Treating Depression in Parkinson's Disease: A New Method

描述（由申请人提供）：抑郁症是帕金森病（PD）中最常见的精神障碍，与身体症状的更快进展、更大的认知下降和更差的生活质量有关。尽管未经治疗的抑郁症会加速患者在许多领域的残疾，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）的抑郁症，但结论受到方法学缺陷和耐受性问题的限制。类似地，尽管在其他老年人群中表现出很强的疗效，但用于治疗dPD的非药物方法几乎没有得到实验关注。该K奖的主要目的是评估认知行为治疗包的疗效，其中包括以抑郁症为中心的社会支持干预，用于PD中的抑郁症和其他精神并发症。还将探索4个患者变量（社会支持、执行功能障碍、共病精神病理学和运动波动）对治疗反应的影响（目的2）。为了计划未来的试验（目标3），将检查用于所有目的（抑郁症、PD、其他医学疾病）的药物使用对治疗结果的影响。将本非药物治疗试验的招募、保留和不良事件发生率以及保持盲态的能力与主要导师当前R 01中观察到的相同发生率进行比较，以检查抗抑郁药与安慰剂对dPD的影响（目标3）。共80例PD（无显著运动波动或痴呆）和抑郁症（重度抑郁症、心境恶劣、抑郁症NOS）患者将被随机分配接受标准医疗护理或认知行为治疗包加标准医疗护理。研究计划，加上拟议的培训活动（例如，导师，正式的课程，动手学习经验）将使候选人扩大她的知识基础，1）帕金森病的大脑行为机制，2）帕金森病抑郁症的诊断复杂性，3）运动和非运动症状，以及4）先进的研究设计和统计方法有关的治疗结果研究在PD。这些都是必要的先决条件，她的长期目标-启动一个独立的以病人为导向的研究生涯，重点是非药物管理的精神并发症在PD。拟议的主要导师（马修门扎）和UMDNJ的环境将大大促进候选人的新的初级教师到独立调查员的过渡。这是第一项在随机对照试验中评估认知行为治疗对PD抑郁症的影响的研究。鉴于改善PD抑郁症治疗对公共卫生的影响，所获得的知识可能是重要的，该项目可能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.