Paroxetine/Bupropion in Suicide Attempters/Ideators with Major Depression

描述（由申请人提供）：重度抑郁症（MOD）是一种常见的严重精神疾病。它是导致残疾的主要原因之一，也是最常与自杀有关的精神疾病。然而，用抗抑郁药物治疗MOD在很大程度上仍然是一个试错的过程，当自杀预防是一个优先事项时，几乎没有经验证据可以指导治疗。这个以患者为导向的K奖的目的是开发和执行一项研究计划，该计划将调查MOD和自杀企图史的高风险样本中对不同类型抗抑郁药物反应的临床，神经心理学和遗传预测因素。将比较在使用多巴胺能抗抑郁药与非多巴胺能抗抑郁药治疗期间抑郁症的临床和神经心理学成分以及自杀素质的变化。我们还将确定与抑郁症或自杀素质相关的基因的功能多态性是否预测这些抗抑郁药对自杀素质的情绪或成分的治疗效果。首席研究员将在J. John Mann博士的大力指导下开展这项研究职业发展计划（用于抑郁症和自杀的临床神经生物学培训）。积极的咨询和额外的指导将来自博士。John Rush（抗抑郁药临床试验设计和执行培训）、Dr.布鲁斯G.波洛克（抗抑郁药物遗传学培训），约瑟夫D。Terwilliger（遗传流行病学培训）、John Keilp博士（神经心理学测试使用培训）和伊娃Petkova博士（统计分析方法培训）。这个以患者为导向的职业发展奖将为主要研究者提供进一步的经验和技能，以整合抑郁症和自杀临床试验研究领域的临床和科学专业知识。该奖项的长期目标是使候选人成为治疗抑郁症的专家和独立的临床研究人员，特别关注自杀预防。

DESCRIPTION (provided by applicant): Major depressive disorder (MOD) is a common and serious psychiatric illness. It is among the leading causes of disability and is the psychiatric disorder most frequently associated with suicide. Yet the treatment of MOD with antidepressant medication remains largely a trial-and-error process and little empirical evidence exists to guide treatment when suicide prevention is a priority. The purpose of this patient-oriented K-award is to develop and execute a program of research that will investigate clinical, neuropsychological and genetic predictors of response to different types of antidepressant medications in a high-risk sample of persons with MOD and a history of suicide attempt. Changes in clinical and neuropsychological components of depression and the diathesis for suicide will be compared during treatment with a serotonergic versus a non- serotonergic antidepressant. We will also determine whether functional polymorphisms in genes related to depression or the diathesis for suicide predict therapeutic effects of these antidepressants on mood or components of the diathesis for suicide. The principal investigator will carry out this program of research career development under the strong mentorship of Dr. J. John Mann (for training in the clinical neurobiology of depression and suicide). Active consultation and additional mentorship will come from Dr. A. John Rush (for training in antidepressant clinical trial design and execution), Dr. Bruce G. Pollock (for training in antidepressant pharmacogenetics), Dr. Joseph D. Terwilliger (for training in genetic epidemiology), Dr. John Keilp (for training in use of neuropsychological tests) and from Dr. Eva Petkova (for training in statistical analytic methods). This patient-oriented career development award will provide the principal investigator with the further experience and skills necessary to integrate clinical and scientific expertise in the field of depression and suicide clinical trials research. The long-term goal of this award is for the candidate to become an expert and independent clinical researcher on the treatment of depression with a special focus on suicide prevention.