Improving Psychiatric Interventions at the End of Life

描述(由申请人提供)：这是一个职业发展计划的建议，准备研究精神问题和对临终患者的干预，特别是严重的抑郁障碍。临终抑郁等问题给公共卫生带来的负担是巨大的，不仅对患者，对他们的亲人也是如此。改善这一人群的精神护理和干预措施每年将改善100多万人的生活，使患者和家人能够在最后几个小时共度时光，而不是在痛苦中度过。目前对抑郁症的循证干预效果不够快，也不够频繁，对只有几周生命的患者来说。小型研究和我们的试点已经提供了初步证据，表明哌醋甲酯在临终关怀环境中快速治疗抑郁症的安全性和有效性。由Dilip Just博士和Charles von Gunten博士领导的指导团队将指导候选人从一名成功的基础科学家转变为以患者为中心的研究人员和临床试验人员，特别关注在脆弱和患有内科疾病的人群中进行临床试验。总体目标是将候选人发展成为一名独立的科学家，他将在一个新的和至关重要的领域--精神临终关怀--获得R01资金。这一建议符合NIMH的战略计划，即通过检查社区和干预交付方法，它们可能如何影响干预结果，并潜在地提供一个知识库，将循证干预付诸实践，从而加强精神健康干预在不同护理环境中的应用。具体目标：在接受临终关怀、目前有严重抑郁发作的患者中，将进行为期28天的双盲、对照控制、灵活剂量的哌醋甲酯与艾司匹兰单一疗法试验，以评估两种药物的比较有效性和起效时间，以及2)在这一人群中使用这些药物治疗严重抑郁发作的相对安全性和耐受性。我们假设，使用哌醋甲酯治疗将：1)减轻抑郁症状的严重程度，2)显著快于艾司西普兰对主要抑郁发作的反应。方法：对接受临终关怀的重度抑郁症患者进行为期28天的双盲、对照对照、灵活剂量试验，观察其安全性、耐受性、疗效和起效时间。剂量将在最初的15天内滴定到可耐受的效果或副作用。在剩下的研究中，患者将继续服用最后稳定的剂量。结论：从事临终关怀的精神病学家寥寥无几，研究人员更是寥寥无几。资助这项提案将给我必要的经验，以提高在生命末期识别和治疗精神问题的科学。有效的治疗与患者、他们的亲人和照顾者密切相关。如果这项试验的结果有利于使用哌醋甲酯，研究结果将被用于设计更大规模的、随机的、多地点的对照试验。该结果也可用于设计对接受临终关怀前护理的患者和/或所有三个人群的照顾者的研究。

DESCRIPTION (provided by applicant): This is a proposal for a career development program preparing for 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 also 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 have provided initial evidence for the safety and efficacy of methylphenidate for rapidly treating depression in hospice settings. A mentoring team led by Drs. Dilip Jeste and Charles von Gunten will guide the development of the Candidate in the transformation from a successful basic scientist to a 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 R01 funding in a new and critically important area, psychiatric hospice 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. escitalopram monotherapy will be 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 hypothesize that treatment with methylphenidate will both: 1) Reduce the severity of depressive symptoms and 2) Induce a response of major depressive episodes significantly faster than escitalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate monotherapy vs. escitalopram monotherapy investigating the safety, tolerability, efficacy, and time to efficacy for the treatment of major depression in patients receiving hospice care will be conducted. Dose will be titrated to tolerable effects or side-effects in the first fifteen days. Patients will remain on the final stable dose for the remainder of the study. Conclusions: There are very few psychiatrists working in end-of-life care, and even fewer who are investigators. Funding this proposal will give me the experience necessary to improve the science of recognizing and treating psychiatric issues at the end-of-life. Effective treatments have significant relevance for patients, their loved ones, and caregivers. Should the results of this trial favor use of methylphenidate, the findings will be used to design larger, randomized, multi-site, and controlled trials. The results may also be used to design studies of patients receiving pre-hospice care and/or of caregivers of all three populations.