Improving Psychiatric Interventions at the End of Life

描述（由申请人提供）：这是一份职业发展计划的提案，准备研究精神病学问题和接近生命末期的人的干预措施，特别是重度抑郁症。诸如临终抑郁等问题给公共卫生带来的负担是巨大的，不仅对病人，对他们的亲人也是如此。改善对这一人群的精神护理和干预，每年将改善100多万人的生活，使患者和家属能够共同度过最后的时光，而不是在痛苦中度过。目前针对抑郁症的循证干预措施，对生命仅剩几周的患者来说，见效不够快，也不够频繁。小型研究和我们的试点已经为哌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提供了初步证据。一个由博士领导的指导团队。Dilip Jeste和Charles von Gunten将指导候选人从成功的基础科学家转变为以患者为导向的研究人员和临床试验学家，特别注重在弱势和疾病人群中进行临床试验。总体目标是将候选人培养成一名独立的科学家，他将在一个新的、至关重要的领域——精神病学临终关怀——获得R01资助。该建议与NIMH的战略计划一致，即通过检查社区和干预提供方法，以及它们如何影响干预结果，加强在不同护理环境中应用精神卫生干预措施，并可能为将循证干预措施付诸实践提供知识基础。特定目的：在目前患有重度抑郁发作的接受临终护理的患者中，将进行一项为期28天的双盲、比较对照、灵活剂量的哌醋甲酯与艾司西酞普兰单药治疗的试验，以评估：1)在该人群中使用这些药物治疗重度抑郁发作的比较疗效和起效，以及2)比较安全性和耐受性。我们假设，用哌醋甲酯治疗将：1)降低抑郁症状的严重程度，2)诱导重性抑郁发作的反应明显快于艾司西酞普兰。方法：进行为期28天的双盲、比较对照、灵活剂量试验，研究哌醋甲酯单药与艾司西酞普兰单药治疗安宁疗护患者重度抑郁症的安全性、耐受性、有效性和起效时间。剂量将在前15天内调整到可耐受的效果或副作用。在剩余的研究中，患者将继续使用最终稳定剂量。结论：从事临终关怀工作的精神科医生很少，从事调查的就更少了。资助这项提案将使我获得必要的经验，以提高识别和治疗生命末期精神问题的科学水平。有效的治疗对病人、他们的亲人和照顾者都有重要的意义。如果该试验的结果有利于使用哌甲酯，研究结果将用于设计更大的、随机的、多地点的和对照试验。该结果也可用于设计接受临终关怀前护理的患者和/或所有三种人群的护理人员的研究。

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. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to train me to become a clinical trialist and improve upon current psychopharmacological treatments for depression in patients receiving hospice care. Depression in patients receiving hospice care is highly prevalent, and the current evidence-based interventions for depression do not work fast enough or frequently enough for patients with only weeks to live. This study proposes a 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate vs. escitalopram monotherapy to assess: 1) the comparative efficacy and onset of action of methylphenidate vs. escitalopram for treating major depressive episodes, and 2) the comparative safety and tolerability of using methylphenidate vs. escitalopram in patients receiving hospice care.