|
1
|
Gómez-Escudero O, Remes-Troche JM, Coss-Adame E, García-Zermeño KR, Aquino-Matus J, Jiménez-Pavón J, Valdovinos-García LR, Vargas-Martínez MA, Amieva-Balmori M, Arenas-Martínez JS, Félix-Téllez FA, Gómez-Castaños PC, Mejía-Rivas M, Valdovinos-Díaz MA, Vázquez-Elizondo G, Villar-Chávez AS, Gyawali CP. Clinical practice recommendations on the use of neuromodulators in gastroenterology: AMG (Asociación Mexicana de Gastroenterología) - AMNM (Asociación Mexicana de Neurogastroenterología y Motilidad) expert joint review. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025:S2255-534X(25)00007-6. [PMID: 40374462 DOI: 10.1016/j.rgmxen.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 12/20/2024] [Indexed: 05/17/2025]
Abstract
Disorders of gut-brain interaction (DGBI) are characterized by alterations in both central and peripheral gut-brain axis (GBA)-related stimuli, and include esophageal, gastroduodenal, intestinal and anorectal disorders. Despite the fact that several pathophysiologic mechanisms are involved, the mainstay of treatment is neuromodulators, a heterogeneous group of drugs that act on pathways related to central and peripheral pain processing. This expert review by both the AMG (Asociación Mexicana de Gastroenterología) and AMNM (Asociación Mexicana de Neurogastroenterología y Motilidad) summarizes a series of updated clinical recommendations based on an exhaustive review of the literature, regarding the use of neuromodulators for DGBI, and is grouped into six sections: pharmacologic principles, definition, classification, mechanism of action, indications and use in each DGBI subtype, up/downscaling strategies, combination therapy, adverse events, joint use along with psychiatry in the case of comorbidities, and non-pharmacologic neuromodulation. Furthermore, drug selection process tips and dose personalization according to individual groups and sensitivities are provided, and special cases with DGBI-psychiatric comorbidity, as well as overlap with another DGBI, are considered.
Collapse
Affiliation(s)
- O Gómez-Escudero
- Clínica de Gastroenterología, Endoscopia, Neurogastroenterología y Motilidad Gastrointestinal "Endoneurogastro", Hospital Ángeles Puebla, Puebla, Puebla, Mexico
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico.
| | - E Coss-Adame
- Departamento de Gastroenterología, Laboratorio de Motilidad Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - K R García-Zermeño
- Centro Integral de Gastroenterología y Motilidad Avanzada (CIGMA), Boca del Río, Veracruz, Mexico
| | - J Aquino-Matus
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - J Jiménez-Pavón
- Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz - Clínica de Trastornos Afectivos, Hospital Médica Sur, Mexico City, Mexico
| | - L R Valdovinos-García
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico; Servicio de Gastroenterología, Hospital Médica Sur, Mexico City, Mexico
| | - M A Vargas-Martínez
- Departamento de Neurología y Psiquiatría, Servicio de Psiquiatría de Enlace, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - J S Arenas-Martínez
- Posgrado de Alta Especialidad en Medicina (Neurogastroenterología), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - F A Félix-Téllez
- Posgrado de Alta Especialidad en Medicina (Neurogastroenterología), Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - P C Gómez-Castaños
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | | | | | - G Vázquez-Elizondo
- Centro de Enfermedades Digestivas ONCARE/Gastro Alliance Center, Monterrey, Nuevo León, Mexico
| | | | - C P Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, MO, United States
| |
Collapse
|
|
2
|
Greenwood BM, Garfinkel SN. Interoceptive Mechanisms and Emotional Processing. Annu Rev Psychol 2025; 76:59-86. [PMID: 39423429 DOI: 10.1146/annurev-psych-020924-125202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2024]
Abstract
Interoception, the sensing of internal bodily signals, is intricately linked with the experience of emotions. Various theoretical models of emotion incorporate aspects of interoception as a fundamental component alongside higher-order processes such as the appraisal of internal signals guided by external context. Interoception can be delineated into different dimensions, which include the nature of afferent signals, the accuracy with which they can be sensed, their neural processing, and the higher-order interpretation of these signals. This review methodically evaluates these interoceptive dimensions through empirical research to illustrate their role in shaping emotions. Clinical and neurodevelopmental conditions characterized by altered emotional profiles, such as anxiety, depression, schizophrenia, posttraumatic stress disorder, emotionally unstable personality disorder, and autism, exhibit distinct changes in interoception. Various therapeutic approaches, including behavioral, pharmacological, and psychological strategies, may be efficacious for treating conditions associated with emotional alterations by targeting interoceptive mechanisms.
Collapse
Affiliation(s)
- Benedict M Greenwood
- Institute of Cognitive Neuroscience, University College London, London, United Kingdom;
| | - Sarah N Garfinkel
- Institute of Cognitive Neuroscience, University College London, London, United Kingdom;
| |
Collapse
|
|
3
|
Yeh JH, Chen CL, Sifrim D, Fass R, Wang WL, Hsu CC, Lei WY. Central neuromodulators for patients with functional esophageal disorders: A systematic review and meta-analysis. Dig Liver Dis 2024; 56:1675-1682. [PMID: 38851975 DOI: 10.1016/j.dld.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 06/10/2024]
Abstract
BACKGROUD The use of neuromodulators is prevalent in various functional gastrointestinal disease. However, data concerning the outcomes of these treatments in functional esophageal disorders (FED) remains limited and inadequate. AIMS The aim of the present study is to examine the efficacy of central neuromodulators in FED. METHODS We searched PubMed, EMBASE, and the Cochrane library databases from inception to April 2023. Randomized controlled trials that compared the effects of neuromodulators and placebos on FED are included. Primary outcome is the symptom improvement, and Rome IV criteria is used to assess eligible studies. RESULTS Eleven randomized controlled studies (three for functional chest pain, four for reflux hypersensitivity/functional heartburn, three for globus, and one for functional dysphagia) were included in the final analysis. Neuromodulators reduced chest pain by 52%-71% in patients with functional chest pain, and alleviated symptom by 46%-75% in patients with globus (n = 3, Odds ratio 6.30, 95% confidence interval 4.17-9.50). However, the results were inconsistent for reflux hypersensitivity and functional heartburn. There was a lack of convincing evidence to support the use of neuromodulators for functional dysphagia. The use of neuromodulators did not have a significant impact on the quality of life. CONCLUSIONS Functional chest pain and globus may potentially benefit from the use of neuromodulators, but their effectiveness for functional dysphagia, functional heartburn and reflux hypersensitivity remains controversial. More controlled trials are needed to confirm the therapeutic effects on these conditions.
Collapse
Affiliation(s)
- Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA DaChang Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Medical technology, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Ronnie Fass
- The Esophageal and Swallowing Center, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH, USA
| | - Wen-Lun Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chia Chang Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.
| |
Collapse
|
|
4
|
Livermore JJA, Skora LI, Adamatzky K, Garfinkel SN, Critchley HD, Campbell-Meiklejohn D. General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation. Transl Psychiatry 2024; 14:241. [PMID: 38844469 PMCID: PMC11156930 DOI: 10.1038/s41398-024-02971-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 05/22/2024] [Accepted: 05/29/2024] [Indexed: 06/09/2024] Open
Abstract
Ordinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg CITALOPRAM) and a PLACEBO. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of CITALOPRAM on sensory processing. CITALOPRAM was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, CITALOPRAM reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region's response to attended heart sensation observed with PLACEBO. Preliminary post hoc analysis indicated that CITALOPRAM effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.
Collapse
Affiliation(s)
| | - Lina I Skora
- School of Psychology, University of Sussex, Brighton, UK
- Heinrich Heine Universität, Düsseldorf, Germany
- Sussex Centre for Consciousness Science, University of Sussex, Brighton, UK
| | | | - Sarah N Garfinkel
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Hugo D Critchley
- Sussex Centre for Consciousness Science, University of Sussex, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
- Sussex Partnership NHS Foundation Trust, Brighton, UK
| | | |
Collapse
|
|
5
|
Kasugai K, Ogasawara N. Gastroesophageal Reflux Disease: Pathophysiology and New Treatment Trends. Intern Med 2024; 63:1-10. [PMID: 36927966 PMCID: PMC10824640 DOI: 10.2169/internalmedicine.1551-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 02/02/2023] [Indexed: 03/15/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is caused by the reflux of gastric contents into the esophagus due to a decline in esophageal clearance and anti-reflux barrier mechanisms. Mucosal injury is caused by a combination of gastric juice directly damaging the esophageal mucosa and the immune and inflammatory mechanism in which inflammatory cytokines released from the esophageal mucosal epithelium cause neutrophil migration, triggering inflammation. Gastric secretion inhibitors are the first-line treatment for GERD, but they can be combined with prokinetic agents and Chinese herbal remedies. However, pharmacotherapy cannot improve anatomical problems or prevent physical causes of GERD, such as reflux of non-acidic contents. Therefore, surgery can be warranted, depending on the pathology. Intraluminal endoscopic therapy, which is both less invasive and more effective than surgery, was recently developed and applied in Europe and the United States. In Japan, intraluminal endoscopic therapies, such as anti-reflux mucosectomy, anti-reflux mucosal ablation, and endoscopic submucosal dissection, for GERD have been independently developed.
Collapse
Affiliation(s)
- Kunio Kasugai
- Department of Internal Medicine, Division of Gastroenterology, Aichi Medical University, Japan
| | - Naotaka Ogasawara
- Department of Internal Medicine, Division of Gastroenterology, Aichi Medical University, Japan
| |
Collapse
|
|
6
|
Ribolsi M, Marchetti L, Blasi V, Cicala M. Anxiety correlates with excessive air swallowing and PPI refractoriness in patients with concomitant symptoms of GERD and functional dyspepsia. Neurogastroenterol Motil 2023; 35:e14550. [PMID: 36786093 DOI: 10.1111/nmo.14550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/18/2023] [Accepted: 02/01/2023] [Indexed: 02/15/2023]
Abstract
BACKGROUND Anxiety may exacerbate GERD and FD symptoms perception and reduce quality of life. As many as 50% of patients with GERD symptoms have incomplete relief with PPI therapy, and psychological factors may influence PPI responsiveness. AIM The potential relationship between anxiety, excessive air swallowing, and PPI responsiveness was evaluated. METHODS GERD patients with concomitant FD were prospectively evaluated. Validated structured questionnaires were used to evaluate anxiety, GERD, and FD symptoms. All patients were treated, within the previous year, with at least 8 weeks of standard dose PPI therapy. RESULTS One hundred sixty-one patients were included. Frequency of non-responders in patients with moderate/severe anxiety was significantly higher compared to patients with mild anxiety (62.7% vs. 37.3%, p < 0.01). Patients with moderate/severe anxiety displayed a significantly higher mean FD symptoms score value compared to patients with mild anxiety. A significantly higher mean number of air swallows were observed in patients with moderate/severe anxiety. At ROC analysis, air swallows and mixed reflux episodes were significantly associated with the presence of PPI refractoriness (AUC: 0.725, 95% CI: 0.645-0.805 and 0.768, 0.692-0.843). According to univariate analysis, an abnormal number of air swallows, mixed reflux episodes and presence of moderate/severe anxiety was significantly associated with PPI refractoriness. CONCLUSION Our results, if confirmed in in a larger, prospective clinical and therapeutic study, demonstrate the usefulness of an up-front evaluation with anxiety questionnaire and esophageal testing in patients with a broad spectrum of upper gastrointestinal symptoms who fail to respond to PPI treatment, supporting the option of alternative treatment modalities.
Collapse
Affiliation(s)
- Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Lorenzo Marchetti
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Valentina Blasi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Michele Cicala
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| |
Collapse
|
|
7
|
Alkhowaiter SS, Alshahrani AH, Almarzouqi HF, Alonazi GK, Alhawassi TM, AlRasheed MM. Feasibility, and barriers to use escitalopram in functional gastrointestinal disorders. Front Pharmacol 2023; 14:1131354. [PMID: 37284319 PMCID: PMC10240913 DOI: 10.3389/fphar.2023.1131354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/28/2023] [Indexed: 06/08/2023] Open
Abstract
Background and study aims: The feasibility and barriars of escitalopram use in patients with functional gastrointestinal disorders (FGIDs) are still debated. We aimed to evaluate the feasibility, safety and efficacy and barriars of escitalopram use in managing FGIDs in the Saudi population. Patients and Methods: We included 51 patients who received escitalopram for irritable bowel syndrome (n = 26), functional heartburn (n = 10), globus sensation (n = 10) or combined disorders (n = 5). We used an irritable bowel syndrome-severity scoring system IBS-SSS), GerdQ questionnaire and Glasgow Edinburg Throat Scale (GETS) to assess disease severity change before and after treatment. Results: The median age was 33 years (25th- 75th percentiles: 29-47), and 26 (50.98%) were males. Forty-one patients experienced side effects (80.39%), but most side effects were mild. The most common side effects were drowsiness/fatigue/dizziness (54.9%), xerostomia (23.53%), nausea/vomiting (21.57%) and weight gain (17.65%). IBS-SSS was 375 (255-430) and 90 (58-205) before and after treatment, respectively (p < 0.001). GerdQ score was 12 (10-13) before treatment and 7 (6-10) after treatment (p = 0.001). GETS score before treatment was 32.5 (21-46) and after treatment became 22 (13-31) (p = 0.002). Thirty-five patients refused to take the medications, and seven patients discontinued the medication. Possible causes of the poor compliance were fear of the medications and not being convinced of taking psychiatric medications for functional disorders (n = 15). Conclusion: Escitalopram could be a safe and effective treatment for functional gastrointestinal disorders. Targeting and managing factors leading to poor compliance could further improve the treatment outcome.
Collapse
Affiliation(s)
- Saad S. Alkhowaiter
- Department of Medicine- Gastroenterology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Amani H. Alshahrani
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Hala F. Almarzouqi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Gadah K. Alonazi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Tariq M. Alhawassi
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Maha M. AlRasheed
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
|
8
|
Wong MW, Liu TT, Yi CH, Lei WY, Hung JS, Cock C, Omari T, Gyawali CP, Liang SW, Lin L, Chen CL. Oesophageal hypervigilance and visceral anxiety relate to reflux symptom severity and psychological distress but not to acid reflux parameters. Aliment Pharmacol Ther 2021; 54:923-930. [PMID: 34383968 DOI: 10.1111/apt.16561] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 06/21/2021] [Accepted: 07/21/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity. AIMS To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD. METHODS Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded. RESULTS We enrolled 105 patients, aged 21-64 years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05). CONCLUSIONS EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
Collapse
Affiliation(s)
- Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.,School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
| | - Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Charles Cock
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Taher Omari
- Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Chandra Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Lin Lin
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| |
Collapse
|
|
9
|
Oldfield EC, Parekh PJ, Johnson DA. Diagnosis and Treatment of Esophageal Chest Pain. THE ESOPHAGUS 2021:18-37. [DOI: 10.1002/9781119599692.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
10
|
Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol 2021; 19:1314-1326. [PMID: 32246998 DOI: 10.1016/j.cgh.2020.03.057] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/23/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.
Collapse
Affiliation(s)
- Dhyanesh Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth System, Case Western Reserve University, Cleveland, Ohio
| | - Michael Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| |
Collapse
|
|
11
|
Broers C, Geeraerts A, Boecxstaens V, Van Houtte B, Geysen H, Peersman N, Vermeersch P, Vanuytsel T, Tack J, Pauwels A. The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health. Neurogastroenterol Motil 2021; 33:e14057. [PMID: 33280212 DOI: 10.1111/nmo.14057] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 10/22/2020] [Accepted: 11/17/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). METHODS Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40 mg; 5-HT reuptake inhibitor; intravenous) was investigated (n = 14). In the second study, the effect of buspirone (20 mg; 5HT1A agonist; oral) was investigated (n = 10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n = 15). KEY RESULTS No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p > 0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p = 0.017, Cohen's d+ = 0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. CONCLUSIONS AND INFERENCES ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.
Collapse
Affiliation(s)
- Charlotte Broers
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Annelies Geeraerts
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Veerle Boecxstaens
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Brecht Van Houtte
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Hannelore Geysen
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Nele Peersman
- Clinical Department of Laboratory Medicine, University Hospital Leuven, Leuven, Belgium
| | - Pieter Vermeersch
- Clinical Department of Laboratory Medicine, University Hospital Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Ans Pauwels
- Translational Research Centre for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| |
Collapse
|
|
12
|
Abstract
Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett's esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of Helicobacter pylori. Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
Collapse
Affiliation(s)
- David A Katzka
- Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, MN, USA
| | - Peter J Kahrilas
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL USA
| |
Collapse
|
|
13
|
Sharma P, Yadlapati R. Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid. Ann N Y Acad Sci 2020; 1486:3-14. [PMID: 33015827 DOI: 10.1111/nyas.14501] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/24/2020] [Accepted: 09/01/2020] [Indexed: 12/14/2022]
Abstract
Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD.
Collapse
Affiliation(s)
- Priya Sharma
- Department of Medicine, University of California San Diego School of Medicine, La Jolla, California
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego School of Medicine, Center for Esophageal Diseases, La Jolla, California
| |
Collapse
|
|
14
|
Manolakis AC, Broers C, Geysen H, Goelen N, Van Houtte B, Rommel N, Vanuytsel T, Tack J, Pauwels A. Effect of citalopram on esophageal motility in healthy subjects-Implications for reflux episodes, dysphagia, and globus. Neurogastroenterol Motil 2019; 31:e13632. [PMID: 31121087 DOI: 10.1111/nmo.13632] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 05/07/2019] [Accepted: 05/07/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano-chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. METHODS Sixteen healthy volunteers (HV) receiving 20 mg citalopram or placebo intravenously, in a randomized cross-over fashion, underwent two high-resolution impedance manometry studies involving liquid swallows and a high-fat, high-caloric meal. Manometric, reflux, and symptom-related parameters were studied. KEY RESULTS A lower distal contractile integral was recorded under citalopram, compared with placebo (P = 0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P < 0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P < 0.0001, in both cases) and this was also the case for the 0.2 s integrated relaxation pressure (P = 0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P < 0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P = 0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P = 0.06). This citalopram-induced globus was associated with higher UES postswallow mean and maximum pressure values (P = 0.01 and P = 0.04, respectively). CONCLUSIONS AND INFERENCES Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug-induced globus.
Collapse
Affiliation(s)
- Anastassios C Manolakis
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.,Department of Gastroenterology, University Hospital of Larissa, Larissa, Greece
| | - Charlotte Broers
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Hannelore Geysen
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Nick Goelen
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Brecht Van Houtte
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Nathalie Rommel
- Experimental Oto-Rhino-Laryngology, Department of Neurosciences, Deglutology, KU Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ans Pauwels
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| |
Collapse
|
|
15
|
Hungin APS, Molloy-Bland M, Scarpignato C. Revisiting Montreal: New Insights into Symptoms and Their Causes, and Implications for the Future of GERD. Am J Gastroenterol 2019; 114:414-421. [PMID: 30323266 PMCID: PMC6434899 DOI: 10.1038/s41395-018-0287-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 08/13/2018] [Indexed: 12/11/2022]
Abstract
The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.
Collapse
Affiliation(s)
- A. Pali S. Hungin
- The Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | | | - Carmelo Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Parma, Italy
| |
Collapse
|
|
16
|
Ford AC, Lacy BE, Harris LA, Quigley EMM, Moayyedi P. Effect of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-Analysis. Am J Gastroenterol 2019; 114:21-39. [PMID: 30177784 DOI: 10.1038/s41395-018-0222-5] [Citation(s) in RCA: 249] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. METHODS We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or "usual management" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or "usual management", and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57-0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter (I(2) = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62-0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies (I(2) = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding. CONCLUSIONS Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result.
Collapse
Affiliation(s)
- Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - Brian E Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Lucinda A Harris
- Division of Gastroenterology and Hepatology, Mayo School of Medicine, Scottsdale, AZ, USA
| | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA
| | - Paul Moayyedi
- Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, ON, Canada
| |
Collapse
|
|
17
|
Chi ZC. Reflux hypersensitivity. Shijie Huaren Xiaohua Zazhi 2018; 26:885-891. [DOI: 10.11569/wcjd.v26.i15.885] [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: 02/06/2023] Open
Abstract
Reflux hypersensitivity (RH) is a condition characterized typically by heart burn, normal gastroscopy and esophageal biopsy, normal esophageal pH-impedance test, and a close correlation between heart burn and reflux events. Recently, Rome Ⅳ criteria suggests that reflux hypersensitivity is a new type of esophageal functional disease. It is very common in clinical practice and often coexists with functional heartburn. Diagnosis is based on heartburn symptoms, gastroscopy, esophageal biopsy, esophageal pH-impedance, and high resolution esophageal pressure. RH patients have normal acid exposure, and there is no dynamic disease in esophageal dynamic test. However, there are still some difficulties in the differential diagnosis of esophageal functional diseases. Symptom associated probability cannot reliably distinguish reflux hypersensitivity and functional heartburn. The pathogenesis of RH is not entirely clear. Recent studies have shown that esophageal sensitivity to acid and mucosal integrity can lead to RH. Because more than 90% of patients do not respond to proton pump inhibitors, esophageal neuromodulators, such as tricyclic antidepressants, are the main treatment, but the efficacy is uncertain. Surgery is a desirable method, but the indications should be strictly selected. In the future, it is important to strengthen the research of RH pathogenesis and seek new therapeutic targets.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
18
|
Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology 2018; 154:1140-1171.e1. [PMID: 29274869 DOI: 10.1053/j.gastro.2017.11.279] [Citation(s) in RCA: 265] [Impact Index Per Article: 37.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Revised: 11/13/2017] [Accepted: 11/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Central neuromodulators (antidepressants, antipsychotics, and other central nervous system-targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut-brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations. METHODS The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee. RESULTS The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6-12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient-provider relationship. CONCLUSIONS Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.
Collapse
Affiliation(s)
- Douglas A Drossman
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina; Center for Education and Practice of Biopsychosocial Care and Drossman Gastroenterology, Chapel Hill, North Carolina.
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Alexander C Ford
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom
| | - Eva Szigethy
- Departments of Psychiatry and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Hans Törnblom
- Departments of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lukas Van Oudenhove
- Laboratory for Brain-Gut Axis Studies, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| |
Collapse
|
|
19
|
Ban MJ, Kim WS, Park KN, Kim JW, Lee SW, Han K, Chang JW, Byeon HK, Koh YW, Park JH. Korean survey data reveals an association of chronic laryngitis with tinnitus in men. PLoS One 2018; 13:e0191148. [PMID: 29324903 PMCID: PMC5764343 DOI: 10.1371/journal.pone.0191148] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 01/02/2018] [Indexed: 12/12/2022] Open
Abstract
The association between chronic laryngitis and tinnitus is not a well-studied topic, unlike the association of these two conditions with many other disorders. Cross-sectional data of 11,347 adults (males: 4,934; females: 6,413), who completed the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012 were used to investigate this association. Lifestyle patterns, including smoking and alcohol habits, regular exercise, physical and mental health status, socioeconomic status, nutritional status, and other chronic diseases, were analyzed. Chronic laryngitis and tinnitus were diagnosed by field survey teams, which included otolaryngologists, who conducted chronic disease surveillance using a health status interview, a nutritional status questionnaire, and a physical examination. Chronic laryngitis was significantly associated with age, education beyond high school, depressed mood, voice change, metabolic syndrome, and tinnitus in men. In women, chronic laryngitis was associated with body mass index and diabetes mellitus. Chronic laryngitis in men was significantly associated with tinnitus (odds ratio 1.671, [95% confidence interval: 1.167-2.393]) after adjusting for age, body mass index, smoking status, alcohol intake, regular exercise, metabolic syndrome, education beyond high school, and depressed mood. Additionally, the prevalence of chronic laryngitis increased with increasing severity of tinnitus in men alone (P = 0.002). The study revealed a significant association between chronic laryngitis and tinnitus.
Collapse
Affiliation(s)
- Myung Jin Ban
- Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea.,Department of Medicine, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - Won Shik Kim
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
| | - Ki Nam Park
- Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Jae Wook Kim
- Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Seung Won Lee
- Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae Won Chang
- Department of Otorhinolaryngology, Chungnam National University College of Medicine, Daejeon, Korea
| | - Hyung Kwon Byeon
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Woo Koh
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hong Park
- Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| |
Collapse
|
|
20
|
Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology 2018; 154:302-318. [PMID: 28827081 DOI: 10.1053/j.gastro.2017.07.049] [Citation(s) in RCA: 198] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 07/29/2017] [Accepted: 07/31/2017] [Indexed: 02/06/2023]
Abstract
Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.
Collapse
Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio.
| |
Collapse
|
|
21
|
Kung YM, Hsu WH, Wu MC, Wang JW, Liu CJ, Su YC, Kuo CH, Kuo FC, Wu DC, Wang YK. Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease. Dig Dis Sci 2017; 62:3298-3316. [PMID: 29110162 DOI: 10.1007/s10620-017-4830-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 10/25/2017] [Indexed: 12/15/2022]
Abstract
The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.
Collapse
Affiliation(s)
- Yu-Min Kung
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 100 Tz-You 1st road, Kaohsiung, 807, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Chieh Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Chung-Jung Liu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Chung Su
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fu-Chen Kuo
- School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. .,Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 100 Tz-You 1st road, Kaohsiung, 807, Taiwan.
| |
Collapse
|
|
22
|
Yamasaki T, Fass R. Reflux Hypersensitivity: A New Functional Esophageal Disorder. J Neurogastroenterol Motil 2017; 23:495-503. [PMID: 28992673 PMCID: PMC5628981 DOI: 10.5056/jnm17097] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 09/08/2017] [Indexed: 12/13/2022] Open
Abstract
Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients’ heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.
Collapse
Affiliation(s)
- Takahisa Yamasaki
- Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH, USA
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH, USA
| |
Collapse
|
|
23
|
Abstract
Patients with functional GI disorders (FGIDs) are commonplace in the gastroenterologist's practice. A number of these patients may be refractory to peripherally acting agents, yet respond to central neuromodulators. There are benefits and potential adverse effects to using TCAs, SSRIs, SNRIs, atypical antipsychotics, and miscellaneous central neuromodulators in these patients. These agents can benefit mood, pain, diarrhea, constipation, nausea, sleep, and depression. The mechanisms by which they work, the differences between classes and individual agents, and the various adverse effects are outlined. Dosing, augmentation strategies, and treatment scenarios specifically for painful FGIDs, FD with PDS, and chronic nausea and vomiting syndrome are outlined.
Collapse
|
|
24
|
Abstract
Swallowing involves complex coordination of the neuromuscular anatomy and physiology of the oropharynx and esophagus, controlled by the enteric and central nervous systems. Dysphagia is classified as either oropharyngeal or esophageal and results from mechanical or structural disturbances. Videofluoroscopy, fiberoptic endoscopic evaluation of swallowing, barium swallow, manometry, and endoscopy are common modalities utilized in diagnosis, but none is as important as a patient's history. Functional dysphagia is a diagnosis of exclusion and is based on Rome criteria. Its mechanism is unknown but potentially related to visceral hypersensitivity, inappropriate pain perception, or unidentified contraction abnormalities. Its management is mainly supportive; however, there is literature to suggest, but not confirm, benefit with the use of antidepressants. Continued understanding of functional dysphagia and other functional esophageal disorders, including globus sensation, will require further investigation into diagnostic algorithms and finding treatment methods.
Collapse
Affiliation(s)
- A Baumann
- Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - P O Katz
- Division of Gastroenterology, Albert Einstein Medical Center, Philadelphia, PA, USA.
| |
Collapse
|
|
25
|
Malik Z, Bayman L, Valestin J, Rizvi-Toner A, Hashmi S, Schey R. Dronabinol increases pain threshold in patients with functional chest pain: a pilot double-blind placebo-controlled trial. Dis Esophagus 2017; 30:1-8. [PMID: 26822791 DOI: 10.1111/dote.12455] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings.
Collapse
Affiliation(s)
- Z Malik
- Section of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania, USA
| | - L Bayman
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - J Valestin
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - A Rizvi-Toner
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - S Hashmi
- Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| | - R Schey
- Section of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania, USA.,Division of Gastroenterology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
| |
Collapse
|
|
26
|
Hoff DAL, Brock C, Farmer AD, Dickman R, Ruffle JK, Shaker A, Drewes AM. Pharmacological and other treatment modalities for esophageal pain. Ann N Y Acad Sci 2016; 1380:58-66. [PMID: 27442914 DOI: 10.1111/nyas.13151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 05/23/2016] [Accepted: 05/25/2016] [Indexed: 12/11/2022]
Abstract
Treatment of esophageal pain remains a major challenge for the clinician. Although many patients have heartburn and may respond to proton pump inhibitors, there in an unmet need for other treatment modalities in patients where there are no obvious pathological findings. Although analgesics are the mainstay in esophageal pain treatment, many patients are nonresponders to these drugs. The current concise review focuses on other systems affecting pain processing, where better understanding may serve as a framework for therapy. These are the parasympathetic nervous system, exercise, and personality profiles. Finally, treatment with analgesics for functional chest pain remains a challenge, and an overview of treatment with antidepressive drugs is provided.
Collapse
Affiliation(s)
- Dag Arne Lihaug Hoff
- Clinic of Medicine HMR Hospital Trust, Department of Medicine, Division of Gastroenterology & Hepatology, Aalesund Hospital, Aalesund, Norway.
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark
| | - Adam D Farmer
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark
- Centre for Digestive Diseases, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom
- Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, United Kingdom
| | - Ram Dickman
- Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petach Tikva & Sackler School of Medicine, University of Tel Aviv, Israel
| | - James K Ruffle
- Centre for Digestive Diseases, Blizard Institute, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom
| | - Anisa Shaker
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California, Keck School of Medicine, Los Angeles, California
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark
| |
Collapse
|
|
27
|
Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol 2016; 13:281-94. [PMID: 27075264 DOI: 10.1038/nrgastro.2016.50] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The management of patients with refractory GERD (rGERD) is a major clinical challenge for gastroenterologists. In up to 30% of patients with typical GERD symptoms (heartburn and/or regurgitation), acid-suppressive therapy does not provide clinical benefit. In this Review, we discuss the current management algorithm for GERD and the features and management of patients who do not respond to treatment (such as those individuals with an incorrect diagnosis of GERD, inadequate PPI intake, persisting acid reflux and persisting weakly acidic reflux). Symptom response to existing surgical techniques, novel antireflux procedures, and the value of add-on medical therapies (including prokinetics and reflux inhibitors) for rGERD symptoms are discussed. Pharmaceutical agents targeting oesophageal sensitivity, a condition that can contribute to symptom generation in rGERD, are also discussed. Finally, on the basis of available published data and our expert opinion, we present an outline of a current, usable algorithm for management of patients with rGERD that considers the timing and diagnostic use of pH-impedance monitoring on or off PPI, additional diagnostic tests, the clinical use of baclofen and the use of add-on neuromodulators (tricyclic agents and selective serotonin reuptake inhibitors).
Collapse
Affiliation(s)
- Emidio Scarpellini
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.,Division Gastroenterology, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Daphne Ang
- Division of Gastroenterology, Changi General Hospital, 2 Simei Street 3, Singapore 529889
| | - Ans Pauwels
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
| | - Adriano De Santis
- Division of Gastroenterology, Changi General Hospital, 2 Simei Street 3, Singapore 529889
| | - Tim Vanuytsel
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
| | - Jan Tack
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
| |
Collapse
|
|
28
|
|
|
29
|
Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial. Am J Gastroenterol 2016; 111:217-24. [PMID: 26753892 DOI: 10.1038/ajg.2015.413] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Accepted: 11/10/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. METHODS Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. RESULTS Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). CONCLUSIONS Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.
Collapse
|
|
30
|
Established and Emerging Treatment Options for Functional Heartburn and Chest Pain. ACTA ACUST UNITED AC 2016; 14:19-27. [DOI: 10.1007/s11938-016-0081-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
31
|
Ruiz de León San Juan A, Ciriza de los Ríos C, Pérez de la Serna Bueno J, Canga Rodríguez-Valcárcel F, Estremera Arévalo F, García Sánchez R, Huamán Ríos JW, Pérez Fernández MT, Santander Vaquero C, Serra Pueyo J, Sevilla Mantilla C, Barba Orozco E, Bosque López MJ, Casabona Francés S, Carrión Bolorino S, Castillo Grau P, Delgado Aros S, Domínguez Carbajo AB, Fernández Orcajo P, García-Lledó J, Gigantó Tomé F, Iglesias Picazo R, Lacima Vidal G, López López P, Llabrés Rosselló M, Mas Mercader P, Mego Silva M, Mendarte Barrenetxea MU, Miliani Molina C, Oreja Arrayago M, Sánchez Ceballos F, Sánchez Prudencio S. Practical aspects of high resolution esophageal manometry. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2016; 109:91-105. [DOI: 10.17235/reed.2016.4441/2016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
32
|
Boeckxstaens G, El-Serag HB, Smout AJPM, Kahrilas PJ. Republished: symptomatic reflux disease: the present, the past and the future. Postgrad Med J 2015; 91:46-54. [PMID: 25583739 PMCID: PMC4316838 DOI: 10.1136/postgradmedj-2013-306393rep] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.
Collapse
Affiliation(s)
- Guy Boeckxstaens
- Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| |
Collapse
|
|
33
|
Ravi K, Katzka DA. Diagnosis and medical management of esophageal dysmotility. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2015. [DOI: 10.1016/j.tgie.2015.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
|
|
34
|
Weijenborg PW, de Schepper HS, Smout AJPM, Bredenoord AJ. Effects of antidepressants in patients with functional esophageal disorders or gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol 2015; 13:251-259.e1. [PMID: 24997325 DOI: 10.1016/j.cgh.2014.06.025] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 06/01/2014] [Accepted: 06/18/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with functional esophageal disorders present with symptoms of chest pain, heartburn, dysphagia, or globus in the absence of any structural abnormality. Visceral hypersensitivity is a feature of these functional disorders, and might be modulated by antidepressant therapy. We evaluated evidence for the efficacy of antidepressant therapy for symptoms associated with esophageal visceral hypersensitivity in patients with functional esophageal disorders or gastroesophageal reflux disease (GERD). METHODS We performed a systematic search of the Cochrane Comprehensive Trial Register, MEDLINE, and EMBASE (through February 2014). We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy on experimentally induced esophageal sensation or intensity, or frequency of heartburn, chest pain, dysphagia, or globus. RESULTS The search strategy identified 378 articles; 15 described randomized controlled trials that were eligible for inclusion. In addition, 1 conference abstract and 2 case reports were included, providing the best available evidence on specific symptoms. Esophageal pain thresholds increased by 7% to 37% after antidepressant therapy. Antidepressant therapy reduced functional chest pain over a range from 18% to 67% and reduced heartburn in patients with GERD over a range of 23% to 61%. One study included patients with globus and none of the studies included patients with functional heartburn or functional dysphagia. CONCLUSIONS Based on a systematic review, antidepressants modulate esophageal sensation and reduce functional chest pain. There is limited evidence that antidepressants benefit a subgroup of patients with GERD. More controlled trials are needed to investigate the effects of antidepressants on functional esophageal disorders.
Collapse
Affiliation(s)
- Pim W Weijenborg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Heiko S de Schepper
- Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
| |
Collapse
|
|
35
|
Adis Medical Writers. Functional oesophageal disorders must be diagnosed properly and treated accordingly. DRUGS & THERAPY PERSPECTIVES 2015. [DOI: 10.1007/s40267-015-0182-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
36
|
Atluri DK, Chandar AK, Fass R, Falck-Ytter Y. Systematic review with meta-analysis: selective serotonin reuptake inhibitors for noncardiac chest pain. Aliment Pharmacol Ther 2015; 41:167-76. [PMID: 25412947 DOI: 10.1111/apt.13015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 07/17/2014] [Accepted: 10/14/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) are used to treat noncardiac chest pain (NCCP) symptoms, however, data regarding their efficacy remains inconclusive. AIM To conduct a meta-analysis of randomised controlled trials (RCT) comparing SSRIs to placebo in patients with NCCP, and rate the quality of evidence. METHODS Electronic databases were searched using the terms 'noncardiac chest pain', 'atypical chest pain' and 'selective serotonin reuptake inhibitors'. Data were extracted from RCTs of ≥8 weeks. Standardised mean differences (SMD), weighted mean differences (WMD) or risk ratios (RR) were used as summary statistics for pooled outcomes. GRADE methodology was used to rate the quality of evidence. RESULTS Four RCTs (184 patients) met the inclusion criteria. Compared to placebo, patients on SSRIs showed a nonsignificant change in chest pain of 3½ points decrease on a 100 mm visual analogue scale (184 patients, 95% CI, -9.5 to 2.5; I(2) = 0%). Change in depression scores was not significantly different between the two groups (88 patients; WMD = 0.7; 95% CI, -1.81 to 3.20; I(2) = 64%). Treatment discontinuations were not significantly different between groups (154 patients, RR = 2.08; 95% CI, 0.77-5.60; I(2) = 0%). The quality of evidence was rated as moderate for change in chest pain symptoms, low for change in depression scores and moderate for treatment discontinuation due to adverse events. CONCLUSIONS Selective serotonin reuptake inhibitors are not superior to placebo in improving chest pain or depression symptoms in patients with noncardiac chest pain. Larger trials with longer follow-up periods are necessary to assess the benefits and drawbacks of SSRIs for the treatment of noncardiac chest pain.
Collapse
Affiliation(s)
- D K Atluri
- University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | | | | | | |
Collapse
|
|
37
|
Jing F, Zhang J. Metabolic kinetics of 5-hydroxytryptamine and the research targets of functional gastrointestinal disorders. Dig Dis Sci 2014; 59:2642-8. [PMID: 24916714 DOI: 10.1007/s10620-014-3244-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 06/03/2014] [Indexed: 12/13/2022]
Abstract
5-Hydroxytryptamine (5-HT) is an important neurotransmitter in both the central and enteric nervous systems. It has diverse functions in regulating gastrointestinal motility and visceral sensitivity, emotion, appetite, pain and sensory perception, cognition, sexual activity and sleep. These functions are mainly associated with the metabolic kinetics of 5-HT in different tissues. Tryptophan hydroxylase is the rate-limiting enzyme and modulates serotonin synthesis. Vesicular monoamine transporter 1 plays a role in 5-HT storage and release. Degradation of 5-HT is mediated by monoamine oxidase-A. All these factors influence the action of 5-HT in vivo. Functional gastrointestinal disorders (FGIDs) are characterized by a series of symptoms including abdominal pain, diarrhea, constipation, anxiety and depression, in the absence of identifiable structural or biochemical abnormalities. They are frequently accompanied by changed gut motility or visceral sensitivity. An increasing body of research has found FGIDs to be closely associated with 5-HT, and drugs such as citalopram, paroxetine, venlafaxine, alosetron, tegaserod, prucalopride and mosapride have all been developed or discovered from the perspective of the metabolic kinetics of 5-HT. This review discusses the relationship between the metabolic kinetics of 5-HT and research targets in the field of FGIDs and suggests areas of future study that may be useful for understanding these disorders and identification of potential therapeutic targets.
Collapse
Affiliation(s)
- Fuchun Jing
- Department of Gastroenterology, Second Hospital Affiliated to the Medical School, Xi'an Jiaotong University, No. 157, West Road 5, Xi'an City, 710004, Shaanxi Province, China,
| | | |
Collapse
|
|
38
|
|
|
39
|
Coss-Adame E, Erdogan A, Rao SSC. Treatment of esophageal (noncardiac) chest pain: an expert review. Clin Gastroenterol Hepatol 2014; 12:1224-45. [PMID: 23994670 PMCID: PMC3938572 DOI: 10.1016/j.cgh.2013.08.036] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2012] [Revised: 08/13/2013] [Accepted: 08/19/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chest pain is a common and frightening symptom. Once cardiac disease has been excluded, an esophageal source is most likely. Pathophysiologically, gastroesophageal reflux disease, esophageal dysmotility, esophageal hypersensitivity, and anxiety disorders have been implicated. However, treatment remains a challenge. Here we examined the efficacy and safety of various commonly used modalities for treatment of esophageal (noncardiac) chest pain (ECP) and provided evidence-based recommendations. METHODS We reviewed the English language literature for drug trials evaluating treatment of ECP in PubMed, Cochrane, and MEDLINE databases from 1968-2012. Standard forms were used to abstract data regarding study design, duration, outcome measures and adverse events, and study quality. RESULTS Thirty-five studies comprising various treatments were included and grouped under 5 broad categories. Patient inclusion criteria were extremely variable, and studies were generally small with methodological concerns. There was good evidence to support the use of omeprazole and fair evidence for lansoprazole, rabeprazole, theophylline, sertraline, trazodone, venlafaxine, imipramine, and cognitive behavioral therapy. There was poor evidence for nifedipine, diltiazem, paroxetine, biofeedback therapy, ranitidine, nitrates, botulinum toxin, esophageal myotomy, and hypnotherapy. CONCLUSIONS Ideally, treatment of ECP should be aimed at correcting the underlying mechanism(s) and relieving symptoms. Proton pump inhibitors, antidepressants, theophylline, and cognitive behavioral therapy appear to be useful for the treatment of ECP. However, there is urgent and unmet need for effective treatments and for rigorous, randomized controlled trials.
Collapse
Affiliation(s)
- Enrique Coss-Adame
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia
| | - Askin Erdogan
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia
| | - Satish S C Rao
- Section of Gastroenterology and Hepatology, Georgia Regents University, Augusta, Georgia.
| |
Collapse
|
|
40
|
Abstract
The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.
Collapse
Affiliation(s)
- Guy Boeckxstaens
- Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| |
Collapse
|
|
41
|
Dickman R, Maradey-Romero C, Fass R. The role of pain modulators in esophageal disorders - no pain no gain. Neurogastroenterol Motil 2014; 26:603-10. [PMID: 24750261 DOI: 10.1111/nmo.12339] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 03/11/2014] [Indexed: 01/25/2023]
Abstract
Pain modulators have been primarily used for the management of functional esophageal disorders. Recently, these drugs have also been used for the management of other esophageal disorders, such as non-erosive reflux disease, the hypersensitive esophagus, and heartburn that is not responsive to proton pump inhibitor treatment. Several etiologies have been identified in patients with functional esophageal disorders, and these include esophageal hypersensitivity due to peripheral and/or central sensitisation, altered central processing of peripheral stimuli, altered autonomic activity, and psychological comorbidity such as depression and anxiety. Different antidepressants have been used as pain modulators and have demonstrated a beneficial effect on patients with the aforementioned esophageal disorders. Tricyclic antidepressants are the most commonly used class of drugs in clinical practice. Other antidepressants that have been used, some with more clinical success than others, include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and trazodone. Other medications that have been used as pain modulators in esophageal disorders include adenosine antagonists, serotonin agonists, antiepileptics, and medications that ameliorate peripheral neuropathy. The mechanism by which many of the pain modulators confer their visceral analgesic effect remains to be fully elucidated. Regardless, their role and value in treating esophageal disorders have markedly increased in the last decade.
Collapse
Affiliation(s)
- R Dickman
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | | | | |
Collapse
|
|
42
|
Locke GR, Horwhat J, Mashimo H, Savarino E, Zentilin P, Savarino V, Zerbib F, Armbruster SP, Wong RK, Moawad F. Endotherapy for and tailored approaches to treating GERD, and refractory GERD. Ann N Y Acad Sci 2013; 1300:166-186. [PMID: 24117641 DOI: 10.1111/nyas.12240] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This paper presents commentaries on how endoluminal antireflux procedures compare to laparoscopic fundoplication; new endoscopic procedures being studied to treat refractory gastroesophageal reflux disease (GERD); the new Stretta; the relationship between obesity and proton pump inhibitor (PPI) resistance; data concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing refractory GERD; whether microscopic esophagitis is relevant in determining symptoms of non-erosive reflux disease (NERD); how concomitant functional gastrointestinal disorders affect the PPI response in NERD; the evidence that a functional esophagus is associated with inflammatory bowel syndrome (IBS); the role of GABA agonists in the treatment of refractory GERD; the role of biofeedback and antidepressants in refractory GERD; and endoluminal fundoplication using the EsophyX device.
Collapse
Affiliation(s)
- G Richard Locke
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John Horwhat
- Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Hiroshi Mashimo
- VA Boston Healthcare System/Harvard Medical School, Boston, Massachusetts
| | - Edoardo Savarino
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | | | | | - Frank Zerbib
- Department of Gastroenterology, CHU Bordeaux, Saint Andre Hospital, Bordeaux, France
| | - Steven P Armbruster
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Roy K Wong
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Fouad Moawad
- Department of Gastroenterology, Walter Reed National Military Medical Center, Bethesda, Maryland
| |
Collapse
|
|
43
|
Martinucci I, de Bortoli N, Savarino E, Nacci A, Romeo SO, Bellini M, Savarino V, Fattori B, Marchi S. Optimal treatment of laryngopharyngeal reflux disease. Ther Adv Chronic Dis 2013; 4:287-301. [PMID: 24179671 DOI: 10.1177/2040622313503485] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies.
Collapse
|
|
44
|
de Bortoli N, Martinucci I, Bellini M, Savarino E, Savarino V, Blandizzi C, Marchi S. Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome. World J Gastroenterol 2013; 19:5787-5797. [PMID: 24124323 PMCID: PMC3793133 DOI: 10.3748/wjg.v19.i35.5787] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Revised: 11/14/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023] Open
Abstract
Several studies indicate a significant degree of overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both functional heartburn (FH) and IBS are functional digestive disorders that may occur in the same patients. However, data establishing a solid link between FH and IBS are lacking, mainly because the clinical definition of FH has undergone substantial changes over the years. The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS. In particular, several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH (as defined by the Rome III criteria) from GERD via pathophysiological investigations. Independent of these critical issues, there is preliminary evidence supporting a significant degree of FH-IBS overlap. This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications, particularly to distinguish FH from GERD. This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.
Collapse
|
|
45
|
Sanna L, Stuart AL, Berk M, Pasco JA, Girardi P, Williams LJ. Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women. BMC Psychiatry 2013; 13:194. [PMID: 23883104 PMCID: PMC3751862 DOI: 10.1186/1471-244x-13-194] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 06/05/2013] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women. METHODS This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented. RESULTS Current psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0). CONCLUSIONS These results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.
Collapse
Affiliation(s)
- Livia Sanna
- Unit of Psychiatry, Neurosciences, Mental Health and Sensory Organs Department (NeSMOS), Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia
| | - Amanda L Stuart
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia
| | - Michael Berk
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, Australia
- Orygen Youth Health Research Centre, Parkville, Australia
| | - Julie A Pasco
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia
- Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia
- NorthWest Academic Centre, Department of Medicine, The University of Melbourne, Western Health, St Albans, Australia
- Department of Medicine, Barwon Health, Geelong, Australia
| | - Paolo Girardi
- Unit of Psychiatry, Neurosciences, Mental Health and Sensory Organs Department (NeSMOS), Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Lana J Williams
- IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 281, Geelong 3220, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, Australia
| |
Collapse
|
|
46
|
Kumar AR, Katz PO. Functional esophageal disorders: a review of diagnosis and management. Expert Rev Gastroenterol Hepatol 2013; 7:453-61. [PMID: 23899284 DOI: 10.1586/17474124.2013.811028] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Functional esophageal disorders are a group of conditions that present with symptoms presumed to originate in the esophagus and otherwise not detected in an objective manner with available diagnostic tests. The diagnosis is typically made after the exclusion of gastroesophageal reflux disease and a primary esophageal motility abnormality such as achalasia or distal esophageal spasm. Functional heartburn, functional chest pain of presumed esophageal origin, functional dysphagia and globus are the four functional esophageal disorders as defined in the ROME III consensus criteria. The dietary, pharmacological and psychological therapies that are used for managing these difficult-to-treat conditions are based on limited evidence as of this date. Although diagnostic algorithms can separate hypersensitive esophagus from functional esophageal disorders, a therapeutic and most likely a pathophysiologic overlap between these conditions may exist. In this comprehensive review, the authors present an overview of diagnostic approaches to each of these functional esophageal disorders and summarize available evidence on existing management strategies.
Collapse
Affiliation(s)
- Anand R Kumar
- Department of Gastroenterology, Einstein Medical Center, Philadelphia, PA 19141, USA.
| | | |
Collapse
|
|
47
|
Abstract
Gastro-oesophageal reflux disease is one of the most common disorders of the gastrointestinal tract. Over past decades, considerable shifts in thinking about the disease have taken place. At a time when radiology was the only diagnostic test available, reflux disease was regarded as synonymous with hiatus hernia. After the advent of the flexible endoscope, reflux disease was, for a period, equated to oesophagitis. The introduction of oesophageal pH monitoring made us believe that reflux disease could be defined by an abnormally high proportion of time with oesophageal pH less than 4. Moreover, the successive arrival of histamine-2-receptor antagonists and proton-pump inhibitors changed our idea of treatment for the disease, with swings from and towards surgery, endoscopic techniques, and alternative pharmaceutical options.
Collapse
Affiliation(s)
- Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | | | | |
Collapse
|
|
48
|
Management of the patient with incomplete response to PPI therapy. Best Pract Res Clin Gastroenterol 2013; 27:401-14. [PMID: 23998978 PMCID: PMC3761380 DOI: 10.1016/j.bpg.2013.06.005] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Accepted: 06/21/2013] [Indexed: 01/31/2023]
Abstract
Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are 'refractory' and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.
Collapse
|
|
49
|
Viazis N, Keyoglou A, Kanellopoulos AK, Karamanolis G, Vlachogiannakos J, Triantafyllou K, Ladas SD, Karamanolis DG. Selective serotonin reuptake inhibitors for the treatment of hypersensitive esophagus: a randomized, double-blind, placebo-controlled study. Am J Gastroenterol 2012; 107:1662-1667. [PMID: 21625270 DOI: 10.1038/ajg.2011.179] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Ambulatory 24-h pH-impedance monitoring can be used to assess the relationship of persistent symptoms and reflux episodes, despite proton pump inhibitor (PPI) therapy. Using this technique, we aimed to identify patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on their symptoms. METHODS Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, and regurgitation), despite PPI therapy twice daily, underwent 24-h pH-impedance monitoring. Distal esophageal acid exposure (% time pH <4) was measured and reflux episodes were classified into acid or non-acid. A positive symptom index (SI) was declared if at least half of the symptom events were preceded by reflux episodes. Patients with a normal distal esophageal acid exposure time, but with a positive SI were classified as having hypersensitive esophagus and were randomized to receive citalopram 20 mg or placebo once daily for 6 months. RESULTS A total of 252 patients (150 females (59.5%); mean age 55 (range 18-75) years) underwent 24-h pH-impedance monitoring. Two hundred and nineteen patients (86.9%) recorded symptoms during the study day, while 105 (47.9%) of those had a positive SI (22 (20.95%) with acid, 5 (4.76%) with both acid and non-acid, and 78 (74.29%) with non-acid reflux). Among those 105 patients, 75 (71.4%) had normal distal esophageal acid exposure time and were randomized to receive citalopram 20 mg (group A, n=39) or placebo (group B, n=36). At the end of the follow-up period, 15 out of the 39 patients of group A (38.5%) and 24 out of the 36 patients of group B (66.7%) continue to report reflux symptoms (P=0.021). CONCLUSIONS Treatment with SSRIs is effective in a select group of patients with hypersensitive esophagus.
Collapse
Affiliation(s)
- Nikos Viazis
- 2nd Department of Gastroenterology, Evangelismos Hospital, Athens, Greece.
| | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Whorwell PJ. Unraveling functional abdominal bloating and distension: the role of thoraco-abdominal accommodation and a physical sign to aid its detection. Neurogastroenterol Motil 2012; 24:301-4. [PMID: 22414185 DOI: 10.1111/j.1365-2982.2012.01896.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Bloating and distension are common complaints in patients with irritable bowel syndrome of which the cause has remained elusive, although it has been shown that the obvious explanation of excessive gas is unlikely. The recent application of technologies such as the gas challenge technique, abdominal inductance plethysmography, CT scanning, as well as electromyography of the diaphragm and anterior abdominal wall, have allowed the situation to be slowly unraveled. It is now seems probable that the pathophysiology of bloating and distension are subtly different with the former having a sensory component whereas mechanical factors, such as disordered abdominal accommodation, contribute more to the latter.
Collapse
Affiliation(s)
- P J Whorwell
- Department of Translational Medicine, University of Manchester, UK.
| |
Collapse
|