University of Michigan Department of Psychiatry and Comprehensive Depression Center 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.
University of Michigan Department of Psychiatry and Comprehensive Depression Center 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.
J Psychiatr Res. 2019 Apr;111:59-67. doi: 10.1016/j.jpsychires.2019.01.003. Epub 2019 Jan 4.
Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use as directed' or 'use with caution' test categories) or incongruent ('use with increased caution and with more frequent monitoring' test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).
目前，针对重度抑郁症（MDD）的处方实践仅取得了有限的治疗成功。尽管药物基因组学通过识别不合适的药物可能会改善治疗效果，但迄今为止的研究范围有限。在 Genomics Used to Improve DEpression Decisions（GUIDED）试验中，招募了患有 MDD 的门诊患者（N=1167），这些患者至少对一种抗抑郁药的治疗反应不佳，且有患者或临床医生报告称反应不足。该试验是一项盲法随机对照试验，旨在评估基于药物基因组学的干预措施能否改善治疗效果。患者被随机分配到标准治疗（TAU）或药物基因组学指导的干预组。在干预组中，临床医生可以获得药物基因组学检测报告，以便选择合适的药物（指导护理）。将药物与检测结果进行比较，结果分为相符（“按指示使用”或“谨慎使用”）和不相符（“谨慎使用，并增加监测”）。在第 8 周后，对患者进行去盲。主要疗效终点为第 8 周时的症状改善（汉密尔顿抑郁量表 17 项评分[HAM-D17]的变化）；次要疗效终点为第 8 周时的应答（HAM-D17 降低≥50%）和缓解（HAM-D17≤7）。在第 8 周时，指导护理组的症状改善与 TAU 组无显著差异（27.2%比 24.4%，p=0.107）；然而，应答（26.0%比 19.9%，p=0.013）和缓解（15.3%比 10.1%，p=0.007）的改善具有统计学意义。在基线前服用不相符药物的患者，在第 8 周时改用相符药物，其症状改善（33.5%比 21.1%，p=0.002）、应答（28.5%比 16.7%，p=0.036）和缓解（21.5%比 8.5%，p=0.007）更为显著。与持续不相符的患者相比，药物基因组学检测并未显著改善平均症状，但确实提高了标准治疗基础上的难治性抑郁症患者的应答和缓解率（ClinicalTrials.gov 注册号：NCT02109939）。
