Häberling Isabelle, Berger Gregor, Schmeck Klaus, Held Ulrike, Walitza Susanne
Research Department of Child and Adolescent Psychiatry, University Hospital of Psychiatry Zurich of the University of Zurich, Zurich, Switzerland.
Research Department of Child and Adolescent Psychiatry, Psychiatric University Hospitals Basel, University of Basel, Basel, Switzerland.
Front Psychiatry. 2019 Nov 27;10:863. doi: 10.3389/fpsyt.2019.00863. eCollection 2019.
Depressive disorders in childhood and adolescence are a major health problem and often follow a chronic course with severe consequences in later life. Depressive disorders cause the highest burden of disease in this age group across all medical conditions. Treatment adherence is usually very poor, and the use of antidepressant drugs is heavily debated, as suicidal ideations may increase, in particular in the early phase of treatment. Omega-3 fatty acids rich in eicosapentaenoic acid have shown some promising results in over a dozen small scale randomized controlled trials (RCTs) in adult major depressive disorders, with only very few published RCTs in children and adolescents. High-quality phase III RCTs are missing. The omega-3-pMDD trial is a carefully designed phase III RCT to assess the efficacy and safety of omega-3 fatty acids in the early course of pediatric major depressive disorder (MDD). The study is designed as a multi-center, double-blinded, placebo-controlled, randomized clinical trial enrolling 220 patients aged 8 to 17 years meeting DSM-IV criteria for major depressive disorder of at least moderate symptom severity. After a single-blinded placebo-lead-in phase (7 to 10 days) patients are randomly assigned to omega-3 fatty acids or placebo over 36 weeks. Primary outcomes are changes in depression severity, as well as remission and recovery rates. Secondary outcome measures include the omega-3 index and inflammatory parameters as predictors of response. Data analysis will be performed in the intention-to-treat sample using a (generalized) linear random intercept regression model. Through sampling of blood, hair, saliva, and urine, further putative biological markers for depression and omega-3 fatty response will be investigated. This trial addresses if omega-3 fatty acids play a role in the pathogenesis of pediatric MDDs and have antidepressant properties, in particular in clinically depressed children and adolescents with a pre-existing omega-3 fatty acid deficiency, increased markers of oxidative stress, and/or markers of (low grade) inflammation. The study was approved by the local ethics committees. The results will be published in peer-reviewed journals irrespective of specific outcomes. www.ClinicalTrials.gov, identifier NCT03167307.
儿童和青少年期的抑郁障碍是一个主要的健康问题，通常呈慢性病程，在以后的生活中会产生严重后果。在该年龄组的所有医疗状况中，抑郁障碍导致的疾病负担最高。治疗依从性通常很差，抗抑郁药物的使用也备受争议，因为自杀意念可能会增加，尤其是在治疗的早期阶段。富含二十碳五烯酸的ω-3脂肪酸在十几项针对成人重度抑郁障碍的小规模随机对照试验（RCT）中显示出了一些有前景的结果，而针对儿童和青少年的已发表RCT却非常少。高质量的III期RCT尚缺。ω-3-pMDD试验是一项精心设计的III期RCT，旨在评估ω-3脂肪酸在儿童重度抑郁障碍（MDD）早期病程中的疗效和安全性。该研究设计为一项多中心、双盲、安慰剂对照、随机临床试验，招募220名年龄在8至17岁、符合DSM-IV标准且症状至少为中度严重程度的重度抑郁障碍患者。在单盲安慰剂导入期（7至10天）后，患者在36周内被随机分配至ω-3脂肪酸组或安慰剂组。主要结局是抑郁严重程度的变化以及缓解率和康复率。次要结局指标包括ω-3指数和炎症参数作为反应的预测指标。将使用（广义）线性随机截距回归模型在意向性治疗样本中进行数据分析。通过采集血液、头发、唾液和尿液样本，将进一步研究抑郁和ω-3脂肪酸反应的其他潜在生物标志物。 该试验旨在探讨ω-3脂肪酸是否在儿童MDD的发病机制中起作用并具有抗抑郁特性，特别是在临床上患有MDD且存在ω-3脂肪酸缺乏、氧化应激标志物增加和/或（低度）炎症标志物的儿童和青少年中。 该研究已获得当地伦理委员会的批准。无论具体结果如何，研究结果都将发表在同行评审期刊上。www.ClinicalTrials.gov，标识符NCT03167307。
