BrainDrugs, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
BMC Psychiatry. 2023 Mar 9;23(1):151. doi: 10.1186/s12888-023-04618-x.
Major Depressive Disorder (MDD) is a heterogenous brain disorder, with potentially multiple psychosocial and biological disease mechanisms. This is also a plausible explanation for why patients do not respond equally well to treatment with first- or second-line antidepressants, i.e., one-third to one-half of patients do not remit in response to first- or second-line treatment. To map MDD heterogeneity and markers of treatment response to enable a precision medicine approach, we will acquire several possible predictive markers across several domains, e.g., psychosocial, biochemical, and neuroimaging.
All patients are examined before receiving a standardised treatment package for adults aged 18-65 with first-episode depression in six public outpatient clinics in the Capital Region of Denmark. From this population, we will recruit a cohort of 800 patients for whom we will acquire clinical, cognitive, psychometric, and biological data. A subgroup (subcohort I, n = 600) will additionally provide neuroimaging data, i.e., Magnetic Resonance Imaging, and Electroencephalogram, and a subgroup of patients from subcohort I unmedicated at inclusion (subcohort II, n = 60) will also undergo a brain Positron Emission Tomography with the [C]-UCB-J tracer binding to the presynaptic glycoprotein-SV2A. Subcohort allocation is based on eligibility and willingness to participate. The treatment package typically lasts six months. Depression severity is assessed with the Quick Inventory of Depressive Symptomatology (QIDS) at baseline, and 6, 12 and 18 months after treatment initiation. The primary outcome is remission (QIDS ≤ 5) and clinical improvement (≥ 50% reduction in QIDS) after 6 months. Secondary endpoints include remission at 12 and 18 months and %-change in QIDS, 10-item Symptom Checklist, 5-item WHO Well-Being Index, and modified Disability Scale from baseline through follow-up. We also assess psychotherapy and medication side-effects. We will use machine learning to determine a combination of characteristics that best predict treatment outcomes and statistical models to investigate the association between individual measures and clinical outcomes. We will assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome.
The BrainDrugs-Depression study is a real-world deep-phenotyping clinical cohort study of first-episode MDD patients.
Registered at clinicaltrials.gov November 15th, 2022 (NCT05616559).
重度抑郁症（MDD）是一种异质性的脑部疾病，可能存在多种心理社会和生物学的疾病机制。这也可以解释为什么患者对一线或二线抗抑郁药的治疗反应并不相同，即三分之一至一半的患者对一线或二线治疗没有缓解。为了绘制 MDD 的异质性和治疗反应的标志物，以实现精准医学的方法，我们将在丹麦首都地区的六个公共门诊中，针对 18-65 岁首次发作的抑郁症成年患者，获取多个可能的预测标志物，例如心理社会、生化和神经影像学。
所有患者在接受标准的成人首次发作抑郁症治疗方案之前，都要在丹麦首都地区的六个公共门诊中进行检查。我们将从该人群中招募 800 名患者，对他们进行临床、认知、心理计量和生物学数据的采集。一个亚组（亚组 I，n=600）还将提供神经影像学数据，即磁共振成像和脑电图，而亚组 I 中未服药的患者亚组（亚组 II，n=60）也将接受正电子发射断层扫描，用 [C]-UCB-J 示踪剂与突触前糖蛋白-SV2A 结合。亚组分配基于资格和参与意愿。治疗方案通常持续六个月。在治疗开始后 6、12 和 18 个月，使用贝克抑郁自评量表（QIDS）评估抑郁严重程度。主要结局是 6 个月时的缓解（QIDS≤5）和临床改善（QIDS 降低≥50%）。次要终点包括 12 个月和 18 个月时的缓解率和 QIDS、10 项症状清单、5 项世界卫生组织幸福感指数和改良残疾量表的变化率。我们还评估心理治疗和药物副作用。我们将使用机器学习来确定预测治疗效果的最佳特征组合，并使用统计模型来研究个体测量值与临床结果之间的关联。我们将使用路径分析来评估患者特征、治疗选择和临床结果之间的关联，使我们能够估计治疗选择和时间对临床结果的影响。
BrainDrugs-Depression 研究是一项针对首次发作的 MDD 患者的真实世界的深度表型临床队列研究。
于 2022 年 11 月 15 日在 clinicaltrials.gov 注册（NCT05616559）。
