Plasma clozapine in treatment refractory schizophrenia: what is the target range?
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Authors
Flanagan, Robert James
Obee, Stephen John
Kim, Alice Hyun Min
Every-Palmer, Susanna
Sanchez, Paula Liren Valbuena
Evans, Lauren
Rogers, Jonathan
Reeves, Suzanne
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Issue Date
2025
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Article
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Abstract
BACKGROUND: In treatment-refractory schizophrenia (TRS), a predose plasma concentration of 0.35 mg L -1 is suggested to ensure an adequate trial of clozapine, but the target range may differ between smokers and nonsmokers. METHOD: We studied data from a clozapine therapeutic drug monitoring service, 1993-2017, with respect to age, sex, smoking status, clozapine dose, estimated clozapine treatment duration, plasma clozapine and norclozapine concentrations, and reason for the request. RESULTS: There were 35,147 and 88,279 samples from 8882 women and 20,378 men, respectively, for which reasons for the request were specified (26,572 samples, 2 reasons; 6421, 3 or more reasons). More samples were sent for analysis due to suspected adverse drug reactions (ADRs) from women (5.3 vs 4.7%, P < 0.001). The median minimum duration of clozapine treatment before the suspected reaction was 156 days shorter in nonsmokers than smokers of either sex ( P < 0.001) and shorter in female than male nonsmokers (189 vs 334 d; P < 0.01). The differences in median plasma clozapine concentrations between suspected ADR (1869/4149 samples from women/men, respectively), and control (10,627/25,848 samples from women/men, respectively) groups were small, averaging 0.03 mg L -1 ( P < 0.01), but the median plasma clozapine in the ADR and baseline groups was 0.15 mg L -1 lower in smokers than nonsmokers ( P < 0.001). IMPLICATIONS: The target ranges associated with response to clozapine and minimal ADRs in TRS may be 0.35-0.45 and 0.50-0.60 mg L -1 in smokers and in nonsmokers, respectively. ADRs may occur earlier in treatment in nonsmokers, particularly in women, who in general have higher predose plasma clozapine concentrations than men.
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Journal of Clinical Psychopharmacology
Volume
45
Issue
4