CARDIAC RISK MARKERS AND UNREMITTING DEPRESSION IN ACUTE CORONARY SYNDROME

描述（由研究者提供）：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证据表明，难治性抑郁症患者的死亡风险高于对抑郁症标准治疗有反应的患者。有趣的是，抑郁症患者治疗抵抗的一些最强预测因子也恰好是心脏风险标志物，包括心血管自主神经失调，HPA轴失调以及促炎和促凝过程的指标。此外，这些标志物也被确定为抑郁症对ACS后死亡率影响的潜在介质。本研究的目的是检验以下假设：1）对积极治疗抑郁症无效的ACS后抑郁患者在治疗结束时的特定心脏风险标志物水平高于其他有反应的可比患者; 2）治疗前这些心脏风险标志物水平高预示着对抑郁症治疗的反应不良;以及3）这些风险标记随着治疗应答者的抑郁改善而改善。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例符合DSM-IV当前重度抑郁发作标准且因ACS住院后约3个月HAM-D-17评分≥ 17的患者将入组本研究。所有参与者将接受长达6个月的个体认知行为疗法（CBT）治疗。当达到特定的改善标准时，CBT会议的频率将降低。3个月内BDI-II抑郁问卷改善不超过50%的患者将继续接受CBT治疗，但也将给予舍曲林，初始剂量为50 mg/天。如有必要且耐受，剂量将逐渐增加至最大200 mg/天。将在基线、3个月和6个月时评估抑郁症，并测量心脏风险标志物。将使用结构方程模型检验主要假设。相关性：抑郁症使心脏病发作后的死亡风险增加一倍，原因尚不清楚。通过治疗抑郁症来降低这种风险的初步努力并不成功。这项研究将有助于阐明抑郁症如何增加死亡风险，并可能提出制定更有效干预措施的方法。公共卫生相关性：抑郁症使心脏病发作后的死亡风险增加一倍，原因尚不清楚。通过治疗抑郁症来降低这种风险的初步努力并不成功。这项研究将有助于阐明抑郁症如何增加死亡风险，并可能提出制定更有效干预措施的方法。

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.