OMEGA-3 FOR DEPRESSION AND OTHER CARDIAC RISK FACTORS

描述(由申请人提供)：抑郁症使冠心病(CHD)患者的心脏病发病率和死亡率增加2-4倍。最近的临床试验测试了冠心病患者并发抑郁的标准治疗方法，一些试验评估了它们对心脏发病率和死亡率的影响。这些试验中的大多数都表明，标准治疗对抑郁症只有轻微的影响，并且在干预和控制条件下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可以改善心脏结果。低饮食摄入量和低血浆磷脂或红细胞中两种omega-3脂肪酸的水平，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记物有关，包括那些可能介导抑郁症和心脏死亡率之间关系的标记物。来自小型精神病学试验的越来越多的证据表明，通过共同使用包含至少1克EPA的omega-3 FA配方，可以提高标准抗抑郁药的疗效，其中EPA与DHA的比例在2-4份之间(2-4EPA：1DHA)。这项拟议的研究的目的是确定在冠心病患者中，加用这种omega-3 FA制剂的抗抑郁药是否优于单用抗抑郁药治疗，并调查其对这些患者的其他心脏危险标志物的影响。这项拟议的研究是一项随机、安慰剂对照、双盲临床试验。急性冠脉综合征(ACS)后2-4个月，符合DSM-IV-TR标准的严重抑郁发作的患者将服用舍曲林25毫克/天，外加两粒安慰剂胶囊，疗程14天。前170名参与者将接受基线评估，然后随机分配，接受舍曲林50毫克/天加omega-3脂肪酸或舍曲林50毫克/天加安慰剂的治疗。这些参与者在汉密尔顿抑郁量表(HAM-D)上的得分为e15，无严重副作用，服用两种药物的天数均为90%。在基线和10周后，参与者将完成抑郁评估，24小时动态心电监测以测量24小时心率和心率变异性，并抽血测量促凝血和促炎标记物以及血液中EPA、DHA、其他omega-3脂肪酸和omega-6 FA的水平。如果舍曲林加这种omega-3制剂与舍曲林加安慰剂相比能显著降低抑郁症，如果它改善或至少不会恶化其他心血管风险指标，这项研究将为提出一项含omega-3舍曲林的多中心临床试验提供强有力的基础，以确定抑郁症的治疗是否能提高急性冠脉综合征后抑郁症患者的存活率。

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.