Applied pharmacogenetics to predict response to treatment of first psychotic episode: study protocol

Front Psychiatry. 2025 Jan 7:15:1497565. doi: 10.3389/fpsyt.2024.1497565. eCollection 2024.

Abstract

The application of personalized medicine in patients with first-episode psychosis (FEP) requires tools for classifying patients according to their response to treatment, considering both treatment efficacy and toxicity. However, several limitations have hindered its translation into clinical practice. Here, we describe the rationale, aims and methodology of Applied Pharmacogenetics to Predict Response to Treatment of First Psychotic Episode (the FarmaPRED-PEP project), which aims to develop and validate predictive algorithms to classify FEP patients according to their response to antipsychotics, thereby allowing the most appropriate treatment strategy to be selected. These predictors will integrate, through machine learning techniques, pharmacogenetic (measured as polygenic risk scores) and epigenetic data together with clinical, sociodemographic, environmental, and neuroanatomical data. To do this, the FarmaPRED-PEP project will use data from two already recruited cohorts: the PEPS cohort from the "Genotype-Phenotype Interaction and Environment. Application to a Predictive Model in First Psychotic Episodes" study (the PEPs study from the Spanish abbreviation) (N=335) and the PAFIP cohort from "Clinical Program on Early Phases of Psychosis" (PAFIP from the Spanish abbreviation) (N = 350). These cohorts will be used to create the predictor, which will then be validated in a new cohort, the FarmaPRED cohort (N = 300). The FarmaPRED-PEP project has been designed to overcome several of the limitations identified in pharmacogenetic studies in psychiatry: (1) the sample size; (2) the phenotype heterogeneity and its definition; (3) the complexity of the phenotype and (4) the gender perspective. The global reach of the FarmaPRED-PEP project is to facilitate the effective deployment of precision medicine in national health systems.

Keywords: Pharmacogenetics; antipsychotic; personalized medicine; prediction; psychosis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study (PMP21/00085) was funded by Instituto de Salud Carlos III (ISCIII) and funded by the European Union (NextGenerationUE- Recovery and Resilence Facility); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); Catalan Government, the Secretariat of Universities and Research of the Department of Enterprise and Knowledge (2021 SGR 00672). The “Programa Asistencial de las Fases Iniciales de Psicosis” (PAFIP) was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant supports: Instituto de Salud Carlos III (Instituto de Salud Carlos III PI020499, PI050427, PI060507, PI14/00639 and PI14/00918); Plan Nacional de Drogas Research (2005-Orden sco/3246/2004); SENY Fundació (CI 2005–0308007); and Fundación Marqués de Valdecilla (API07/011); ClinicalTrials.gov Identifier: NCT03090490, NCT02916303, NCT02205437, NCT0253249, NCT02858102, NCT02220504, NCT02534363, NCT02526030. The PEPS cohort has been funded by the Ministerio de Economía y Competitividad (PI08/0208; PI11/00325; PI14/00612; PI20/00661; PI20/00661), Instituto de Salud Carlos III – Fondo Europeo de Desarrollo Regional. Unión Europea. Una manera de hacer Europa, Centro de Investigación Biomédica en Red de salud Mental, CIBERSAM.