Clozapine levels and outcomes in Serbian patients with treatment-resistant psychotic disorders previously treated without measuring clozapine levels (CLOSER)

• Published in: Psychiatry research Vol. 339; p. 116070
• Main Authors: de Haas, Hans Joachim, Cohen, Dan, de Koning, Mariken Beatrijs, van Weringh, Geke, Petrovic, Veroljub, de Haan, Lieuwe, Touw, Daan Johannes, Ignjatovic Ristic, Dragana
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.09.2024
• Subjects: Dried blood spot testing; Glasgow antipsychotic side-effects scale for clozapine; Side effects of drugs; Therapeutic drug monitoring; Treatment-resistant schizophrenia; Therapeutic drug monitoring; Glasgow antipsychotic side-effects scale for clozapine; Side effects of drugs; Treatment-resistant schizophrenia; Dried blood spot testing
• ISSN: 0165-1781; 1872-7123; 1872-7123
• DOI: 10.1016/j.psychres.2024.116070

•In our group of patients titrated on clozapine without TDM, clozapine levels varied considerably and only a quarter had levels within the therapeutic range.•No relationship between clozapine levels and side effects as measured by GASS-C was observed.•A weak inverse relationship between clozapine levels and disease severity / functional impairment was observed.•TDM can be used to optimize clozapine titration, but our results suggest that the limits of the therapeutic window and laboratory alert level should not be regarded as absolute. Clozapine remains the only pharmacological treatment option for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) of clozapine is recommended, although evidence for the therapeutic range of 350–600 ng/ml is limited. In various countries including Serbia, TDM of clozapine is not routinely performed. This study evaluated the distribution of clozapine levels and their relationship with clinical outcomes in Serbian patients who had not undergone prior TDM. 140 Patients with treatment-resistant schizophrenia and schizo-affective disorder were enrolled. Clozapine levels were measured by dried blood spot (DBS) analysis. Side effects were evaluated by GASS-c, severity of symptoms and functional impairment with WHODAS, CGI-S and GAF. Of the patients, 51.2% had subtherapeutic levels, 24.8% were in the therapeutic window, and 24% had supratherapeutic levels. Clozapine levels showed no association with side effects and a weak positive association with symptom severity and functional impairment. No serious side effects were observed in patients with clozapine levels surpassing 1000 ng/ml (n = 8). Based on these findings, we propose that the upper limit of the therapeutic range should not be regarded as an absolute barrier, and guidelines should allow for a personalized approach when prescribing clozapine.