Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, 221 85, Lund, Sweden.
Office for Psychiatry and Habilitation, Psychiatric Clinic Helsingborg, Region Skåne, 252 23, Helsingborg, Sweden.
BMC Psychiatry. 2022 Dec 19;22(1):801. doi: 10.1186/s12888-022-04430-z.
Most antidepressant treatment studies have included patients strictly based on the Diagnostic and Statistical Manual of Mental Disorders definition of Major Depressive Disorder (MDD). Given the heterogeneity of MDD, this approach may have obscured inter-patient differences and hampered the development of novel and targeted treatment strategies. An alternative strategy is to use biomarkers to delineate endophenotypes of depression and test if these can be targeted via mechanism-based interventions. Several lines of evidence suggest that "inflammatory depression" is a clinically meaningful subtype of depression. Preliminary data indicate that omega-3 fatty acids, with their anti-inflammatory and neuroprotective properties, may be efficacious in this subtype of depression, and this study aims to test this hypothesis.
We conduct a match-mismatch-trial to test if add-on omega-3 fatty acid eicosapentaenoic acid (EPA) reduces depressive symptoms in patients with MDD and systemic low-grade inflammation. MDD patients on a stable antidepressant treatment are stratified at baseline on high sensitivity-C-reactive protein (hs-CRP) levels to a high-inflammation group (hs-CRP ≥ 3 mg/L) or a low-inflammation group (hs-CRP < 3 mg/L). Both groups receive add-on EPA (2 g per day) for 8 weeks with three study visits, all including blood draws. Patients and raters are blind to inflammation status. Primary outcome measure is change in Hamilton Depression Rating Scale score between baseline and week 8. We hypothesize that the inflammation group has a superior antidepressant response to EPA compared to the non-inflammation group. Secondary outcomes include a composite score of "inflammatory depressive symptoms", quality of life, anxiety, anhedonia, sleep disturbances, fatigue, cognitive performance and change in biomarkers relating to inflammation, oxidative stress, metabolomics and cellular aging.
In this study we will, for the first time using a match-mismatch trial design, test if omega-3 is an efficacious treatment for inflammatory depression. If our study is successful, it could add to the field of precision psychiatry.
This trial was registered May 8, 2017 on clinicaltrials.gov under the reference number NCT03143075.
大多数抗抑郁治疗研究都严格基于《精神障碍诊断与统计手册》（DSM）对重度抑郁症（MDD）的定义来纳入患者。鉴于 MDD 的异质性，这种方法可能掩盖了患者间的差异，并阻碍了新型和靶向治疗策略的发展。另一种策略是使用生物标志物来描绘抑郁的内表型，并测试这些内表型是否可以通过基于机制的干预来靶向。有几条证据表明，“炎症性抑郁症”是一种有临床意义的抑郁症亚型。初步数据表明，具有抗炎和神经保护特性的ω-3 脂肪酸可能对这种亚型的抑郁症有效，本研究旨在检验这一假设。
我们进行了一项匹配-不匹配试验，以测试补充 ω-3 脂肪酸二十碳五烯酸（EPA）是否能减轻 MDD 合并全身低度炎症患者的抑郁症状。在稳定的抗抑郁治疗基础上，根据高敏 C 反应蛋白（hs-CRP）水平将 MDD 患者分层为高炎症组（hs-CRP≥3mg/L）或低炎症组（hs-CRP<3mg/L）。两组均接受补充 EPA（每天 2 克）治疗 8 周，共进行 3 次研究访视，均包括采血。患者和评估者对炎症状态不知情。主要结局指标是基线至第 8 周汉密尔顿抑郁量表评分的变化。我们假设炎症组对 EPA 的抗抑郁反应优于非炎症组。次要结局包括“炎症性抑郁症状”综合评分、生活质量、焦虑、快感缺失、睡眠障碍、疲劳、认知表现以及与炎症、氧化应激、代谢组学和细胞衰老相关的生物标志物的变化。
在这项研究中，我们将首次使用匹配-不匹配试验设计，测试 ω-3 是否是炎症性抑郁症的有效治疗方法。如果我们的研究成功，它可能会为精准精神病学领域增添新的内容。
该试验于 2017 年 5 月 8 日在 clinicaltrials.gov 上注册，注册号为 NCT03143075。
