Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1256 Briarcliff Road, Building A, 3rd Floor, Atlanta, GA 30306, USA.
Trials. 2012 Jul 9;13:106. doi: 10.1186/1745-6215-13-106.
Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.
METHODS/DESIGN: Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.
The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.
针对患有重度抑郁症（MDD）的患者，临床医生的治疗选择有限，仅有少量的对照数据可以参考。尽管已经报道了许多推测的治疗反应预测因素，但其中大多数是通过对现有数据集的回顾性分析确定的，并且很少有研究能够以影响临床实践的方式进行复制。在之前研究治疗反应预测因素的研究中，一个主要的混杂因素是患者的治疗史，它可能同时影响感兴趣的预测因素和治疗结果。此外，既往治疗史是选择偏倚的重要来源，从而限制了其普遍性。因此，我们启动了一项随机临床试验，旨在确定从未接受过该疾病治疗的患者对三种 MDD 治疗方法的反应的调节因素。
方法/设计：18-65 岁、中重度、非精神病性 MDD 的治疗初治成年人被平均随机分为三组，进行为期 12 周的治疗：（1）认知行为疗法（CBT，16 次）；（2）度洛西汀（30-60mg/d）；或（3）依西酞普兰（10-20mg/d）。随机分组前，患者接受多项评估，包括静息状态功能磁共振成像（fMRI）、免疫标志物、DNA 和基因表达产物、地塞米松-促皮质素释放激素（Dex/CRH）检测。随机分组前或分组后不久，患者还完成全面的人格评估。在治疗早期进行一次生物学指标（fMRI、免疫标志物和基因表达产物）的重复评估，并在 12 周治疗结束时进行第二次 Dex/CRH 测试。急性治疗阶段结束时缓解的患者有资格进入为期 21 个月的随访阶段，每季度就诊以监测复发情况。未缓解的患者接受第二次为期 12 周的增效治疗，在此期间，他们接受认知行为疗法和抗抑郁药物的联合治疗。将确定总体和治疗特异性效应的主要结局（缓解）的预测因素，并建立一个包含多个预测因素的统计模型来预测结局。
PReDICT 研究评估了可能对治疗结果产生不同影响的生物学、心理和临床因素，这是朝着为 MDD 开发个性化治疗方法迈出的重要一步。确定的预测因素应该有助于指导初始治疗的选择，并识别那些最容易复发的患者，从而需要维持或联合治疗以达到和维持健康状态。
