CARDIAC RISK MARKERS AND UNREMITTING DEPRESSION IN ACUTE CORONARY SYNDROME

描述（由研究者提供）：抑郁症是急性冠脉综合征（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，治疗难治性抑郁症患者的死亡风险高于那些对抑郁症标准治疗有反应的患者。有趣的是，抑郁症精神病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、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。本研究的目的是验证以下假设：1)积极治疗无效的acs后抑郁患者在治疗结束时的特定心脏危险标志物水平高于有反应的患者；2)治疗前这些心脏危险标志物的高水平预示着抑郁症治疗的不良反应；3)这些风险标记随着治疗应答者抑郁症的改善而改善。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DSM-IV当前重度抑郁发作标准，且在ACS住院约3个月后HAM-D-17评分为17分或更高的患者将被纳入研究。所有参与者将接受个体认知行为疗法（CBT）治疗长达6个月。当达到特定的改善标准时，CBT疗程的频率会减少。3个月后BDI-II抑郁问卷没有改善50%的患者将继续CBT治疗，但也将给予初始剂量为50mg /天的舍曲林。如果有必要和耐受，剂量将逐渐增加到最大200mg /天。将在基线、3个月和6个月时评估抑郁症，并测量心脏风险指标。结构方程模型将用于检验主要假设。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。最初试图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是如何增加死亡风险的，并可能提出开发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。最初试图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是如何增加死亡风险的，并可能提出开发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.