A review of the use of clozapine levels to guide treatment and determine cause of death

Stark, Anne and Scott, James (2012) A review of the use of clozapine levels to guide treatment and determine cause of death. Australian and New Zealand Journal of Psychiatry, 46 9: 816-825. doi:10.1177/0004867412438871

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Author Stark, Anne
Scott, James
Title A review of the use of clozapine levels to guide treatment and determine cause of death
Journal name Australian and New Zealand Journal of Psychiatry   Check publisher's open access policy
ISSN 0004-8674
1440-1614
Publication date 2012-01-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1177/0004867412438871
Volume 46
Issue 9
Start page 816
End page 825
Total pages 10
Place of publication London, United Kingdom
Publisher Sage Publications
Collection year 2013
Language eng
Formatted abstract
Objective: 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.

Methods: MEDLINE was searched in December 2010 using the following keywords: ‘clozapine levels’, ‘clozapine and toxicity’, ‘clozapine and death’, ‘clozapine and mortality’ and ‘post-mortem redistribution’. Data was also collected from the 2010 MIMS Annual.

Results: 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 µg/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 µg/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 µg/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.

Conclusions: The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 µg/L and 1000 µg/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 (> 600 mg/day) of clozapine, (ii) there has been a change in a patient’s 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.
Keyword Clozapine
Toxicity
Levels
Mortality
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Authors prepress title: "A review of the use of clozapine levels to guide therapy and predict toxicity in treatment and post-mortem".

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
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Created: Thu, 26 Apr 2012, 21:38:00 EST by James Scott on behalf of Psychiatry - Royal Brisbane and Women's Hospital