CARDIAC RISK MARKERS AND UNREMITTING DEPRESSION IN ACUTE CORONARY SYNDROME

描述(由研究人员提供)：抑郁是急性冠脉综合征(ACS)住院后死亡的危险因素。然而，最近几项临床试验的综合证据表明，与那些接受标准治疗的抑郁症患者相比，难治性抑郁症患者的死亡风险更高。有趣的是，抑郁症患者治疗抵抗的一些最强预测因子碰巧也是心脏风险标记物，包括心血管自主神经失调、HPA轴失调以及促炎和促凝血过程的指标。此外，这些标记物也被认为是抑郁对急性冠脉综合征后死亡率影响的潜在中介。这项研究的目的是验证以下假设：1)对积极的抑郁症治疗无效的急性冠脉综合征后抑郁患者在治疗结束时比其他有反应的可比患者具有更高的特定心脏风险标记物水平；2)治疗前这些心脏风险标记物的高水平预示着对抑郁症治疗的不良反应；以及3)这些风险标记物随着治疗应答者中抑郁的改善而改善。参与者将从华盛顿大学医学院附属的三家圣路易斯地区医院招募。170名符合当前严重抑郁发作的DSM-IV标准，并且在入院治疗ACS约3个月后HAM-D-17得分17或更高的患者将参加这项研究。所有参与者都将接受为期长达6个月的个人认知行为治疗(CBT)。当满足具体的改进标准时，CBT会议的频率将会降低。在BDI-II抑郁问卷调查中3个月仍未改善50%的患者将继续接受CBT治疗，但也将接受舍曲林的初始剂量为50毫克/天。如有需要和耐受性，剂量会逐步增加至每天最多200毫克。将评估抑郁，并在基线、3个月和6个月时测量心脏风险标记物。结构方程模型将被用来检验主要假设。相关性：抑郁症使心脏病发作后死亡的风险增加一倍，原因尚不清楚。最初通过治疗抑郁症来降低这种风险的努力并不成功。这项研究将有助于阐明抑郁症如何增加死亡风险，并可能为开发更有效的干预措施提供建议。与公共卫生相关：抑郁症使心脏病发作后死亡的风险增加一倍，原因尚不清楚。最初通过治疗抑郁症来降低这种风险的努力并不成功。这项研究将有助于阐明抑郁症如何增加死亡风险，并可能为开发更有效的干预措施提供建议。

DESCRIPTION (provided by investigator): Depression is a risk factor for mortality after hospitalization for acute coronary syndrome (ACS). However, converging evidence from several recent clinical trials suggests that the mortality risk is higher among patients with treatment-resistant depression than those who respond to standard treatments for depression. Interestingly, some of the strongest predictors of treatment resistance in depressed psychiatric patients also happen to be cardiac risk markers, including indicators of cardiovascular autonomic dysregulation, HPA axis dysregulation, and proinflammatory and procoagulant processes. Furthermore, these markers have also been identified as potential mediators of the effect of depression on post-ACS mortality. The purpose of this study is to test the hypotheses that 1) depressed post-ACS patients who fail to respond to aggressive treatment for depression have higher levels of specific cardiac risk markers at the end of treatment than do otherwise comparable patients who do respond; 2) high levels of these cardiac risk markers prior to treatment predict poor response to depression treatment; and 3) these risk markers improve as depression improves in treatment responders. Participants will be recruited from three St. Louis area hospitals affiliated with Washington University School of Medicine. One hundred seventy patients, who meet the DSM-IV criteria for a current major depressive episode and who score 17 or higher on the HAM-D-17 approximately 3 months after hospitalization for ACS, will be enrolled in the study. All participants will be treated with individual cognitive behavior therapy (CBT) for up to 6 months. The frequency of CBT sessions will decrease when specific improvement criteria are met. Patients who have not improved >50 percent on the BDI-II depression questionnaire by 3 months will continue in CBT but will also be given sertraline at an initial dosage of 50 mg/day. If necessary and if tolerated, the dosage will be gradually increased to a maximum of 200 mg/day. Depression will be assessed, and cardiac risk markers will be measured, at baseline, 3 months, and 6 months. Structural equation models will be used to test the primary hypotheses. Relevance: Depression doubles the risk of death after a heart attack, for reasons that are not well understood. Initial efforts to reduce this risk by treating depression have not been successful. This study will help to clarify how depression increases the risk of dying, and it may suggest ways to develop more effective interventions. PUBLIC HEALTH RELEVANCE: Depression doubles the risk of death after a heart attack, for reasons that are not well understood. Initial efforts to reduce this risk by treating depression have not been successful. This study will help to clarify how depression increases the risk of dying, and it may suggest ways to develop more effective interventions.