JMIR Publications

ABSTRACT

Background:

Psychotic disorders, such as schizophrenia, present a significant challenge to healthcare systems due to their high disability rates and treatment costs. With discontinuation rates for antipsychotics reaching over 40% in the first year and 80% after three years, it is crucial to tailor antipsychotic selection and dosing early in treatment. Personalised precision psychiatry, underpinned by pharmacogenetics, holds considerable potential in individualising antipsychotic treatment for patients with first-episode psychosis. The internationally pioneering method called 5SPM (5-Step Precision Medicine) lets the application of pharmacogenetics to clinical practice. The recently launched PRevention and early INTervention in mental health (PRINT) programme in Salamanca, Spain, integrates this method to enhance early intervention for adolescents and young people with first-episode psychosis.

Objective:

The CLinical Utility of early intervention including the 5-Step Precision Medicine (5SPM) Method in first-episode Psychosis (CLUMP) project aims to explore whether an early intervention model of personalised precision psychiatry, including pharmacogenetics, improves adherence to antipsychotic medicines and, therefore, clinical and functional outcomes in young people suffering from the first episode of a psychotic illness.

Methods:

To achieve our objectives, we shall compare adherence to the first prescribed antipsychotic medication and clinical and functional outcomes between patients with first-episode psychosis. We shall compare two cohorts: Cohort one will receive the recently introduced PRINT programme, including the 5-Step Precision Medicine (5SPM) method and cohort two would have received the standard care provided by mental health services before the PRINT programme implementation. The primary outcome to measure treatment adherence will be all-cause discontinuation proportions during one-year follow-up. Secondary outcome measures will include pragmatic efficacy, tolerability, and functional outcome measures. For additional comparative purposes, we shall analyse environmental, clinical and pharmacogenetic information of patients with psychotic disorders of more than five years of evolution and with other mental disorders, whose data are currently stored, and ethically approved for research use. A total of 300 patients will be included in the study. Analyses will include descriptive statistics, comparison tests, Kaplan-Meier survival curves, multivariate log-rank tests, qualitative analysis, and cost-benefit evaluation, among others.

Results:

Ethics approval was obtained in June 2023. Recruitment for the CLUMP project began in January 2025, and enrollment for Cohort 1 will continue until May 2026. All data collection is expected to be completed by June 2027. Data analyses are estimated to take approximately six months. The project is scheduled to conclude on December, 2027.

Conclusions:

The CLUMP project is set to provide the first clear blueprint for implementing and evaluating the impact of personalised precision psychiatry based on pharmacogenetics in the context of early intervention programmes for the benefit of young people suffering from the first episode of a severe mental illness, such as schizophrenia. Clinical Trial: ClinicalTrials.gov NCT06453174; https://clinicaltrials.gov/study/NCT06453174