Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
BMJ Open. 2020 Dec 1;10(12):e040119. doi: 10.1136/bmjopen-2020-040119.
Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity.
This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12.
This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences.
NCT04301271, DRKS00021119, EudraCT 2018-002947-27.
重度抑郁症（MDD）和肥胖症都是常见的疾病，在全球范围内都有很大的疾病负担。重要的是，MDD 和肥胖症经常同时发生，每种疾病都会使另一种疾病的发病风险增加约 50%-60%。他汀类药物是最常被开的药物之一，其安全性和疗效已得到充分证实。他汀类药物被推荐用于心血管疾病的一级预防，而心血管疾病与 MDD 和肥胖症都有关。此外，他汀类药物是治疗 MDD 的有前途的候选药物，因为一项针对试点随机对照试验的荟萃分析发现，他汀类药物作为抗抑郁药的辅助治疗具有抗抑郁作用。然而，迄今为止，尚无研究测试他汀类药物在 MDD 合并肥胖症患者中的抗抑郁潜力。重要的是，这是一个治疗难度较大的人群，他们往往表现出 MDD 的慢性病程，并且更有可能对治疗产生抵抗。因此，在这项确证性随机对照试验中，我们将确定在 160 名 MDD 合并肥胖症患者中，与标准抗抑郁药物依他普仑合用辛伐他汀作为附加治疗是否比 12 周时的附加安慰剂更有效。
这是一项随机、安慰剂对照、双盲、多中心、平行组设计（二期）试验方案。160 名 MDD 合并肥胖症患者将按 1:1 随机分为辛伐他汀或安慰剂，作为标准抗抑郁药物依他普仑的附加治疗。主要结局是从基线到第 12 周时蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分的变化。次要结局包括 MADRS 反应（定义为基线时 MADRS 评分降低 50%）、MADRS 缓解（定义为 MADRS 评分<10）、患者自我报告贝克抑郁量表（BDI-II）的平均变化以及从基线到第 12 周时高密度脂蛋白、低密度脂蛋白和总胆固醇的平均变化。
本方案已获得柏林州伦理委员会（Ethik-Kommission des Landes Berlin，参考：19/0226-EK 11）和联邦当局（Bundesinstitut für Arzneimittel und Medizinprodukte（BfArM），参考：4043387）的批准。研究结果将发表在同行评议的期刊上，并将在（国际）会议上展示。
NCT04301271、DRKS00021119、EudraCT 2018-002947-27。
