Winner Joel G, Carhart Joseph M, Altar C Anthony, Allen Josiah D, Dechairo Bryan M
AssureRx Health, Inc., 6030 S. Mason Montgomery Rd., Mason, Ohio 45040, USA.
Discov Med. 2013 Nov;16(89):219-27.
A prospective double-blind randomized control trial (RCT) to evaluate the benefit of a combinatorial, five gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used in the treatment of major depression in an outpatient psychiatric practice.
Depressed adult outpatients were randomized to a treatment as usual (TAU, n=25) arm or a pharmacogenomic-informed GeneSight (n=26) arm. Subjects were blinded to their treatment group and depression severity was assessed by blinded study raters. Within two days of enrollment, clinicians of subjects in the guided group received the GeneSight report that categorized each of 26 psychotropic medications within a green, yellow, or red "bin" based on the relationship of each medication to a subject's pharmacokinetic and pharmacodynamic combinatorial gene variant profile. Antidepressant medication changes began within 2 weeks after baseline assessments. Depression severity was assessed by blinded study raters using the HAMD-17, PHQ-9, QIDS-SR, and QIDS-CR administered 4, 6, and 10 weeks after baseline assessment.
Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08).
Pharmaco-genomic-guided treatment with GeneSight doubles the likelihood of response in all patients with treatment resistant depression and identifies 30% of patients with severe gene-drug interactions who have the greatest improvement in depressive symptoms when switched to genetically suitable medication regimens.
一项前瞻性双盲随机对照试验（RCT），旨在评估一种组合式五基因药物基因组检测及解读报告（GeneSight）在门诊精神科治疗重度抑郁症时使用精神药物管理中的益处。
成年抑郁症门诊患者被随机分为常规治疗组（TAU，n = 25）或药物基因组学指导的GeneSight组（n = 26）。受试者对其治疗组不知情，抑郁严重程度由不知情的研究评估者进行评估。在入组两天内，指导组受试者的临床医生收到GeneSight报告，该报告根据每种药物与受试者的药代动力学和药效学组合基因变异谱的关系，将26种精神药物分别归类为绿色、黄色或红色“类别”。抗抑郁药物的调整在基线评估后2周内开始。在基线评估后4周、6周和10周，由不知情的研究评估者使用汉密尔顿抑郁量表17项版（HAMD - 17）、患者健康问卷9项版（PHQ - 9）、快速抑郁症状问卷-自评（QIDS - SR）和快速抑郁症状问卷-他评（QIDS - CR）评估抑郁严重程度。
观察到组间趋势，在第10周时，通过HAMD - 17测量，GeneSight组的反应和缓解可能性增加了一倍多。GeneSight组在HAMD - 17上抑郁症状的平均改善百分比高于TAU组（30.8%对20.7%；p = 0.28）。在基线时根据个体受试者基因型被开具禁忌药物（即红色类别）的TAU受试者，在第10周时通过HAMD - 17测量的抑郁症状几乎没有改善（0.8%），这远低于开始使用红色类别药物的药物基因组学指导受试者的33.1%的改善（p = 0.06）以及GeneSight组总体26.4%的改善（p = 0.08）。
使用GeneSight进行药物基因组学指导的治疗使所有难治性抑郁症患者的反应可能性增加一倍，并识别出30%存在严重基因-药物相互作用的患者，这些患者在改用基因匹配的药物治疗方案后抑郁症状改善最大。
