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Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients

  • Authors:
    • Veroljub Petrovic
    • Dan Cohen
    • Dragic Bankovic
    • Branimir Radmanovic
    • Dragana Ignjatovic Ristic
  • View Affiliations / Copyright

    Affiliations: Special Hospital for Psychiatric Disorders Kovin, 26220 Kovin, Serbia, Esdege Reigersdaal. J. Oudweg 2, 1703 DE Heerhugowaard, The Netherlands, Faculty of Science, University of Kragujevac, 34000 Kragujevac, Serbia, Faculty of Medical Sciences University of Kragujevac, 34000 Kragujevac, Serbia
    Copyright: © Petrovic et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 14
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    Published online on: November 18, 2025
       https://doi.org/10.3892/br.2025.2087
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Abstract

In numerous countries, including Serbia, therapeutic drug monitoring (TDM) for clozapine is unavailable, leaving dose adjustments based solely on clinical judgment, could increase risk of therapeutic failure or adverse outcomes. The present study aimed to assess associations between clozapine and norclozapine serum concentrations, measured via Dried Blood Spot (DBS), and symptom severity, functioning, disability, and side effects in Serbian inpatients with treatment‑resistant schizophrenia (TRS). In a cross‑sectional design, patients with TRS with ongoing clozapine treatment and who did not meet exclusion criteria, were to be included. For clinical assessments of symptom severity, functionality, disability and side effects, were used: Simplified Interview for Negative and Positive Symptoms (SNAPSI), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), WHO Disability Assessment Schedule (WHODAS) and the Clozapine Adverse Effects Scale (GASS‑C). Spearman's analysis showed no significant correlation between GASS‑C scores and clozapine dose or plasma levels. WHODAS scores showed significant positive correlations with clozapine dose (ρ=0.409, P=0.006), clozapine (ρ=0.333, P=0.038) and norclozapine (ρ=0.481, P=0.002) levels. GAF scores negatively correlated with clozapine (ρ=‑0.354, P=0.027) and norclozapine (ρ=‑0.370, P=0.020). GASS‑C scores were significantly associated with female sex (P=0.003), body mass index (BMI; ρ=‑0.678, P<0.0005) and WHODAS scores (ρ=0.372, P=0.014). Regression analysis identified clozapine dose, clozapine level, BMI, SNAPSI and CGI scores as significantly associated with GASS‑C (P=0.045). Norclozapine, BMI and CGI scores significantly associated with WHODAS (P=0.018). In the present study, it was found that clozapine and norclozapine concentrations are significantly associated with functioning, disability and side effects in patients with TRS treated without TDM. DBS‑based monitoring may offer a valuable alternative for optimizing treatment. Further longitudinal studies are needed to clarify the clinical utility of (nor) clozapine level‑guided care in such settings.
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Copy and paste a formatted citation
Spandidos Publications style
Petrovic V, Cohen D, Bankovic D, Radmanovic B and Ristic DI: Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients. Biomed Rep 24: 14, 2026.
APA
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., & Ristic, D.I. (2026). Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients. Biomedical Reports, 24, 14. https://doi.org/10.3892/br.2025.2087
MLA
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., Ristic, D. I."Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients". Biomedical Reports 24.1 (2026): 14.
Chicago
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., Ristic, D. I."Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients". Biomedical Reports 24, no. 1 (2026): 14. https://doi.org/10.3892/br.2025.2087
Copy and paste a formatted citation
x
Spandidos Publications style
Petrovic V, Cohen D, Bankovic D, Radmanovic B and Ristic DI: Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients. Biomed Rep 24: 14, 2026.
APA
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., & Ristic, D.I. (2026). Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients. Biomedical Reports, 24, 14. https://doi.org/10.3892/br.2025.2087
MLA
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., Ristic, D. I."Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients". Biomedical Reports 24.1 (2026): 14.
Chicago
Petrovic, V., Cohen, D., Bankovic, D., Radmanovic, B., Ristic, D. I."Clozapine (and norclozapine) concentrations are correlated with functioning, disability and side‑effects when patients are treated with clozapine without the availability of therapeutic drug monitoring: A study of treatment-resistant schizophrenia inpatients". Biomedical Reports 24, no. 1 (2026): 14. https://doi.org/10.3892/br.2025.2087
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