Clinical implementation of preemptive pharmacogenomics in psychiatry: Τhe "PREPARE" study.

ABSTRACT

PREemptive Pharmacogenomic testing for Preventing Adverse drug REactions (PREPARE) is the first prospective, pre-emptive pharmacogenomic study conducted in Europe, within the frame of the Horizon 2020 program. It aims to determine whether implementing pre-emptive pharmacogenomics (PGx) testing of clinically relevant biomarkers, so as the dose and drug selection to be guided, will result in an overall reduction of both the occurrence and the severity of drug-genotype-associated adverse drug reactions (ADRs). To achieve that, two groups of patients will be recruited; one that will receive treatment according to standard clinical practice and one other that will receive pharmacogenomic-guided treatment. The Laboratory of Pharmacogenomics and Individualized Treatment of the University of Patras, which coordinates and represents Greece in this study, in collaboration with the Department of Psychiatry of the General University Hospital of Patras, the Department of Psychiatry of the Hospital "Attikon" and the Departments of Psychiatry of the Psychiatric Hospital of Athens "Dafni" is going to recruit 1500 psychiatric patients that are going to receive antidepressant or antipsychotic treatment. Our scientific hypothesis is that patients who receive pharmacogenomic guided drug and dose selection will experience 30% less ADRs than patients following standard care. Eligible drugs for inclusion in the PREPARE study, are those for which the clinical decision regarding drug and dose choice can be guided according to the Dutch Pharmacogenomics Working Group Guidelines (DPWG). Overall, 7 antidepressants (citalopram, escitalopram, sertraline, paroxetine, venlafaxine, clomipramine, amitriptyline) and 3 antipsychotics (haloperidol, zuclopenthixol, aripiprazole) related to 17 genetic variations in 2 genes (CYP2D6, CYP2C19) will be examined. Occurrence, severity and causality of adverse drug events (ADEs) will be assessed during monitoring, at month 1 and 3 after starting the index-drug, and at the end of each arm, by using the Common Toxicity Criteria for Adverse Events Scale (CTCAE) and the Liverpool Causality Assessment Tool (LCAT), respectively. The results of our study are expected to significantly contribute to the improvement of psychiatric patients' quality of life, by helping to provide the right drug, to the right dose in terms of efficacy, safety and cost-effectiveness.