■30%至50%的重度抑郁症(MDD)患者对抗抑郁药方案没有足够的反应。常规药物治疗主要针对血清素能大脑信号,但需要更好的工具来预测治疗反应和识别MDD的相关亚组,以支持个性化和机械靶向治疗策略。这项研究的目的是使用神经影像学调查无抗抑郁药的MDD患者,电生理学,分子,认知,和临床检查,并评估其预测SSRI治疗临床反应的能力作为个体或组合预测因子。
■我们将在一项非随机开放临床试验中纳入100名未经治疗的中度至重度抑郁症患者(汉密尔顿抑郁量表17)。我们将从5-羟色胺4受体正电子发射断层扫描(PET)脑部扫描中收集数据,功能磁共振成像(fMRI),脑电图(EEG),认知测试,心理测量,和外周生物标志物,之前(在基线),during,在标准抗抑郁治疗12周后。患者将接受艾司西酞普兰治疗,如果在第4周没有反应或无法容忍的副作用,改用度洛西汀进行二线治疗。与基线相比,我们的主要结果(治疗反应)使用第8周的汉密尔顿抑郁评分子量表6项评分进行评估。在一部分患者中(n=~40),我们将重新评估神经生物学反应(使用PET,功能磁共振成像,和EEG)开始药物抗抑郁治疗后8周,绘制治疗反应的神经生物学特征。来自匹配对照的数据将被收集或已经从其他队列获得。
■在这一庞大的参与者队列中进行随访的广泛研究计划为(a)发现抗抑郁药治疗反应的潜在生物标志物提供了独特的可能性,(b)将调查结果应用于未来的MDD分层,(c)加深对MDD病理生理基础的理解,和(d)揭示推定的生物标志物在8周的药物抗抑郁治疗中如何变化。我们的数据可以为优化MDD治疗的精准医学方法铺平道路,也为未来的研究和数据共享提供了资源。
该研究在启动前已在clinicaltrials.gov注册(NCT02869035;08.16.2016,URL:https://clinicaltrials.gov/ct2/results?cond=&term=NCT02869035&cntry=&state=&city=&dist=)。
UNASSIGNED: Between 30 and 50% of patients with major depressive disorder (MDD) do not respond sufficiently to antidepressant regimens. The conventional pharmacological treatments predominantly target serotonergic brain signaling but better tools to predict treatment response and identify relevant subgroups of MDD are needed to support individualized and mechanistically targeted treatment strategies. The aim of this study is to investigate antidepressant-free patients with MDD using neuroimaging, electrophysiological, molecular, cognitive, and clinical examinations and evaluate their ability to predict clinical response to SSRI treatment as individual or combined predictors.
UNASSIGNED: We will include 100 untreated patients with moderate to severe depression (>17 on the Hamilton Depression Rating Scale 17) in a non-randomized open clinical trial. We will collect data from serotonin 4 receptor positron emission tomography (PET) brain scans, functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), cognitive tests, psychometry, and peripheral biomarkers, before (at baseline), during, and after 12 weeks of standard antidepressant treatment. Patients will be treated with escitalopram, and in case of non-response at week 4 or intolerable side effects, offered to switch to a second line treatment with duloxetine. Our primary outcome (treatment response) is assessed using the Hamilton depression rating subscale 6-item scores at week 8, compared to baseline. In a subset of the patients (n = ~40), we will re-assess the neurobiological response (using PET, fMRI, and EEG) 8 weeks after initiated pharmacological antidepressant treatment, to map neurobiological signatures of treatment responses. Data from matched controls will either be collected or is already available from other cohorts.
UNASSIGNED: The extensive investigational program with follow-up in this large cohort of participants provides a unique possibility to (a) uncover potential biomarkers for antidepressant treatment response, (b) apply the findings for future stratification of MDD, (c) advance the understanding of pathophysiological underpinnings of MDD, and (d) uncover how putative biomarkers change in response to 8 weeks of pharmacological antidepressant treatment. Our data can pave the way for a precision medicine approach for optimized treatment of MDD and also provides a resource for future research and data sharing.
UNASSIGNED: The study was registered at clinicaltrials.gov prior to initiation (NCT02869035; 08.16.2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02869035&cntry=&state=&city=&dist=).