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，与身体症状进展更快、认知能力下降更大、生活质量更差有关。尽管未经治疗的抑郁症会加速患者在许多方面的残疾，但目前还没有循证的护理标准。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）抑郁症，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表现出了很强的疗效，但治疗dPD的非药物方法却很少得到实验关注。这个k奖的主要目的是评估认知行为治疗包的疗效，包括以护理者为中心的社会支持干预，治疗PD患者的抑郁症和其他精神并发症。还将探讨四个患者变量（社会支持、执行功能障碍、共病精神病理和运动波动）对治疗反应的影响（目的2）。为了计划未来的试验（目标3），将检查所有目的（抑郁症、PD、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率、保留率和不良事件发生率以及保持盲性的能力将与主要导师当前R01中观察到的相同比率进行比较，R01检查抗抑郁药与安慰剂对dPD的影响（目的3）。共有80名PD（无明显运动波动或痴呆）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。该研究计划，加上提出的培训活动（如指导，正式课程，实践学习经验），将使候选人拓宽她的知识基础，1)PD的大脑行为机制，2)PD抑郁症的诊断复杂性，3)运动和非运动症状，4)与PD治疗结果研究相关的先进研究设计和统计方法。这些都是她长期目标的必要先决条件——启动一个独立的以患者为导向的研究事业，专注于PD中精神并发症的非药物管理。提议的主要导师（Matthew Menza）和UMDNJ的环境将极大地促进候选人从新的初级教员到独立研究者的过渡。这是第一项在随机对照试验中评估认知行为治疗PD抑郁症影响的研究。鉴于PD患者改善抑郁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.