Treating Depression in Parkinson's Disease: A New Method

描述(申请人提供)：抑郁症是帕金森氏病(PD)中最常见的精神障碍，与身体症状进展更快、认知能力下降和生活质量下降有关。尽管未经治疗的抑郁症会在许多领域加速患者的残疾，但目前还没有基于证据的护理标准。虽然一些安慰剂对照试验支持使用抗抑郁药治疗帕金森病(DPD)，但结论受到方法学缺陷和耐受性问题的限制。同样，尽管在其他老年人群中显示出了很强的疗效，但非药物治疗DPD的方法几乎没有受到实验的关注。K奖的主要目的是评估认知-行为治疗方案的有效性，其中包括以照顾者为中心的社会支持干预，以治疗帕金森病患者的抑郁和其他精神并发症。还将探讨四个患者变量(社会支持、执行功能障碍、共病精神病和运动波动)对治疗反应的影响(目标2)。为了计划未来的试验(目标3)，将检查所有目的(抑郁症、帕金森病、其他医疗条件)的药物使用对治疗结果的影响。这项非药物治疗试验的招募、保留率和不良事件发生率以及保持盲人的能力将与初级导师当前R01中观察到的相同比率进行比较，以检查抗抑郁药与安慰剂对DPD的影响(目标3)。共有80名帕金森病患者(没有明显的运动波动或痴呆)和抑郁症(重度抑郁、心境恶劣、抑郁-一氧化氮合酶)患者将被随机分配到接受标准医疗或认知行为治疗包加标准医疗护理。研究计划，加上建议的培训活动(例如，导师指导、正式课程作业、实践学习经验)将使应聘者能够扩大她的知识基础，涉及1)帕金森氏症的大脑行为机制，2)帕金森氏症抑郁的诊断复杂性，3)运动和非运动症状，以及4)与帕金森病治疗结果研究相关的高级研究设计和统计方法。这些都是她实现长期目标的必要先决条件--启动一项独立的、以患者为导向的研究事业，专注于帕金森病精神并发症的非药物管理。建议的主要导师(马修·门扎)和UMDNJ的环境将极大地促进候选人从初级教员向独立调查员的转变。这是第一项在随机对照试验中评估认知行为疗法对帕金森病抑郁影响的研究。鉴于改进的抑郁症治疗对公众健康的影响，将获得的知识可能是重要的，该项目可能会对临床实践产生直接影响。

DESCRIPTION (provided by applicant): Depression, the most common psychiatric disturbance in Parkinson's disease (PD), is linked with a faster progression of physical symptoms, greater cognitive decline, and poorer quality of life. Despite the fact that untreated depression accelerates the patients' disability in numerous domains, there is currently no evidence-based standard of care. While some placebo-controlled trials have supported the use of antidepressants for depression in Parkinson's disease (dPD), conclusions have been restricted by methodological shortcomings and tolerability concerns. Similarly, non-pharmacological approaches for the treatment of dPD have received little experimental attention despite strong demonstrated efficacy in other geriatric populations. The primary aim of this K-Award is to evaluate the efficacy of a cognitive-behavioral treatment package, that includes a caregiver-focused social support intervention, for depression and other psychiatric complications in PD. The impact of four patient variables (social support, executive dysfunction, comorbid psychopathology, and motor fluctuations) on treatment response will also be explored (Aim 2). In order to plan for a future trial (Aim 3), the effect of medication use for all purposes (depression, PD, other medical conditions) on treatment outcome will be examined. The recruitment, retention and adverse event rates, and the ability to maintain the blind for this non-pharmacological treatment trial will be compared to those same rates observed in the primary mentor's current R01 examining the impact of antidepressants versus placebo on dPD (Aim 3). A total of 80 patients with PD (without significant motor fluctuations or dementia) and depression (major depression, dysthymia, depression NOS) will be randomly assigned to receive either standard medical care or the cognitive-behavioral treatment package plus standard medical care. The research plan, coupled with the training activities proposed (e.g., mentorship, formal coursework, hands-on learning experiences) will enable the candidate to broaden her knowledge base regarding 1) the brain-behavior mechanisms in PD, 2) the diagnostic complexities of PD depression, 3) the motor and non-motor symptoms, and 4) advanced research design and statistical methods pertinent to treatment outcome research in PD. These are necessary prerequisites to her long term goal- the launching of an independent patient-oriented research career focused on the non-pharmacological management of the psychiatric complications in PD. The proposed primary mentor (Matthew Menza) and the UMDNJ environment will greatly facilitate the candidate's transition from new junior faculty member to independent investigator. This is the first study to evaluate the impact of a cognitive-behavioral treatment for PD depression in a randomized controlled trial. Given the public health impact of improved depression treatment in PD, the knowledge to be gained may be significant and the project could have a direct impact on clinical practice.