PDF(Pubmed)
Abstract：
Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.
摘要：
特异性选择性5-羟色胺再摄取抑制剂（SSRIs）代谢受到两种药物的强烈影响，CYP2D6和CYP2C19。然而,在常规临床实践中,前瞻性使用药物遗传学变异体选择或给药SSRIs治疗抑郁症的有效性尚不确定.这个前景的目标，多中心，实用性随机对照试验旨在确定8岁或以上且有≥3个月抑郁症状需要新治疗或修订治疗的参与者的基因型指导选择和抗抑郁药给药剂量对控制抑郁的有效性.那些随机分配到干预组的人在基线时接受药物遗传学测试，并根据可操作的表型接受药房咨询和/或自动临床决策支持干预。而那些随机分配到对照组的人在6个月结束时进行药物遗传学测试。在这两组中,抑郁和药物耐受性结果在基线时评估，1个月,3个月（主要），和6个月。主要终点由3个月时与基线相比评估的患者报告结果测量信息系统(PROMIS)抑郁评分的变化来定义。次要终点包括抑郁症严重程度的住院患者健康问卷（PHQ-8）测量，由PROMIS评分<16定义的缓解率，药物依从性，和药物副作用。主要分析将比较具有可操作的CYP2D6或CYP2C19遗传结果或CYP2D6药物-药物相互作用的试验组之间的PROMIS评分差异。该试验已经完成了1461名参与者的应计，迄今为止，其中562个被发现具有可操作的表型，后续行动将于2024年4月完成。
