OMEGA-3 FOR DEPRESSION AND OTHER CARDIAC RISK FACTORS

OMEGA-3 针对抑郁症和其他心脏危险因素

• 批准号: 8787486
• 负责人: ROBERT M CARNEY
• 金额: $ 70.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8787486
• 关键词: Adverse effects; Antidepressive Agents; Blood; C-reactive protein; Cardiac; Cardiovascular system; Citalopram; Clinical Trials; Coagulation Process; Cognitive Therapy; Control Groups; Controlled Clinical Trials; Coronary heart disease; DSM-IV; Dietary intake; Disease-Free Survival; Docosahexaenoic Acids; Double-Blind Method; Drug Formulations; Eicosapentaenoic Acid; Electrocardiogram; Enrollment; Erythrocytes; Evaluation; Event; Fatty Acids; Fibrinogen; Fluoxetine; Future; Hamilton Rating Scale for Depression; Health; Heart; Heart Diseases; Heart Rate; Hour; Inflammation; Intervention; Lead; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mirtazapine; Monitor; Morbidity - disease rate; Omega-3 Fatty Acids; Outcome; Participant; Patients; Pharmaceutical Preparations; Phospholipids; Placebo Control; Placebos; Plasma; Platelet Factor 4; Population; Publishing; Quality of life; Randomized; Reporting; Research; Risk; Risk Factors; Risk Marker; Sertraline; Severities; TNF gene; Testing; Time; Tumor Necrosis Factor-alpha; acute coronary syndrome; base; capsule; cardiac depression; cardiovascular risk factor; clinical practice; depressed patient; dosage; effective therapy; efficacy testing; efficacy trial; heart rate variability; improved; interpersonal therapy; meetings; mortality; single episode major depressive disorder; standard care; sudden cardiac death; treatment effect

DESCRIPTION (provided by applicant): Depression increases the risk for cardiac morbidity and mortality 2-4 fold in patients with coronary heart disease (CHD). Recent clinical trials have tested standard treatments for comorbid depression in patients with CHD, and some have evaluated their effects on cardiac morbidity and mortality. Most of these trials have shown that standard treatments have only modest effects on depression and have produced relatively small differences between the intervention and control condition. Consequently, they have been unable to determine whether effective treatment of depression can improve cardiac outcomes. Low dietary intake and low plasma phospholipid or erythrocyte levels of two omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with depression and other cardiac risk markers, including ones that may mediate the relationship between depression and cardiac mortality. There is growing evidence from small psychiatric trials that the efficacy of standard antidepressants can be improved by coadministration of an omega-3 FA formulation containing at least 1 gram of EPA with a ratio of between 2 to 4 parts EPA to 1 part DHA (2-4EPA:1DHA). The purpose of the proposed research is to determine whether antidepressant augmentation with this omega-3 FA formulation is superior to antidepressant therapy alone for major depression in patients with CHD, and to investigate its effects on other cardiac risk markers in these patients. The proposed study is a randomized, placebo-controlled, double-blind clinical trial. Patients who meet the DSM-IV-TR criteria for a major depressive episode 2-4 months after an acute coronary syndrome (ACS) will be given 25 mg/day of sertraline plus two placebo capsules for 14 days. The first 170 participants who continue to meet the DSM-IV-TR criteria for major depression, score e15 on the Hamilton Rating Scale for Depression (HAM-D), report no serious side effects, and take both drugs >90% of days, will undergo a baseline evaluation and then be randomly assigned to receive either 50 mg/day of sertraline plus omega-3 FA or 50 mg/day of sertraline plus placebo for 10 weeks. At baseline and after 10 weeks, participants will complete assessments of depression, 24 hour ambulatory ECG monitoring to measure 24 hour heart rate and heart rate variability, and blood draws to measure procoagulant and proinflammatory markers and blood levels of EPA, DHA, other omega-3 FAs, and the omega-6 FAs. If sertraline plus this omega-3 formulation significantly reduces depression compared to sertraline plus placebo, and if it improves or at least does not worsen other cardiovascular risk markers, this study will provide a strong basis for proposing a multicenter clinical trial of sertraline augmented with omega-3 to determine whether treatment of depression can improve survival in patients with post-ACS depression.

描述（由申请人提供）：抑郁症使冠心病（CHD）患者心脏发病和死亡的风险增加2-4倍。最近的临床试验已经测试了冠心病患者共病性抑郁的标准治疗方法，有些还评估了它们对心脏发病率和死亡率的影响。这些试验大多表明，标准治疗对抑郁症的影响不大，而且在干预组和对照组之间产生的差异相对较小。因此，他们一直无法确定抑郁症的有效治疗是否能改善心脏预后。低饮食摄入和低血浆磷脂或红细胞水平的两种omega-3脂肪酸，二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），与抑郁症和其他心脏风险标志物有关，包括可能介导抑郁症和心脏死亡率之间的关系。小型精神病学试验中越来越多的证据表明，标准抗抑郁药的疗效可以通过同时服用含有至少1克EPA的omega-3 FA配方，EPA与DHA的比例为2至4份（2-4EPA:1DHA）。本研究的目的是确定在冠心病患者重度抑郁时，加用omega-3 FA制剂的抗抑郁药物是否优于单独的抗抑郁药物治疗，并研究其对这些患者其他心脏危险指标的影响。该研究是一项随机、安慰剂对照、双盲临床试验。急性冠脉综合征（ACS）发生2-4个月后符合DSM-IV-TR重度抑郁发作标准的患者，将给予25 mg/天的舍曲林加2粒安慰剂胶囊，持续14天。前170名继续符合DSM-IV-TR重度抑郁症标准，汉密尔顿抑郁量表（HAM-D）得分为e15分，报告无严重副作用，并且服用两种药物的天数为90%的参与者将接受基线评估，然后随机分配接受50毫克/天的舍曲林加omega-3 FA或50毫克/天的舍曲林加安慰剂，为期10周。在基线和10周后，参与者将完成抑郁评估，24小时动态心电图监测以测量24小时心率和心率变异性，并抽血测量促凝剂和促炎标志物以及EPA， DHA，其他omega-3脂肪酸和omega-6脂肪酸的血液水平。如果与舍曲林加安慰剂相比，舍曲林加omega-3制剂能显著减少抑郁，并且能改善或至少不会恶化其他心血管风险指标，那么该研究将为提出舍曲林加omega-3的多中心临床试验提供强有力的基础，以确定抑郁症治疗是否能提高acs后抑郁症患者的生存率。