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. 2024 Mar 7;12(3):597.
doi: 10.3390/biomedicines12030597.

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia

Estela Sangüesa  1 , Emilio Fernández-Egea  2   3 , Julia Concha  1 , Cristina B García  1 , María Pilar Ribate  1
Affiliations

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia

Estela Sangüesa et al. Biomedicines. .

Abstract

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

Keywords: antipsychotics; drug response; genetic testing; pharmacodynamics; pharmacogenetic variants; treatment-resistant schizophrenia.

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Conflict of interest statement

E.F.-E. has received consultancy honoraria from Boehringer-Ingelheim (2022), Atheneum (2022) and Rovi (2022), speaker fees by Adamed (2022) and Otsuka (2023) and training and research material from Merz (2020). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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