{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:32:17Z","timestamp":1789839137982,"version":"4.0.1"},"reference-count":43,"publisher":"Royal College of Psychiatrists","issue":"3","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["BJPsych open"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec id=\"S2056472425000298_as1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>Clozapine-induced gastrointestinal hypomotility (CIGH) can cause constipation, which may progress to ileus, intestinal perforation and other life-threatening conditions. There were at least 527 unique cases of harmful CIGH (172 deaths) assessed by strict criteria in the UK, 1992\u20132017.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472425000298_as2\">\n\t    <jats:title>Aims<\/jats:title>\n\t    <jats:p>To assess the impact of strengthened warnings about the risks of CIGH, such as those issued by the UK Medicines and Healthcare products Regulatory Agency (MHRA) (2017) and the US Food and Drug Administration (2020), on reports of harmful CIGH in the UK.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472425000298_as3\">\n\t    <jats:title>Method<\/jats:title>\n\t    <jats:p>We audited UK MHRA Yellow Card reports recorded as clozapine-related gastrointestinal disorders, 2018\u2013end 2022.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472425000298_as4\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Of 335 unique reports (36 fatal, 26 male) that met initial CIGH criteria, there were 129 (22 fatal, 18 male) that met the final CIGH inclusion criteria. Reports of non-fatal CIGH (final criteria) averaged 26 per year (15 in 2022). Deaths averaged four per year (two in 2022). Where data were available the greatest proportion of deaths occurred after 10\u201314 years of clozapine treatment.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S2056472425000298_as5\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>Publicity aimed at raising awareness of the problem posed by CIGH has been associated with a reduction in harmful CIGH as reported to the UK MHRA since 2017. Continued vigilance is needed to reduce risk. Stopping smoking may pose a particular risk and should be monitored carefully.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1192\/bjo.2025.29","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T13:14:04Z","timestamp":1743426844000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["Clozapine-induced gastrointestinal hypomotility: UK pharmacovigilance reports, 2018\u20132022"],"prefix":"10.1192","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-7463","authenticated-orcid":false,"given":"Robert James","family":"Flanagan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Alfred","family":"Handley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-9741","authenticated-orcid":false,"given":"Susanna","family":"Every-Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"170","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"S2056472425000298_ref23","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby052"},{"key":"S2056472425000298_ref35","first-page":"1748","article-title":"A\u00a0decision support alert for promoting prophylactic laxative use with clozapine","volume":"316","author":"Sundermann","year":"2024","journal-title":"Stud Health Technol Inform"},{"key":"S2056472425000298_ref39","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy12050141"},{"key":"S2056472425000298_ref3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3390\/ijms17060863","article-title":"Prevalence and predictors of clozapine-associated constipation: a systematic review and meta-analysis","volume":"17","author":"Shirazi","year":"2016","journal-title":"Int J Mol Sci"},{"key":"S2056472425000298_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115539"},{"key":"S2056472425000298_ref37","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12259"},{"key":"S2056472425000298_ref15","doi-asserted-by":"publisher","DOI":"10.1097\/01.JAA.0000758220.38067.49"},{"key":"S2056472425000298_ref13","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.5497"},{"key":"S2056472425000298_ref22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ebiom.2016.02.020","article-title":"Clozapine-treated patients have marked gastrointestinal hypomotility, the probable basis of life-threatening gastrointestinal complications: a\u00a0cross sectional study","volume":"5","author":"Every-Palmer","year":"2016","journal-title":"EBioMedicine"},{"key":"S2056472425000298_ref11","unstructured":"11 MHRA. Interactive Drug Analysis Profile: Clozapine. MHRA, 2024 (https:\/\/info.mhra.gov.uk\/drug-analysis-profiles\/dap.html?drug=.\/UK_EXTERNAL\/NONCOMBINED\/UK_NON_000299949199.zip&agency=MHRA [cited 24 September 2024])."},{"key":"S2056472425000298_ref42","unstructured":"42 Flanagan, RJ , Every-Palmer, S. Missed clozapine doses \u2013 time to reconsider the 48-hour rule. 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Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e79"}}