{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:46:42Z","timestamp":1789048002047,"version":"build-2803163510"},"reference-count":101,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T00:00:00Z","timestamp":1328832000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Aust N Z J Psychiatry"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To review the literature to examine the use of clozapine levels to (i) guide therapy and prevent toxicity in clinical care and (ii) determine cause of death in post-mortem examination of patients who were treated with clozapine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>MEDLINE was searched in December 2010 using the following keywords: \u2018clozapine levels\u2019, \u2018clozapine and toxicity\u2019, \u2018clozapine and death\u2019, \u2018clozapine and mortality\u2019 and \u2018post-mortem redistribution\u2019. Data was also collected from the 2010 MIMS Annual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The literature reported significant variation in clozapine levels attained with any given dose, and considerable variability in the clinical response achieved at any given clozapine level. The lowest effective clozapine levels ranged from 250 to 550 \u00b5g\/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 \u00b5g\/L. There was minimal correlation between clozapine levels and side effects, with the exception of sedation, hypotension and seizure activity. The risk of seizures increased with plasma clozapine levels greater than 600 \u00b5g\/L or rapid upward titration. In addition to prescribed dose, there are many factors that influence plasma clozapine levels. After death, the process of post-mortem drug redistribution resulted in 3.00 to 4.89 times increases in clozapine levels in central blood vessels and 1.5 fold increases in peripheral vessels compared to ante-mortem levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 \u00b5g\/L and 1000 \u00b5g\/L achieved with gradual upward titration are more likely to be effective and less likely to cause toxicity. Ongoing clozapine level monitoring is indicated, especially when (i) prescribing higher doses (&gt; 600 mg\/day) of clozapine, (ii) there has been a change in a patient\u2019s concomitant pharmacotherapy or cigarette use and (iii) there has been a suboptimal response to treatment. The use of post-mortem clozapine levels to determine clozapine toxicity as a cause of death is unreliable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0004867412438871","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T00:01:54Z","timestamp":1328918514000},"page":"816-825","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":83,"title":["A review of the use of clozapine levels to guide treatment and determine cause of death"],"prefix":"10.1177","volume":"46","author":[{"given":"Anne","family":"Stark","sequence":"first","affiliation":[{"name":"Metro North Mental Health, Royal Brisbane and Women\u2019s Hospital, Herston, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Scott","sequence":"additional","affiliation":[{"name":"Metro North Mental Health, Royal Brisbane and Women\u2019s Hospital, Herston, 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