but its mechanism is unlikely to involve reductions in psychological distress. The drug may modestly improve sleep. Clinicaltrials.gov no: NCT00248651.
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Affiliation(s)
- Linda M Herrick
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Cathy D Schleck
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Alan R Zinsmeister
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Yuri A Saito
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Nicholas J Talley
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
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11
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Lacy BE, Saito YA, Camilleri M, Bouras E, DiBaise JK, Herrick LM, Szarka LA, Tilkes K, Zinsmeister AR, Talley NJ. Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia. Am J Gastroenterol 2018; 113:216-224. [PMID: 29257140 DOI: 10.1038/ajg.2017.458] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 10/09/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.
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Affiliation(s)
- B E Lacy
- Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Y A Saito
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - M Camilleri
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - E Bouras
- Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - J K DiBaise
- Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - L M Herrick
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - L A Szarka
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - K Tilkes
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - A R Zinsmeister
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - N J Talley
- Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia
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Lv L, Wang FY, Ma XX, Li ZH, Huang SP, Shi ZH, Ji HJ, Bian LQ, Zhang BH, Chen T, Yin XL, Tang XD. Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study. World J Gastroenterol 2017; 23:5589-5601. [PMID: 28852318 PMCID: PMC5558122 DOI: 10.3748/wjg.v23.i30.5589] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 05/12/2017] [Accepted: 06/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME III criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2:1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 °C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.
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Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial. Am J Gastroenterol 2017; 112:903-909. [PMID: 28291238 DOI: 10.1038/ajg.2017.52] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 12/01/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.
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Editorial: Functional Dyspepsia Treatment: Trials and Tribulations of Targeted Strategies. Am J Gastroenterol 2017; 112:910-912. [PMID: 28572654 DOI: 10.1038/ajg.2017.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 03/14/2017] [Indexed: 12/11/2022]
Abstract
While functional dyspepsia (FD) is an exceedingly common disorder, the number of treatment options remains limited, and strategies for the individualized implementation of these therapies largely are lacking. In the current issue of American Journal of Gastroenterology, Saito and colleagues report on a secondary analysis of data from the Functional Dyspepsia Treatment Trial, specifically examining the role of two candidate genetic markers in predicting FD response to antidepressant treatments. Though the current study yielded a negative result, it nevertheless emphasizes the importance of our continued pursuit of therapeutic biomarkers in order to move beyond "one-size-fits-all" approaches to the treatment of FD and related disorders.
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Herrick LM, Locke GR, Schleck CD, Zinsmeister AR, Treder V, Talley NJ. Dyspepsia in the community: value of a community-based mailed survey to identify potential participants for a randomized clinical trial. Scand J Gastroenterol 2015; 50:959-64. [PMID: 25761431 PMCID: PMC4655586 DOI: 10.3109/00365521.2014.980317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To assess the usefulness of a community-based mailed survey to identify participants with functional dyspepsia (FD) for a clinical trial. MATERIAL AND METHODS In 2008, a valid self-report questionnaire of gastrointestinal symptoms required for diagnosis of FD was mailed to randomly selected cohorts of Olmsted County, Minnesota, residents. From survey responses (54%), FD cases and controls were identified. Phone calls were completed in 2010 and 2011 to 54% of respondents offering participation to those meeting criteria. RESULTS Of 937 people identified from the survey, 189 cases and 265 controls were contacted by phone using four questions similar to the written survey resulting in a moderate level of agreement (Kappa 0.43, 95% CI: 0.35- 0.51; p = 0.11). The proportion reporting FD symptoms by survey was 42%, while the proportion by phone was 38%. Comparing classification of cases and controls, 118 (62%) survey cases had dyspepsia symptoms on phone screening while 53 (20%) of the survey controls reported FD symptoms. Of 171 who had symptoms, 60 (35%) declined, 33 (19%) were over study age limit, 24 (14%) had inadequate symptom levels and 36 (21%) had comorbidities. Of survey respondents contacted, six (3%) people were enrolled with two screen fails resulting in four (1%) randomized. CONCLUSION Agreement between survey and phone questions was modest. Classifications between case and control changed. People eligible and willing to participate were a fraction of people reporting symptoms. People participating in clinical trials do not broadly represent those in the population.
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Affiliation(s)
- Linda M. Herrick
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Cathy D. Schleck
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | | | - Vickie Treder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Nicholas, J. Talley
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia
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16
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Talley NJ, Locke GR, Saito YA, Almazar AE, Bouras EP, Howden CW, Lacy BE, DiBaise JK, Prather CM, Abraham BP, El-Serag HB, Moayyedi P, Herrick LM, Szarka LA, Camilleri M, Hamilton FA, Schleck CD, Tilkes KE, Zinsmeister AR. Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study. Gastroenterology 2015; 149:340-9.e2. [PMID: 25921377 PMCID: PMC4516571 DOI: 10.1053/j.gastro.2015.04.020] [Citation(s) in RCA: 232] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Revised: 03/13/2015] [Accepted: 04/16/2015] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.
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Affiliation(s)
- Nicholas J. Talley
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN,Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | | | - Yuri A. Saito
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Ann E. Almazar
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | | | - Brian E. Lacy
- Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - John K. DiBaise
- Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ
| | | | - Bincy P. Abraham
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX
| | - Hashem B. El-Serag
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX
| | - Paul Moayyedi
- Gastroenterology, McMaster University, Hamilton, ON, Canada
| | | | | | | | | | - Cathy D. Schleck
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
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Kim SE. Medical treatment of functional dyspepsia. KOSIN MEDICAL JOURNAL 2015. [DOI: 10.7180/kmj.2015.30.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Functional dyspepsia (FD) is a condition in which upper abdominal symptoms, such as epigastralgia, postprandial discomfort, and bloating, occur in the absence of any organic or metabolic disease that could explain the symptoms. The prevalence of FD is increasing, presumably because of an increasingly stressful environment, as well as overlap with other motility disorders such as gastroesophageal reflux diseases and irritable bowel syndrome. Numerous studies have attempted to determine the pathophysiological mechanisms of FD and establish effective FD treatment, with little success. Several therapeutic options have been explored, including Helicobacter pylori eradication, proton pump inhibitors, prokinetic agents, anti-depressant and anxiolytic agents, and acotiamide, a recent emerging drug. Through the many trials evaluating the efficacy of drugs for FD treatment, we found that it is necessary to treat according to the symptoms of FD and to use a combination of therapeutic options. Additional well-designed, prospective studies are needed to confirm the management of FD.
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Talley NJ, Holtmann G, Walker MM. Therapeutic strategies for functional dyspepsia and irritable bowel syndrome based on pathophysiology. J Gastroenterol 2015; 50:601-13. [PMID: 25917563 DOI: 10.1007/s00535-015-1076-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 02/06/2023]
Abstract
Functional gastrointestinal disorders (FGIDs) are common and distressing. They are so named because a defined pathophysiology in terms of structural or biochemical pathways is lacking. Traditionally FGIDs have been conceptualized as brain-gut disorders, with subgroups of patients demonstrating visceral hypersensitivity and motility abnormalities as well as psychological distress. However, it is becoming apparent that there are certain structural or biochemical gut alterations among subsets with the common FGIDs, most notably functional dyspepsia (FD) and irritable bowel syndrome (IBS). For example, a sodium channel mutation has been identified in IBS that may account for 2 % of cases, and subtle intestinal inflammation has been observed in both IBS and FD. Other research has implicated early life events and stress, autoimmune disorders and atopy and infections, the gut microbiome and disordered mucosal immune activation in patients with IBS or FD. Understanding the origin of symptoms in FGIDs will allow therapy to be targeted at the pathophysiological changes, not at merely alleviating symptoms, and holds hope for eventual cure in some cases. For example, there are promising developments in manipulating the microbiome through diet, prebiotics and antibiotics in IBS, and testing and treating patients for Helicobacter pylori infection remains a mainstay of therapy in patients with dyspepsia and this infection. Locally acting drugs such as linaclotide have been an advance in treating the symptoms of constipation-predominant IBS, but do not alter the natural history of the disease. A role for a holistic approach to patients with FGIDs is warranted, as brain-to-gut and gut-to-brain pathways appear to be activated.
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Affiliation(s)
- Nicholas J Talley
- Global Research, University of Newcastle, HMRI Building, Room 3419, Kookaburra Circuit, New Lambton, NSW, 2305, Australia,
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Pasalar M, Choopani R, Mosaddegh M, Kamalinejad M, Mohagheghzadeh A, Fattahi MR, Ghanizadeh A, Bagheri Lankarani K. Efficacy and safety of jollab to treat functional dyspepsia: a randomized placebo-controlled clinical trial. Explore (NY) 2015; 11:199-207. [PMID: 25777290 DOI: 10.1016/j.explore.2015.02.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is a common gastrointestinal disease that is highly prevalent worldwide. Because of its heterogeneous pathophysiology, treatment options for FD can be difficult to choose; in this context, complementary and alternative medicine modalities have been suggested as promising options. AIM To evaluate the efficacy of a traditional Persian medicine, jollab, in reducing patients' FD symptoms. METHODS In a double-blind randomized clinical trial, 160 patients with a diagnosis of FD were enrolled and treated with either jollab or placebo (15ml, t.i.d., four weeks, orally). The outcomes reported were changes in symptom frequency and severity as recorded in patients' diaries and evaluated with the Short Form of the Leeds Dyspepsia Questionnaire (SF-LDQ), and physical examination. RESULTS The response rate was higher in the treatment group (78%) than in the placebo group (31%) according to per-protocol sample analysis (P < .001). Symptoms of FD disappeared significantly more frequently, and the rate of concomitant synthetic drug consumption was significantly lower, in the jollab group compared to the placebo group at the end of the trial. Mean total symptom frequency and severity according to the SF-LDQ score was 1.55 ± 2.78 in the treatment group versus 5.61 ± 3.80 in the placebo group at the last follow-up time point (P < .001). A promising safety profile for jollab was observed throughout the trial. CONCLUSIONS In patients with FD, jollab appeared to be more effective than the placebo. Complementary and alternative therapies such as the use of this traditional medicinal substance may be beneficial in relieving symptoms of dyspepsia [ACTRN12613000584730].
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Affiliation(s)
- Mehdi Pasalar
- School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Vali Asr Ave., Tehran, Iran.
| | - Rasool Choopani
- School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Vali Asr Ave., Tehran, Iran
| | - Mahmoud Mosaddegh
- Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Kamalinejad
- Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdolali Mohagheghzadeh
- Department of Traditional Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Ghanizadeh
- Research Center for Psychiatry and Behavioral Sciences, Shiraz University of Medical Sciences, Hafez Hospital, Shiraz, Iran
| | - Kamran Bagheri Lankarani
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Health Policy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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20
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Yang CY, Huang HB, Peng DG. Efficacy of mosapride and pantoprazole in treatment of children with functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2015; 23:1989-1993. [DOI: 10.11569/wcjd.v23.i12.1989] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the efficacy and safety of mosapride and pantoprazole in the treatment of children with functional dyspepsia.
METHODS: Sixty children with functional dyspepsia were selected and randomly divided into either an observation group or a control group, with 30 cases in each group. Subjects in the observation group were treated with mosapride (5 mg, po, tid). Subjects in the control group were treated with pantoprazole (40 mg, po, qd). After 2 wk of treatment, the symptom score and clinical efficacy of the two groups were observed and compared.
RESULTS: After treatment, the scores of total symptoms, abdominal fullness after meals, early satiety, epigastric pain, and epigastric burning sensation in the two groups were significantly lower than those before the treatment (observation group: 14.39 ± 7.13 vs 20.79 ± 11.36, 4.39 ± 1.37 vs 4.84 ± 5.16, 3.89 ± 1.19 vs 4.17 ± 4.43, 3.74 ± 1.05 vs 6.37 ± 5.36, 3.95 ± 1.98 vs 6.73 ± 6.21; control group: 13.57 ± 6.42 vs 20.68 ± 11.41, 3.27 ± 1.16 vs 4.91 ± 5.21, 3.16 ± 1.08 vs 4.20 ± 4.52, 4.29 ± 1.23 vs 6.29 ± 5.83, 4.17 ± 1.54 vs 6.82 ± 6.08; P < 0.05 for all). The scores of total symptoms, abdominal fullness after meals, early satiety, epigastric pain, and epigastric burning sensation after treatment showed no significant differences between the two groups (P > 0.05 for all). The difference in the total response rate between the two groups was not statistically significant (70.00% vs 66.67%, P > 0.05). There were no significant differences in the response rates for postprandial distress syndrome and epigastric pain syndrome between the two groups (70.59% vs 64.71%, 69.23% vs 69.23%, P > 0.05 for both).
CONCLUSION: Both mosapride and pantoprazole have good efficacy in the treatment of children with functional dyspepsia.
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Pasalar M, Choopani R, Mosaddegh M, Kamalinejad M, Mohagheghzadeh A, Fattahi MR, Zarshenas MM, Jafari P, Lankarani KB. Efficacy of jollab in the treatment of depression in dyspeptic patients: a randomized double-blind controlled trial. J Evid Based Complementary Altern Med 2015; 20:104-108. [PMID: 25587004 DOI: 10.1177/2156587214563542] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The current study aimed to evaluate the efficacy of jollab, a well-known beverage from traditional Persian medicine in the treatment of depression among patients suffering from functional dyspepsia. In a randomized, double-blind, placebo-controlled trial, a pair of 80 patients were enrolled in 2 parallel groups as Jollab and placebo. The Beck Depression Inventory-II questionnaire was used for the assessment. At all, 133 patients enrolling in the treatment and placebo groups ended the protocol. According to the outcomes, changes in scores between the 2 groups were statistically significant at the end of trial (P ≤ .001). Taken as a whole, treatment group was significantly more effective than the placebo. Focusing on nutritional and pharmaceutical properties, jollab may be introduced not only as a medication for depression and allied ailment but also a pleasant daily drink.
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Affiliation(s)
- Mehdi Pasalar
- The School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rasool Choopani
- The School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahmoud Mosaddegh
- Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Kamalinejad
- Department of Pharmacognosy, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdolali Mohagheghzadeh
- Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad M Zarshenas
- Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Peyman Jafari
- Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran
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Guo QX, Peng N, Lv F, Jiang QH. Deanxit improves anxiety and depression in patients with functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2015; 23:324-327. [DOI: 10.11569/wcjd.v23.i2.324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the clinical effects of flupentixol and melitracen tablets (Deanxit) in the treatment of functional dyspepsia (FD).
METHODS: One hundred and ten patients with FD treated at our hospital from November 2012 to May 2014 were randomly divided into either an observation group or a control group, with 55 cases in each group. The control group was given conventional basic therapy, and the observation group was given Deanxit on the basis of conventional therapy. Treatment satisfaction, mental status, and clinical results were compared for the two groups.
RESULTS: After treatment, the observation group had a significantly higher rate of patient satisfaction than the control group with (92.7% vs 83.6%, P < 0.05). Self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) score were significantly lower in the observation group than in the control group (P < 0.05). The total effective rate was significantly higher in the observation group than in the control group (85.45% vs 54.55%, P < 0.05).
CONCLUSION: Deanxit can effectively improves anxiety and depression in patients with FD.
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Stein B, Everhart KK, Lacy BE. Treatment of functional dyspepsia and gastroparesis. ACTA ACUST UNITED AC 2014; 12:385-97. [PMID: 25169218 DOI: 10.1007/s11938-014-0028-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OPINION STATEMENT Functional dyspepsia (FD) and gastroparesis (GP) are the two most prevalent gastric neuromuscular disorders. These disorders are frequently confused, have more similarities than differences, and can be thought of as two ends of a continuous spectrum of gastric neuromuscular disorders (Fig. 1). FD is currently defined by the Rome III criteria; it is now subdivided into a pain-predominant subtype (epigastric pain syndrome) and a meal-associated subtype (post-prandial distress syndrome). GP is defined by symptoms in conjunction with delayed gastric emptying in the absence of mechanical obstruction. Symptoms for both FD and GP are similar and include epigastric pain or discomfort, early satiety, bloating, and post-prandial nausea. Vomiting can occur with either diagnosis; it is typically more common in GP. A patient suspected of having either FD or GP should undergo upper endoscopy. In suspected FD, upper endoscopy is required to exclude an alternative organic cause for the patient's symptoms; however, most (70 %) patients with dyspeptic symptoms will have FD rather than an organic disorder. In suspected GP, upper endoscopy is required to rule out a mechanical obstruction. A 4-hour solid-phase gastric emptying scan is recommended to confirm the diagnosis of GP; its utility is unclear in patients with FD, as it may not change treatment. Once the diagnosis of FD or GP is made, treatment should focus on the predominant symptom. This is especially true in patients with GP, as accelerating gastric emptying with the use of prokinetics may not necessarily translate into an improvement in symptoms. Unfortunately, no medication is currently approved for the treatment of FD and, thus, technically, all treatment options remain off-label, including medications for visceral pain (e.g., tricyclic antidepressants) and nausea. This review focuses on treatment options for FD and GP with an emphasis on new advances in the field over the last several years.
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Affiliation(s)
- Benjamin Stein
- Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA,
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Yang ZY. Efficacy and safety of pantoprazole sodium enteric-coated tablets combined with mosapride in treatment of functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2014; 22:4514-4518. [DOI: 10.11569/wcjd.v22.i29.4514] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy and safety of pantoprazole sodium enteric-coated tablets (Pan) combined with mosapride citrate tablets (Mosa) in the treatment of functional dyspepsia (FD).
METHODS: This was a prospective parallel controlled trial. One hundred and forty-nine FD patients were randomly divided into either an observation group (n = 75) or a control group (n = 74). The observation group was given Mosa plus Pan, and the control group was given Maso alone. Clinical effects were compared for the two groups.
RESULTS: The total response rate was significantly higher in the observation group than in the control group (96% vs 83.78%, χ2 = 6.1398, P = 0.0132). The incidence of adverse reactions was significantly lower in the observation group than in the control group (16% vs 29.73%, χ2 = 3.9868, P = 0.0459). The recurrence rates at 1, 3 and 6 mo were lower in the observation group than in the control group (8.0% vs 9.46%, 17.33% vs 21.62%, 24% vs 41.89%, and the difference at 6 mo was significant (χ2 = 5.4025, P = 0.0201). At 1, 3 and 6 mo, the functional digestive disorder quality of life questionnaire (FDDQL) scores and scale total scores were significantly higher in the observation group than in the control group (P < 0.05).
CONCLUSION: Pan combined with Mosa has better curative effect and higher safety than Mosa alone in the treatment of FD.
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Abstract
Dyspepsia is a complex disorder with several distinct pathophysiologic mechanisms that are still poorly understood. Patients who experience dyspepsia have a high burden of disease, with significant personal and economic costs. Although serious pathology presenting as dyspepsia is rare, clinicians need to be aware of alarm features that should trigger prompt referral for subspecialty care. Those without alarm features can be managed in a rational way with either empiric antisecretory therapy, test-and-treat for H pylori eradication, antidepressants, and psychotherapy, or a combination of these. Given the heterogeneity of symptoms and large variability in response to different treatments, more research into specific pathophysiologic mechanisms will likely help guide diagnosis and treatment choices in the future.
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Affiliation(s)
- Maryann Katherine Overland
- Division of General Internal Medicine, Primary Care Clinic, VA Puget Sound Health Care System, University of Washington, 1660 South Columbian Way, Seattle, WA 98108, USA.
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Sebastián-Domingo JJ. La medicina integrativa en el manejo de la dispepsia funcional. Papel del preparado herbal STW5. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:256-61. [DOI: 10.1016/j.gastrohep.2013.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 09/30/2013] [Accepted: 10/08/2013] [Indexed: 02/07/2023]
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Kwon YS, Son M. DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia. Biomol Ther (Seoul) 2013; 21:181-9. [PMID: 24265862 PMCID: PMC3830115 DOI: 10.4062/biomolther.2012.096] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Revised: 03/12/2013] [Accepted: 03/14/2013] [Indexed: 12/17/2022] Open
Abstract
Motilitone® (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments.
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Affiliation(s)
- Yong Sam Kwon
- Dong-A ST Research Institute, Yongin 446-905, Republic of Korea
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Kim JB, Shin JW, Kang JY, Son CG, Kang W, Lee HW, Lee DS, Park YC, Cho JH. A traditional herbal formula, Hyangsa-Pyeongwi san (HPS), improves quality of life (QoL) of the patient with functional dyspepsia (FD): randomized double-blinded controlled trial. JOURNAL OF ETHNOPHARMACOLOGY 2013; 151:279-286. [PMID: 24239600 DOI: 10.1016/j.jep.2013.10.033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2013] [Revised: 09/24/2013] [Accepted: 10/17/2013] [Indexed: 06/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Hyangaa-Pyeongwi san is the most well known description in Traditional Chinese Medicine for treating functional gastrointestinal disorders. Functional dyspepsia (FD) is a main concern of intimidating quality of life (QoL) in recent days. Although many medicines have been developed to improve FD symptoms as well as QoL, there are no potential drugs and treatments for FD. The aim of this study is to investigate the effects of Hyangaa-Pyeongwi san (HPS) on QoL of patients with FD. METHODS This study was designed as a randomized, double blinded, placebo controlled, and parallel group trial. Participants received either placebo or HPS (9.68g of HPS at once, three times daily) for 4-weeks, and the efficacy evaluations were performed by assessing the Nepean Dyspepsia Index (NDI) and functional dyspepsia-quality of life (FD-QoL) at 0-, 4- and 8-weeks. RESULTS Total of 170 patients participated and were randomly allocated into placebo or HPS groups. Total symptom score of NDI decreased after 4-weeks trial in both groups (p>0.05). HPS significantly improved QoL scores, especially in the area of 'interference and eat/drink' in NDI (p=0.0031) as well as 'liveliness status', 'role-functioning status', and total score in FD-QoL (p=0.026 for liveliness status and p=0.035 for role-functioning status). This significant improvement of FD-QoL had lasted for 4-weeks. CONCLUSION HPS treatment is markedly effective in improving QoL in patients with FD. Moreover, we observed that this improvement had lasted for 4 weeks after finishing the trial through the follow-up study.
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Affiliation(s)
- Jeung-Bae Kim
- Internal Medicine of Immunology, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea
| | - Jang-Woo Shin
- Internal Medicine of Immunology, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea
| | - Ji-Young Kang
- Internal Medicine of Immunology, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea
| | - Chang-Gue Son
- Internal Medicine of Immunology, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea
| | - Weechang Kang
- Department of Business Information Statistics, College of Business Administration, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon 300-716, South Korea
| | - Hye-Won Lee
- TKM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, 461-24, Jeonmin-dong, Yuseong-gu, Daejeon, South Korea
| | - Dong-Soo Lee
- Department of Internal Medicine, Daejeon St. Mary's Hospital, The Catholic University of Korea, 520-2, Daehung-dong, Jung-gu, Daejeon, South Korea
| | - Yang-Chun Park
- Internal Medicine of Immunology and Lung, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea
| | - Jung-Hyo Cho
- Internal Medicine of Immunology, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, South Korea.
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Abstract
PURPOSE OF REVIEW Dyspepsia affects up to 40% of the general population and significantly reduces quality of life. A small proportion of patients have peptic ulcer disease as cause and this can be treated empirically with Helicobacter pylori eradication therapy in those that are infected. Approximately 20% have gastro-oesophageal reflux disease and this can be effectively treated with proton pump inhibitor therapy. Patients who remain symptomatic may warrant an endoscopy, but most will have functional dyspepsia. Treatment of functional dyspepsia remains a challenge. RECENT FINDINGS Recent large randomized trials suggest tricyclic antidepressant therapy may be effective in functional dyspepsia. A phase III randomized controlled trial reports that a new prokinetic, acotiamide, reduces dyspepsia symptoms in functional dyspepsia patients. There are also preliminary data that suggest buspirone, a drug that promotes gastric accommodation, is also effective in functional dyspepsia. There are also data to suggest that functional dyspepsia is caused by subtle manifestations of inflammation in the upper gastrointestinal tract, possibly caused by food sensitivity or a change in gut flora. SUMMARY The initial management of dyspepsia is well established, but managing those with continued symptoms is a challenge. Antidepressants and newer gastric motility agents show promise. Targeting the diet and gut microbiome is another area for future research in functional dyspepsia.
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Dai F, Lei Y, Li S, Song G, Chen JDZ. Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats. Am J Physiol Gastrointest Liver Physiol 2013; 305:G333-9. [PMID: 23764892 DOI: 10.1152/ajpgi.00224.2012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzyme-linked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 ± 2.3% (vs. saline 150.9 ± 2.7%, P < 0.001) and 128.2 ± 3.2% (vs. saline 171.1 ± 2.4%, P < 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P = 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P < 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.
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Affiliation(s)
- Fei Dai
- Ningbo Pace Translational Medical Research Center, Beilun, Ningbo, China.
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Moshiree B, Barboza J, Talley N. An update on current pharmacotherapy options for dyspepsia. Expert Opin Pharmacother 2013; 14:1737-53. [DOI: 10.1517/14656566.2013.809063] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Grover M, Camilleri M. Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. J Gastroenterol 2013; 48:177-81. [PMID: 23254779 PMCID: PMC3698430 DOI: 10.1007/s00535-012-0726-5] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 11/23/2012] [Indexed: 02/04/2023]
Abstract
The effects of antidepressants on the gastrointestinal tract may contribute to their potential efficacy in functional dyspepsia and irritable bowel syndrome; buspirone, a prototype 5-HT1A agonist, enhances gastric accommodation and reduces postprandial symptoms in response to a challenge meal. Paroxetine, a selective serotonin reuptake inhibitor, accelerates small bowel but not colonic transit, and this property may not be relevant to improve gut function in functional gastrointestinal disorders. Venlafaxine, a prototype serotonin norepinephrine reuptake inhibitor, enhances gastric accommodation, increases colonic compliance and reduces sensations to distension; however, it is associated with adverse effects that reduce its applicability in treatment of functional gastrointestinal disorders. Tricyclic antidepressants reduce sensations in response to food, including nausea, and delay gastric emptying, especially in females. Buspirone appears efficacious in functional dyspepsia; amitriptyline was not efficacious in a large trial of children with functional gastrointestinal disorders. Clinical trials of antidepressants for treatment of irritable bowel syndrome are generally small. The recommendations of efficacy and number needed to treat from meta-analyses are suspect, and more prospective trials are needed in patients without diagnosed psychiatric diseases. Antidepressants appear to be more effective in the treatment of patients with anxiety or depression, but larger prospective trials assessing both clinical and pharmacodynamic effects on gut sensorimotor function are needed.
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Affiliation(s)
- Madhusudan Grover
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, 200 First St. S.W, Charlton 8-110, Rochester, MN 55905 USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, 200 First St. S.W, Charlton 8-110, Rochester, MN 55905 USA
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Lackner JM, Keefer L, Jaccard J, Firth R, Brenner D, Bratten J, Dunlap LJ, Ma C, Byroads M. The Irritable Bowel Syndrome Outcome Study (IBSOS): rationale and design of a randomized, placebo-controlled trial with 12 month follow up of self- versus clinician-administered CBT for moderate to severe irritable bowel syndrome. Contemp Clin Trials 2012; 33:1293-310. [PMID: 22846389 PMCID: PMC3468694 DOI: 10.1016/j.cct.2012.07.013] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 07/21/2012] [Accepted: 07/23/2012] [Indexed: 12/16/2022]
Abstract
Irritable bowel syndrome is a common, oftentimes disabling, gastrointestinal disorder whose full range of symptoms has no satisfactory medical or dietary treatment. One of the few empirically validated treatments includes a specific psychological therapy called cognitive behavior therapy which, if available, is typically administered over several months by trained practitioners in tertiary care settings. There is an urgent need to develop more efficient versions of CBT that require minimal professional assistance but retain the efficacy profile of clinic based CBT. The Irritable Bowel Syndrome Outcome Study (IBSOS) is a multicenter, placebo-controlled randomized trial to evaluate whether a self-administered version of CBT is, at least as efficacious as standard CBT and more efficacious than an attention control in reducing core GI symptoms of IBS and its burden (e.g. distress, quality of life impairment, etc.) in moderately to severely affected IBS patients. Additional goals are to assess, at quarterly intervals, the durability of treatment response over a 12 month period; to identify clinically useful patient characteristics associated with outcome as a way of gaining an understanding of subgroups of participants for whom CBT is most beneficial; to identify theory-based change mechanisms (active ingredients) that explain how and why CBT works; and evaluate the economic costs and benefits of CBT. Between August 2010 when IBSOS began recruiting subjects and February 2012, the IBSOS randomized 171 of 480 patients. Findings have the potential to improve the health of IBS patients, reduce its social and economic costs, conserve scarce health care resources, and inform evidence-based practice guidelines.
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Affiliation(s)
- Jeffrey M Lackner
- Department of Medicine, University at Buffalo School of Medicine, SUNY, Buffalo, NY, USA.
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Lacy BE, Talley NJ, Locke GR, Bouras EP, DiBaise JK, El-Serag HB, Abraham BP, Howden CW, Moayyedi P, Prather C. Review article: current treatment options and management of functional dyspepsia. Aliment Pharmacol Ther 2012; 36:3-15. [PMID: 22591037 PMCID: PMC3970847 DOI: 10.1111/j.1365-2036.2012.05128.x] [Citation(s) in RCA: 159] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Revised: 02/26/2012] [Accepted: 04/21/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and early satiety (50-82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. AIM To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). RESULTS The utility of Helicobacter pylori eradication for the treatment of FD is modest (6-14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35% therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA) (response rates of 64-70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. CONCLUSIONS A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.
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Affiliation(s)
- B E Lacy
- Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
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Herrick LM, Locke GR, Zinsmeister AR, Talley NJ. Challenges and lessons learned in conducting comparative-effectiveness trials. Am J Gastroenterol 2012; 107:644-9. [PMID: 22552235 PMCID: PMC3935288 DOI: 10.1038/ajg.2011.475] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.
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Affiliation(s)
- Linda M. Herrick
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
,School of Nursing, University of Minnesota, Rochester, Minnesota, USA
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Nicholas J. Talley
- Department of Medicine, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia
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