An overview of the project exploring gene-drug pairs in dose guidance of antidepressants and antipsychotics
探索基因-药物配对在抗抑郁药和抗精神病药物剂量指导中的应用项目概述
探索基因-药物配对在抗抑郁药和抗精神病药物剂量指导中的应用项目概述
R. van Westrhenen1,2, A. Young3, PSY-PGx Consortium
R. van Westrhenen 1,2 ,A. Young 3 ,PSY-PGx 联盟
R. van Westrhenen 1,2 ,A. Young 3 ,PSY-PGx 联盟
1Parnassia Groep, Outpatient Clinic Pharmacogenetics, Amsterdam, Netherlands, 2King's College London, Institute of Psychiatry, Psychology and Neuroscience, LondonUK, United Kingdom, 3Imperial College, Institute of Psychiatry, London, United Kingdom
1 荷兰阿姆斯特丹 Parnassia Groep 门诊药物遗传学诊所, 2 英国伦敦国王学院精神病学、心理学与神经科学研究所, 3 英国伦敦帝国理工学院精神病学研究所
1 荷兰阿姆斯特丹 Parnassia Groep 门诊药物遗传学诊所, 2 英国伦敦国王学院精神病学、心理学与神经科学研究所, 3 英国伦敦帝国理工学院精神病学研究所
Background: Pharmacological treatment is one of the key components in the treatment of mental disorders. Unfortunately, only one-third of patients adequately responds to the initial treatment and adverse effects are very common. Genetic heterogeneity of patients is one of the reasons for the high variability in response and for adverse effects. Pharmacogenetic testing of genes encoding drug-metabolizing enzymes could guide physicians to choose the most appropriate medication and facilitate the dosing process.
背景:药物治疗是精神障碍治疗的关键组成部分之一。遗憾的是,仅三分之一的患者对初始治疗产生充分反应,且不良反应十分常见。患者的遗传异质性是导致疗效差异和不良反应的重要原因之一。对药物代谢酶编码基因进行药物遗传学检测,可指导医生选择最合适的药物并优化给药方案。
背景:药物治疗是精神障碍治疗的关键组成部分之一。遗憾的是,仅三分之一的患者对初始治疗产生充分反应,且不良反应十分常见。患者的遗传异质性是导致疗效差异和不良反应的重要原因之一。对药物代谢酶编码基因进行药物遗传学检测,可指导医生选择最合适的药物并优化给药方案。
Aims & Objectives: The PSY-PGx Consortium, funded by the European Union’s Horizon 2020 Program (EUR ~8 million, 60-month duration, Grant Agreement ID: 945151), aims to provide further evidence to this end, both by conducting a multi-center non-industry sponsored clinical study and by interrogating available large-scale biobank data.
目的与目标:由欧盟"地平线 2020"计划资助的 PSY-PGx 联盟(项目金额约 800 万欧元,周期 60 个月,资助协议编号:945151),旨在通过开展多中心非企业赞助的临床研究,并结合现有大规模生物样本库数据分析,为此提供更多循证依据。
目的与目标:由欧盟"地平线 2020"计划资助的 PSY-PGx 联盟(项目金额约 800 万欧元,周期 60 个月,资助协议编号:945151),旨在通过开展多中心非企业赞助的临床研究,并结合现有大规模生物样本库数据分析,为此提供更多循证依据。
Method: The European Union-funded and researcher-initiated PSY-PGx project was launched in 2021 (https://cordis.europa.eu/project/id/945151). It is the largest non-industry-funded project to implement pharmacogenetics in clinical psychiatry. As part of this project the UK population-based biobank UKB (https://www.ukbiobank.ac.uk), was assessed for the relationship between pharmacogenomics and clinical outcomes in patients with psychiatric disorders6. A medication prescription algorithm will be derived from these data.
方法:由欧盟资助、研究人员发起的 PSY-PGx 项目于 2021 年启动(https://cordis.europa.eu/project/id/945151),这是临床精神病学领域实施药物遗传学的最大规模非企业资助项目。作为该项目组成部分,研究团队基于英国人群生物样本库 UKB(https://www.ukbiobank.ac.uk)评估了精神疾病患者的药物基因组学与临床结局的关联关系 6 ,并将从这些数据中推导出药物处方算法。
方法:由欧盟资助、研究人员发起的 PSY-PGx 项目于 2021 年启动(https://cordis.europa.eu/project/id/945151),这是临床精神病学领域实施药物遗传学的最大规模非企业资助项目。作为该项目组成部分,研究团队基于英国人群生物样本库 UKB(https://www.ukbiobank.ac.uk)评估了精神疾病患者的药物基因组学与临床结局的关联关系 6 ,并将从这些数据中推导出药物处方算法。
Results: Even amongst countries that are governed by the same overarching EU regulations, requirements for ethical approval differ considerably regarding the clinical study. At the time of submission, over 150 patients from four clinical centers were either enrolled in or had already completed the PSY-PGx clinical study. Data will be presented from 11437 mood disorder patients who present medication data from primary care sources. Medication success is defined as >12 weeks continuous antidepressant intake and failure as <6 weeks intake.
结果:即使在遵循相同欧盟法规框架的国家之间,针对该临床研究的伦理审批要求仍存在显著差异。截至投稿时,已有来自四个临床中心的 150 余名患者入组或完成 PSY-PGx 临床研究。研究将展示 11437 名心境障碍患者的基础医疗用药数据,其中药物治疗成功定义为持续服用抗抑郁药物超过 12 周,失败则定义为用药不足 6 周。
结果:即使在遵循相同欧盟法规框架的国家之间,针对该临床研究的伦理审批要求仍存在显著差异。截至投稿时,已有来自四个临床中心的 150 余名患者入组或完成 PSY-PGx 临床研究。研究将展示 11437 名心境障碍患者的基础医疗用药数据,其中药物治疗成功定义为持续服用抗抑郁药物超过 12 周,失败则定义为用药不足 6 周。
Discussion & Conclusions: Further progress and challenges of this international project will be presented at the meeting. The ultimate goal of this research is to develop an algorithm that can predict the most effective medication for individual patients, not just based on their phenotype, but by incorporating a wide range of factors. By identifying the complex interactions between these factors and treatment outcomes, this study seeks to contribute to the field of personalized psychiatric care, offering insights into more tailored and effective treatment strategies for psychiatric disorders.
讨论与结论:本次会议将展示该国际合作项目的进一步进展与面临的挑战。此项研究的最终目标是开发一种算法,不仅能基于患者表型,更能通过整合多种因素来预测对个体患者最有效的药物。通过识别这些因素与治疗结果之间复杂的相互作用,本研究旨在为个性化精神疾病治疗领域作出贡献,为精神障碍提供更具针对性和有效性的治疗策略。
References: 参考文献:
1. PSY-PGx: a new intervention for the implementation of pharmacogenetics in psychiatry. R. van Westrhenen, AH. Young AH, U. Heilbronner, JM., M. Ingelman-Sundberg, M. Jukic, J Kaprio, MJH Kas, R. Moldovan, MM. Nöthen, A. Philipsen, N. Shomron, E. Van der Eycken, E. Vieta, TG Schulze, and The PSY-PGx Consortium, World Psychiatry 2025 (24);1:141-142
1. PSY-PGx:精神病学药物遗传学实施的新干预措施。R. van Westrhenen, AH. Young AH, U. Heilbronner, JM., M. Ingelman-Sundberg, M. Jukic, J Kaprio, MJH Kas, R. Moldovan, MM. Nöthen, A. Philipsen, N. Shomron, E. Van der Eycken, E. Vieta, TG Schulze 及 PSY-PGx 联盟,《世界精神病学》2025 年(24)卷 1 期 141-142 页
2. Editorial: From Trial and Error to Individualised Pharmacogenomics-Based Pharmacotherapy in Psychiatry R. van Westrhenen and M. Ingelman-Sundberg Frontiers in Pharmacology, 2021 doi: 10.3389/fphar.2021.725565
2. 社论:从试错法到基于个体化药物基因组学的精神病学药物治疗 R. van Westrhenen 与 M. Ingelman-Sundberg 《药理学前沿》2021 年 doi: 10.3389/fphar.2021.725565
3.Policy and practice review: A First guideline on the use of pharmacogenetics in clinical psychiatry. R. van Westrhenen e.a. Frontiers in Pharmacology, 2021 doi.org/10.3389/fphar.2021.640032
3.政策与实践综述:临床精神病学中药物遗传学应用的首部指南。R. van Westrhenen 等,《药理学前沿》,2021 年 doi.org/10.3389/fphar.2021.640032
4.Dutch Pharmacogenetics Working Group (DPWG) Guideline for the Gene-Drug Interaction between CYP2C19 and CYP2D6 and SSRIs" M. Nijenhuis e.a. Eur J of Human Gen Nov 2021/doi.org/10.1038/s41431-021-01004-7
4.荷兰药物遗传学工作组(DPWG)指南:CYP2C19 与 CYP2D6 基因与 SSRIs 类药物相互作用。M. Nijenhuis 等,《欧洲人类遗传学杂志》2021 年 11 月/doi.org/10.1038/s41431-021-01004-7
讨论与结论:本次会议将展示该国际合作项目的进一步进展与面临的挑战。此项研究的最终目标是开发一种算法,不仅能基于患者表型,更能通过整合多种因素来预测对个体患者最有效的药物。通过识别这些因素与治疗结果之间复杂的相互作用,本研究旨在为个性化精神疾病治疗领域作出贡献,为精神障碍提供更具针对性和有效性的治疗策略。
References: 参考文献:
1. PSY-PGx: a new intervention for the implementation of pharmacogenetics in psychiatry. R. van Westrhenen, AH. Young AH, U. Heilbronner, JM., M. Ingelman-Sundberg, M. Jukic, J Kaprio, MJH Kas, R. Moldovan, MM. Nöthen, A. Philipsen, N. Shomron, E. Van der Eycken, E. Vieta, TG Schulze, and The PSY-PGx Consortium, World Psychiatry 2025 (24);1:141-142
1. PSY-PGx:精神病学药物遗传学实施的新干预措施。R. van Westrhenen, AH. Young AH, U. Heilbronner, JM., M. Ingelman-Sundberg, M. Jukic, J Kaprio, MJH Kas, R. Moldovan, MM. Nöthen, A. Philipsen, N. Shomron, E. Van der Eycken, E. Vieta, TG Schulze 及 PSY-PGx 联盟,《世界精神病学》2025 年(24)卷 1 期 141-142 页
2. Editorial: From Trial and Error to Individualised Pharmacogenomics-Based Pharmacotherapy in Psychiatry R. van Westrhenen and M. Ingelman-Sundberg Frontiers in Pharmacology, 2021 doi: 10.3389/fphar.2021.725565
2. 社论:从试错法到基于个体化药物基因组学的精神病学药物治疗 R. van Westrhenen 与 M. Ingelman-Sundberg 《药理学前沿》2021 年 doi: 10.3389/fphar.2021.725565
3.Policy and practice review: A First guideline on the use of pharmacogenetics in clinical psychiatry. R. van Westrhenen e.a. Frontiers in Pharmacology, 2021 doi.org/10.3389/fphar.2021.640032
3.政策与实践综述:临床精神病学中药物遗传学应用的首部指南。R. van Westrhenen 等,《药理学前沿》,2021 年 doi.org/10.3389/fphar.2021.640032
4.Dutch Pharmacogenetics Working Group (DPWG) Guideline for the Gene-Drug Interaction between CYP2C19 and CYP2D6 and SSRIs" M. Nijenhuis e.a. Eur J of Human Gen Nov 2021/doi.org/10.1038/s41431-021-01004-7
4.荷兰药物遗传学工作组(DPWG)指南:CYP2C19 与 CYP2D6 基因与 SSRIs 类药物相互作用。M. Nijenhuis 等,《欧洲人类遗传学杂志》2021 年 11 月/doi.org/10.1038/s41431-021-01004-7
In sessions