{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:19:54Z","timestamp":1787905194258,"version":"build-2784847793"},"reference-count":40,"publisher":"Royal College of Psychiatrists","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"abstract":"<jats:sec id=\"S0007125026107260_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clozapine is the gold standard for treatment-resistant schizophrenia, but its use is constrained by the risk of severe neutropenia, thus requiring mandatory lifelong hematological monitoring in many jurisdictions. However, a significant evidence gap persists regarding the long-term comparative risk profiles of clozapine versus other second-generation antipsychotics (SGAs), complicating shared decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107260_as2\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To compare the risk of neutropenia associated with clozapine versus non-clozapine SGAs, assess temporal risk evolution and identify high-risk subgroups to optimise monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107260_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study used Hong Kong\u2019s electronic health records to identify patients initiating clozapine or non-clozapine SGAs (2003\u20132019), with follow-up until 2023. Outcomes included minor (absolute neutrophil count (ANC) 1.0\u20131.5 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/litre) and serious neutropenia (ANC &lt;1.0 \u00d7 10\n                      <jats:sup>9<\/jats:sup>\n                      \/litre). Serious neutropenia leading to clozapine discontinuation within 6 weeks was considered clozapine-associated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107260_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 4868 clozapine and 38 277 non-clozapine SGA users, clozapine users showed higher unadjusted incidences of minor (7.05\n                      <jats:italic>v<\/jats:italic>\n                      . 3.74%) and serious neutropenia (2.53\n                      <jats:italic>v<\/jats:italic>\n                      . 1.45%). However, adjusted rates of serious neutropenia were similar between groups (0.37\n                      <jats:italic>v<\/jats:italic>\n                      . 0.36 per 100 person-years). Clozapine was associated with higher risks of minor (incidence rate ratio (IRR) 5.91; 95% CI 3.96\u20138.70) and serious neutropenia (IRR 3.48; 1.70\u20136.84) in the first 18 weeks. Bayesian change-point analysis showed sharply declining clozapine-associated risk after 26\u201329 weeks, converging with non-clozapine SGAs by 82\u2013135 weeks (around 2 years). No significant early excess risk was found in patients younger than 45, while males experienced a transient risk of minor neutropenia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125026107260_as5\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The risk of clozapine-associated neutropenia is highest in the initial 18 weeks, declining to levels seen with non-clozapine SGAs by 2 years. Weekly monitoring for 18 weeks and monthly for up to 2 years is advisable, with potential for personalised schedules based on age and sex.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2026.10726","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:03:41Z","timestamp":1787904221000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Incidence of clozapine-associated neutropenia in patients with schizophrenia: 20-year population-based study in Hong Kong"],"prefix":"10.1192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-9735","authenticated-orcid":false,"given":"Huiquan","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02zhqgq86","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Luo","sequence":"additional","affiliation":[{"name":"University of Waterloo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-9216","authenticated-orcid":false,"given":"Dan","family":"Siskind","sequence":"additional","affiliation":[{"name":"University of Queensland"},{"name":"Metro South Health"},{"name":"Queensland Centre for Mental Health Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korinne","family":"Northwood","sequence":"additional","affiliation":[{"name":"University of Queensland"},{"name":"Metro South Health"},{"name":"Queensland Centre for Mental Health Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-1713","authenticated-orcid":false,"given":"Jennifer Yee-Man","family":"Tang","sequence":"additional","affiliation":[{"name":"The Chinese University of Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-6244","authenticated-orcid":false,"given":"Simon S. Y.","family":"Lui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02zhqgq86","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H. 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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-ShareAlike licence (https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/), which permits re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is used to distribute the re-used or adapted article and 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"}]}}