{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:26:15Z","timestamp":1792463175290,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T00:00:00Z","timestamp":1526860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clozapine is associated with life\u2010threatening neutropenia. There are no previous meta\u2010analyses of the epidemiology of clozapine\u2010associated neutropenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the cumulative incidence of mild, moderate and severe neutropenia, incidence of death related to severe neutropenia, case fatality rate of neutropenia and the longitudinal incidence of neutropenia following exposure to clozapine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources<\/jats:title>\n                    <jats:p>A systematic search of Medline, EMBASE and PsycINFO using search terms [clozapine OR clopine OR zaponex OR clozaril] AND [neutropenia OR agranulocytosis].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Random effects meta\u2010analysis to determine event rates and longitudinal incidence of events per 100 person\u2010years of exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 108 studies were included. The incidence of clozapine\u2010associated neutropenia was 3.8% (95% CI: 2.7\u20135.2%) and severe neutropenia 0.9% (95% CI: 0.7\u20131.1%). The incidence of death related to neutropenia following prescription of clozapine was 0.013% (95% CI: 0.01\u20130.017%). The case fatality rate of severe neutropenia was 2.1% (95% CI: 1.6\u20132.8%). The peak incidence of severe neutropenia occurred at one month of exposure and declined to negligible levels after one year of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine\u2010associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.12898","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:15:40Z","timestamp":1526948140000},"page":"101-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":229,"title":["Meta\u2010analysis examining the epidemiology of clozapine\u2010associated neutropenia"],"prefix":"10.1111","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1561-581X","authenticated-orcid":false,"given":"N.","family":"Myles","sequence":"first","affiliation":[{"name":"Haematology Directorate SA Pathology Adelaide SA Australia"},{"name":"School of Medicine University of Queensland St Lucia Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Myles","sequence":"additional","affiliation":[{"name":"Country Health Glenside SA 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