The effect of body weight changes on total plasma clozapine concentrations determined by applying a statistical model to the data from a double-blind trial

Francisco J. Diaz, Richard C. Josiassen, Jose De Leon

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Purpose/Background Some therapeutic drug monitoring studies suggest that increased weight is associated with small increases in clozapine concentrations. The goal of this study was to reanalyze a US double-blind study using a sophisticated statistical model to test whether weight gains from baseline or increases in percentage of body fat from baseline, computed from a published equation, are associated with increased total plasma clozapine concentrations after controlling for the effects of smoking and sex. Methods/Procedures Using data from a multidosage randomized double-blind US clozapine trial previously published, a random intercept linear model of steady-state total plasma clozapine concentrations was fitted to 424 concentrations from 47 patients. Findings/Results After adjusting for sex and smoking, (1) a 1-kg gain in body weight during clozapine treatment was significantly associated with a 1.4% increase in total plasma clozapine concentrations (95% confidence interval = 0.55 to 2.3) and (2) a 1-point increase in percentage of body fat during clozapine treatment was significantly associated with a 5.4% increase in total clozapine concentration (2.5 to 8.3) in females and 1.4% (-1.1 to 4.0) in males. Implications/Conclusions As hypothesized, weight increases during clozapine treatment, which probably reflect increases in fat tissue, were associated with increases in total plasma concentrations. Pending further replication in other samples, it seems likely that clozapine may deposit in body fat and that this may decrease clozapine clearance. This change may be small in most patients but may be clinically relevant in females with major gains in body fat.

Original languageEnglish
Pages (from-to)442-446
Number of pages5
JournalJournal of Clinical Psychopharmacology
Volume38
Issue number5
DOIs
StatePublished - Oct 1 2018

Bibliographical note

Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc.

Keywords

  • adipose tissue
  • clozapine, blood
  • clozapine, pharmacokinetics
  • obesity
  • weight gain

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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