{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T19:41:51Z","timestamp":1760816511536,"version":"build-2065373602"},"reference-count":56,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Health Commission Capacity Building and Continuing Education Center Cancer Pain Management","award":["PMT1001-1"],"award-info":[{"award-number":["PMT1001-1"]}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["2022-1-4061"],"award-info":[{"award-number":["2022-1-4061"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3602200","2022YFC3602201","2022YFC3602202","2022YFC3602203","2022YFC3602205"],"award-info":[{"award-number":["2022YFC3602200","2022YFC3602201","2022YFC3602202","2022YFC3602203","2022YFC3602205"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,9]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>As a disorder of gut\u2013brain interaction, irritable bowel syndrome (IBS) is a common reason for patient visits in primary and specialist care settings. IBS is associated with recurrent abdominal pain, altered bowel habit, resulting in alternating constipation and diarrhoea, bloating, without serious organic diseases. The bidirectional relationship between IBS and psychological factor is also complex. Studies have suggested that tricyclic antidepressants can effectively control the concomitant symptoms of IBS, especially some severe and refractory symptoms. At present, the conventional treatment of IBS remains somewhat unsatisfactory. Studies have shown that the antidepressant effects of esketamine are rapid and significant, whether a single low dose of esketamine is effective in IBS deserves further investigation. In this study, we hypothesise that a single low dose of esketamine will be effective for IBS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a single-centre, randomised, double-blind, placebo-controlled trial. Patients with IBS are divided into three levels according to the severity of IBS: mild, moderate and severe. 92 patients in the esketamine group and 92 patients in the control group who are scheduled for colonoscopy will be prospectively recruited in each level. The primary outcome is the IBS Severity Scoring System at baseline and at 3\u2009days, 1\u2009week, 3 weeks, 6 weeks after colonoscopy. The secondary outcome includes IBS-Quality of Life, Bristol Stool Form scale, Hospital Anxiety and Depression Scale, Patient Health Questionnaire-12 Somatic Symptom Score and adverse events. The allocation sequence is assigned by a random number table using a block randomisation method by SPSS (Version 26, IBM Inc., USA) Statistics software. All enrolled patients, anaesthesiologist B and researchers responsible for follow-up and data collection and analysis are therefore fully blinded. All data will be performed using SPSS Statistics software, and a p value &lt;0.05\u2009will be considered statistically significant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The protocol has been approved by the Medical Ethics Committee of Beijing Tiantan Hospital affiliated to Capital Medical University (KY2024-414-02). All participants will sign a written informed consent form. The results will be submitted for publication in peer-reviewed journals, presented at international conferences, and shared with participants via hospital newsletters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>Efficacy of Esketamine for Patients With Irritable Bowel Syndrome (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06788444\">NCT06788444<\/jats:ext-link>).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-099793","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T14:20:18Z","timestamp":1750688418000},"page":"e099793","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of a single low dose of esketamine for patients with irritable bowel syndrome: study protocol for a randomised controlled trial"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06788444","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06788444","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06788444","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Zhe","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Day Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Day Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Day Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-6576","authenticated-orcid":false,"given":"Fang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pain Management, Beijing Tiantan Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"2025101812060206000_15.6.e099793.1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"2025101812060206000_15.6.e099793.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0286-8"},{"key":"2025101812060206000_15.6.e099793.3","article-title":"Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome","volume":"2011","author":"Ruepert","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2025101812060206000_15.6.e099793.4","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001036"},{"key":"2025101812060206000_15.6.e099793.5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323799"},{"key":"2025101812060206000_15.6.e099793.6","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.14256","article-title":"Prevalence and impact of Rome IV versus Rome III irritable bowel syndrome in patients with inflammatory bowel disease","volume":"34","author":"Fairbrass","year":"2022","journal-title":"Neurogastroenterol Motil"},{"key":"2025101812060206000_15.6.e099793.7","doi-asserted-by":"publisher","DOI":"10.1080\/00365520601113927"},{"key":"2025101812060206000_15.6.e099793.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01740.x"},{"key":"2025101812060206000_15.6.e099793.9","first-page":"1246","article-title":"Global prevalence of irritable bowel syndrome","volume":"115","author":"Oka","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"2025101812060206000_15.6.e099793.10","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.163162"},{"key":"2025101812060206000_15.6.e099793.11","first-page":"e45","article-title":"Ketamine restores gut-brain axis homeostasis in IBS patients with comorbid anxiety: a randomized controlled trial","volume":"21","author":"Wang","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025101812060206000_15.6.e099793.12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042320-014032"},{"key":"2025101812060206000_15.6.e099793.13","first-page":"112","article-title":"Long-term outcomes of low FODMAP diet in IBS: high dropout rates limit sustained efficacy","volume":"74","author":"Houte","year":"2025","journal-title":"Gut"},{"key":"2025101812060206000_15.6.e099793.14","first-page":"e789","article-title":"Multimodal anthroposophic therapy vs standard care in refractory IBS: a randomized trial","volume":"166","author":"Hinse","year":"2024","journal-title":"Gastroenterology"},{"key":"2025101812060206000_15.6.e099793.15","first-page":"283","article-title":"Gut-brain axis mechanisms in IBS","volume":"20","author":"Martin","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2025101812060206000_15.6.e099793.16","first-page":"345","article-title":"Gut-brain axis dysregulation in severe IBS: a biomarker study","volume":"168","author":"Jones","year":"2025","journal-title":"Gastroenterology"},{"key":"2025101812060206000_15.6.e099793.17","article-title":"Gut microbiota and metabolomic profiles distinguish IBS subtypes with comorbid depression","volume":"15","author":"Ng","year":"2023","journal-title":"Gut Microbes"},{"key":"2025101812060206000_15.6.e099793.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2007.01409.x"},{"key":"2025101812060206000_15.6.e099793.19","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1517\/13543784.2013.782392","article-title":"Atypical antipsychotics as a possible treatment option for irritable bowel syndrome","volume":"22","author":"Pae","year":"2013","journal-title":"Expert Opin Investig Drugs"},{"key":"2025101812060206000_15.6.e099793.20","first-page":"e789","article-title":"Multidisciplinary treatment for refractory IBS: integration of gut-directed therapy and cognitive behavioral intervention","volume":"20","author":"Simr\u00e9n","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025101812060206000_15.6.e099793.21","first-page":"1376","article-title":"Comparative efficacy of psychological therapies for IBS: a systematic review","volume":"117","author":"Laird","year":"2022","journal-title":"Am J Gastroenterol"},{"key":"2025101812060206000_15.6.e099793.22","first-page":"568","article-title":"Efficacy of antidepressants in IBS","volume":"117","author":"Ford","year":"2022","journal-title":"Am J Gastroenterol"},{"key":"2025101812060206000_15.6.e099793.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01523-4"},{"key":"2025101812060206000_15.6.e099793.24","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-018-0519-3"},{"key":"2025101812060206000_15.6.e099793.25","doi-asserted-by":"publisher","DOI":"10.1177\/2045125316631267"},{"key":"2025101812060206000_15.6.e099793.26","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1177\/0269881120922955","article-title":"Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression","volume":"34","author":"Del Sant","year":"2020","journal-title":"J Psychopharmacol"},{"key":"2025101812060206000_15.6.e099793.27","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060720"},{"key":"2025101812060206000_15.6.e099793.28","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s43440-020-00097-z","article-title":"Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials","volume":"72","author":"Kryst","year":"2020","journal-title":"Pharmacol Rep"},{"key":"2025101812060206000_15.6.e099793.29","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.015198"},{"key":"2025101812060206000_15.6.e099793.30","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19020172"},{"key":"2025101812060206000_15.6.e099793.31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1903305"},{"key":"2025101812060206000_15.6.e099793.32","doi-asserted-by":"crossref","DOI":"10.1186\/s13063-022-06492-6","article-title":"Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care","volume":"23","author":"Alderson","year":"2022","journal-title":"Trials"},{"key":"2025101812060206000_15.6.e099793.33","doi-asserted-by":"publisher","DOI":"10.1053\/J.GASTRO.2016.02.031"},{"key":"2025101812060206000_15.6.e099793.34","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1038\/s41380-024-02857-2","article-title":"Medication use is associated with distinct microbial features in anxiety and depression","volume":"30","author":"Dilmore","year":"2025","journal-title":"Mol Psychiatry"},{"key":"2025101812060206000_15.6.e099793.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2007.00937.x"},{"key":"2025101812060206000_15.6.e099793.36","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1053\/j.gastro.2022.01.021","article-title":"Assessing the Impact of Changes to the Rome IV Criteria for Clinical Practice in Irritable Bowel Syndrome","volume":"162","author":"Black","year":"2022","journal-title":"Gastroenterology"},{"key":"2025101812060206000_15.6.e099793.37","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50055"},{"key":"2025101812060206000_15.6.e099793.38","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-078218","article-title":"Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial","volume":"385","author":"Wang","year":"2024","journal-title":"BMJ"},{"key":"2025101812060206000_15.6.e099793.39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1614.2005.01686.x"},{"key":"2025101812060206000_15.6.e099793.40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1997.142318000.x"},{"key":"2025101812060206000_15.6.e099793.41","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16934"},{"key":"2025101812060206000_15.6.e099793.42","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1016\/j.cgh.2022.03.018","article-title":"Are They Side Effects? Extraintestinal Symptoms Reported During Clinical Trials of Irritable Bowel Syndrome May Be More Severe at Baseline","volume":"20","author":"Ballou","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025101812060206000_15.6.e099793.43","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000002052"},{"key":"2025101812060206000_15.6.e099793.44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05615.x"},{"key":"2025101812060206000_15.6.e099793.45","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018831127942"},{"key":"2025101812060206000_15.6.e099793.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.02.045"},{"key":"2025101812060206000_15.6.e099793.47","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709011203"},{"key":"2025101812060206000_15.6.e099793.48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1983.tb09716.x"},{"key":"2025101812060206000_15.6.e099793.49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04402.x"},{"key":"2025101812060206000_15.6.e099793.50","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-200203000-00008"},{"key":"2025101812060206000_15.6.e099793.51","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s40263-020-00699-4","article-title":"Cardiac Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: Results from the Clinical Development Program","volume":"34","author":"Doherty","year":"2020","journal-title":"CNS Drugs"},{"key":"2025101812060206000_15.6.e099793.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.10.018"},{"key":"2025101812060206000_15.6.e099793.53","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jad.2020.09.056","article-title":"Comparative effectiveness of esketamine in the treatment of anhedonia in bipolar and unipolar depression","volume":"278","author":"Delfino","year":"2021","journal-title":"J Affect Disord"},{"key":"2025101812060206000_15.6.e099793.54","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.neurom.2023.12.004","article-title":"Combination of Acute and Maintenance Esketamine Treatment With Adjunctive Long-Term Vagus Nerve Stimulation in Difficult-to-Treat Depression","volume":"27","author":"Kavakbasi","year":"2024","journal-title":"Neuromodulation"},{"key":"2025101812060206000_15.6.e099793.55","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.21m14318","article-title":"Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression","volume":"83","author":"Williamson","year":"2022","journal-title":"J Clin Psychiatry"},{"key":"2025101812060206000_15.6.e099793.56","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.300.6722.439"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-099793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T19:06:10Z","timestamp":1760814370000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-099793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,23]]},"published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1136\/bmjopen-2025-099793"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-099793","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2025,6]]}}}