Improving Psychiatric Interventions at the End of Life

项目概要/摘要： 导言：这是一个继续职业发展计划的建议， 精神病问题和对接近生命尽头的人的干预，特别是重度抑郁症 紊乱诸如临终时的抑郁症等问题给公共卫生带来的负担是巨大的， 不仅是为了病人还有他们的亲人改善精神病护理和干预措施， 每年将改善100多万人的生活，使患者和家庭能够 在他们最后的时光里，与其在痛苦中度过，不如一起度过。现有证据- 基于抑郁症的干预措施对患者来说不够快或不够频繁 只剩下几周的生命小型研究和我们的试点工作为以下方面提供了初步证据： 哌甲酯快速治疗临终关怀中抑郁症的安全性和有效性。一 继续由Dilip Jeste和Charles von Gunten领导的指导团队将指导 从一个成功的基础科学家到一个成功的基础科学家的转变候选人的发展 独立的面向患者的研究者和临床试验者，特别注重进行 在脆弱和患病人群中进行临床试验。总体目标是发展 候选人成为一个独立的科学家谁将获得RO 1资金在一个新的和关键的 重要领域，精神病收容所和姑息治疗。这一建议符合《 国家精神卫生研究所加强在不同地区实施精神卫生干预措施的战略计划 通过检查社区和干预提供方法， 影响干预结果，并可能提供一个知识基础，以移动证据- 将干预措施付诸实践。具体目标：在接受临终关怀的患者中， 当前重度抑郁发作，28天双盲、对照药物对照、灵活剂量 进行哌甲酯与西酞普兰单药治疗的试验，以评估：1） 比较有效性和起效时间，和2）比较安全性和耐受性， 这些药物用于治疗这一人群中的重度抑郁发作。我们假设 哌醋甲酯治疗可以：1）降低抑郁症的严重程度， 症状和2）诱导反应的严重抑郁发作显着快于 西酞普兰方法：一项为期28天的双盲、对照、灵活剂量试验， 哌甲酯单药治疗与西酞普兰单药治疗研究的安全性，耐受性， 在接受临终关怀的患者中治疗重性抑郁症的疗效和起效时间 进行了护理。在前15个月内，剂量滴定至可耐受的作用或副作用。 天患者在研究的剩余时间内保持最终稳定剂量。中指出 虽然本试验是临床试验问题培训的有用工具，但是， 试验本身因招募不足而取消。其他几项研究已经完成 调查氯胺酮用于临终关怀患者抑郁症的快速治疗，以及 临终关怀病人的认知障碍、临终关怀照顾者压力和自杀的研究。 结论：从事临终关怀的精神科医生很少， 是调查员继续资助这项提案将给我剩下的经验 有必要提高认识和治疗临终精神病问题的科学 成为独立调查员有效的治疗方法与以下因素有显著相关性： 患者、他们的亲人和护理人员。在这个奖项下，一些研究已经 完成了对影响临终关怀的各种精神问题的研究，包括两个 调查氯胺酮用于临终关怀患者抑郁症的快速治疗。的 这些调查的结果现在将用于本合同的其余部分， 在严重晚期疾病患者中开展的大规模随机对照试验研究 接受临终关怀（姑息治疗）前护理。

Project Summary / Abstract: Introduction: This is a proposal to continue a career development program for the study of psychiatric issues and interventions for people near the end-of-life, specifically major depressive disorders. The public health burden of issues such as depression at the end-of-life is enormous, not only for the patients, but their loved ones. Improved psychiatric care and interventions in this population would improve the lives of over a million people a year, allowing patients and families to be engaged in their final hours together, rather than to spend them in misery. Current evidence- based interventions for depression do not work fast enough or frequently enough for patients with only weeks to live. Small studies and our pilot work have provided initial evidence for the safety and efficacy of methylphenidate for rapidly treating depression in hospice settings. A mentoring team continuing to be led by Dilip Jeste and Charles von Gunten will guide the development of the candidate in the transformation from a successful basic scientist to an independent patient oriented researcher and clinical trialist, with a special focus on conducting clinical trials in vulnerable and medically-ill populations. The overall goal is to develop the candidate into an independent scientist who would obtain RO1 funding in a new and critically important area, psychiatric hospice and palliative care. This proposal is consistent with the NIMH strategic plan of strengthening the application of mental health interventions in diverse care settings by examining community and intervention delivery approaches , how they may affect intervention outcomes, and potentially providing a knowledge base to move evidence- based interventions into practice. SPECIFIC AIMS: In patients receiving hospice care with a current major depressive episode, a 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate vs. citalopram monotherapy was conducted to assess both: 1) the comparative efficacy and onset of action, and 2) the comparative safety and tolerability of using these medications for treating major depressive episodes in this population. We hypothesized that treatment with methylphenidate would both: 1) Reduce the severity of depressive symptoms and 2) Induce a response of major depressive episodes significantly faster than citalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate monotherapy vs. citalopram monotherapy investigating the safety, tolerability, efficacy, and time to efficacy for the treatment of major depression in patients receiving hospice care was conducted. Doses were titrated to tolerable effects or side-effects in the first fifteen days. Patients remained on the final stable dose for the remainder of the study. As noted in the progress reports, this trial was a useful tool for training about clinical trial issues; however, the trial itself was cancelled due to lack of enrollment. Several other studies have been completed investigating ketamine for the rapid treatment of depression in hospice patients, as well as studies of cognitive impairments, hospice caregiver stress, and suicide in hospice patients. Conclusions: There are very few psychiatrists working in end-of-life care, and even fewer who are investigators. Continued funding of this proposal will give me the rest of the experience necessary to improve the science of recognizing and treating psychiatric issues at the end-of-life and become and independent investigator. Effective treatments have significant relevance for patients, their loved ones, and caregivers. Under this award, several studies have been completed looking at various psychiatric issues affecting those in hospice care, including two investigating the use of ketamine for the rapid treatment of depression in hospice patients. The results of these investigations will now be used for the remainder of this award to design and pilot larger-scale randomized controlled studies of patients with serious advanced illnesses receiving pre-hospice (palliative) care.