Tsermpini E E, Skokou M, Ferentinos P, Georgila E, Gourzis P, Assimakopoulos K, Patrinos G P
Laboratory of Pharmacogenomics and Personalized Treatment, Department of Pharmacy, University of Patras.
Department of Psychiatry, General University Hospital of Patras, University of Patras, Patra.
Psychiatriki. 2020 Oct-Dec;31(4):341-351. doi: 10.22365/jpsych.2020.314.341.
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.
用于预防药物不良反应的前瞻性药物基因组学检测（PREPARE）是在“地平线2020”计划框架内于欧洲开展的首个前瞻性、预防性药物基因组学研究。其目的是确定对临床相关生物标志物进行预防性药物基因组学（PGx）检测，以便指导剂量和药物选择，是否会使药物基因型相关不良反应（ADR）的发生率和严重程度总体降低。为实现这一目标，将招募两组患者；一组将按照标准临床实践接受治疗，另一组将接受药物基因组学指导的治疗。帕特雷大学药物基因组学与个体化治疗实验室在本研究中进行协调并代表希腊，与帕特雷综合大学医院精神科、“阿提康”医院精神科以及雅典“达夫尼”精神病院精神科合作，将招募1500名即将接受抗抑郁药或抗精神病药治疗的精神病患者。我们的科学假设是，接受药物基因组学指导的药物和剂量选择的患者发生的ADR比遵循标准治疗的患者少30%。符合纳入PREPARE研究的药物，是那些根据荷兰药物基因组学工作组指南（DPWG），其药物和剂量选择的临床决策可得到指导的药物。总体而言，将检测与2个基因（CYP2D6、CYP2C19）中的17种基因变异相关的7种抗抑郁药（西酞普兰、艾司西酞普兰、舍曲林、帕罗西汀、文拉法辛、氯米帕明、阿米替林）和3种抗精神病药（氟哌啶醇、珠氯噻醇、阿立哌唑）。在监测期间、开始使用索引药物后的第1个月和第3个月以及每组结束时，将分别使用不良事件通用毒性标准量表（CTCAE）和利物浦因果关系评估工具（LCAT）评估药物不良事件（ADE）的发生率、严重程度和因果关系。我们的研究结果有望通过有助于在疗效、安全性和成本效益方面提供正确的药物和正确的剂量，为改善精神病患者的生活质量做出重大贡献。
