1/2-Prevention of Relapse & Recurrence of Bipolar Depression

1/2-预防复发

• 批准号: 7643557
• 负责人: JAY D AMSTERDAM
• 金额: $ 39.75万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643557
• 关键词: Acute; Adult; Adverse event; Affect; Affective; Alcoholism; Antidepressive Agents; Arts; Attention; Benefits and Risks; Bipolar Depression; Bupropion; Clinical; Consensus; Consolidation Therapy; Data; Disease; Double-Blind Method; Drug usage; Epidemiologic Studies; Event; Feeling suicidal; Fluoxetine; Frequencies; Future; Grant; Guidelines; Hamilton Rating Scale for Depression; Health Care Costs; Intervention; Intervention Trial; Link; Lithium; Manic; Measures; Mental Health; Mental disorders; Mood stabilizers; Moods; Morbidity - disease rate; National Institute of Mental Health; Outcome Measure; Patient Recruitments; Patients; Pharmacotherapy; Phase; Population; Practice Guidelines; Prevention; Principal Investigator; Protocols documentation; Psychopathology; Public Health; Quality Control; Randomized; Randomized Controlled Clinical Trials; Recovery; Recurrence; Rehabilitation therapy; Relapse; Relative (related person); Reporting; Research; Safety; Sample Size; Selective Serotonin Reuptake Inhibitor; Severities; Site; Substance abuse problem; Symptoms; Time; Work; base; control trial; data management; depressed; depressive symptoms; discontinuation trial; disorder later incidence prevention; drug efficacy; functional outcomes; prevent; public health relevance; single episode major depressive disorder; suicidal risk; therapy outcome; treatment duration

DESCRIPTION (provided by applicant): The subject of this grant, recurrence of Bipolar I (BP I) major depressive episode (MDE), is now recognized as a major mental health problem. Recurrent BP I MDE is a disorder with no satisfactory therapy, and its treatment remains a challenge to clinicians. To date, initial and long-term therapy of BP I MDE has been based on un-validated practice guidelines. These guidelines recommend limiting antidepressant drug (AD) use during initial therapy of BP I MDE, and completely avoiding AD use during long-term therapy. There is, however, no empirical evidence to suggest that mood stabilizer (MS) monotherapy is superior to combined MS plus AD therapy in preventing recurrent BP I MDE. Nor is there evidence to suggest that long-term MS plus AD therapy results in more manic switch episodes. We present evidence that AD-induced mania during long-term therapy of BP I MDE has been over-estimated, and that long-term use of MS plus AD therapy may be superior to MS therapy alone in preventing recurrent BP I MDE. In this application, we will ask: "Does continuation therapy with combined lithium plus fluoxetine result in fewer MDE relapses and recurrences vs. lithium monotherapy?" To answer this question, patients with BP I MDE will receive combined lithium plus fluoxetine therapy for 8 weeks. Responders who stay well for an additional 4 weeks of consolidation therapy will then be randomized to double-blind continuation therapy with either (i) combined lithium plus fluoxetine, or (ii) lithium alone (following fluoxetine taper and discontinuation) for an additional 50 weeks. We hypothesize that long-term lithium plus fluoxetine therapy will result in fewer MDE relapses and recurrences vs. lithium monotherapy. We will also ask: "What is the relative safety, tolerability, and frequency of syndromal and sub-syndromal manic, hypomanic, and mixed state conversions during continuation treatment with combined lithium plus fluoxetine vs. lithium monotherapy?" To answer this question, we will measure: the frequency, severity, and duration of syndromal and sub-syndromal manic, hypomanic, and mixed state conversions; frequency, severity, and duration of treatment-emergent adverse events; frequency of treatment discontinuation; time to onset of first syndromal and sub-syndromal conversion event; time to first treatment intervention of each syndromal and sub-syndromal conversion event; and, time to onset of increase in suicidal ideation event. We hypothesize that lithium plus fluoxetine therapy will result in a similar frequency of syndromal and sub-syndromal conversion events, and a similar frequency of treatment- emergent adverse events. We further hypothesize that lithium plus fluoxetine therapy will result in fewer suicide ideation events and fewer study discontinuations vs. lithium monotherapy. We believe that the results of this trial may have an important public health impact on the current practice guidelines for treating BP I MDE. PUBLIC HEALTH RELEVANCE: This application comports with the public health intent of PA-07-092 which seeks to "support collaborative intervention trials in the treatment, prevention, or rehabilitation of those with mental disorders." This is a linked collaborative grant mechanism that allows for the use of a common protocol among two or more sites in order to increase sample size and accelerate patient recruitment. The principal investigators of the sites have an established "mechanism for cross-site coordination, quality control, data management, statistical analysis, and reporting." This grant employs state-of-the-art clinical therapy and outcome measures to identify the best long- term therapy of Bipolar I (BP I) major depressive episode (MDE). Results from this study may provide new information on the prevention of relapse and recurrence of BP I MDE, and may have an important public health impact on current practice guidelines for BP I MDE. Results from this study may also inform new research hypotheses for future trials in BP I disorder.

描述（由申请人提供）：本次资助的主题是 I 型双相情感障碍 (BPI) 重度抑郁发作 (MDE) 的复发，现已被认为是一个主要的心理健康问题。复发性BP I MDE是一种尚无令人满意的治疗方法的疾病，其治疗仍然是临床医生面临的挑战。迄今为止，BP I MDE 的初始和长期治疗都是基于未经验证的实践指南。这些指南建议在 BP I MDE 初始治疗期间限制抗抑郁药物 (AD) 的使用，并在长期治疗期间完全避免使用 AD。然而，没有经验证据表明情绪稳定剂 (MS) 单一疗法在预防复发性 BP I MDE 方面优于 MS 加 AD 联合疗法。也没有证据表明长期 MS 加 AD 治疗会导致更多的躁狂发作。我们提供的证据表明，长期治疗 BP I MDE 期间 AD 诱发的躁狂被高估了，并且长期使用 MS 加 AD 治疗在预防复发性 BP I MDE 方面可能优于单独使用 MS 治疗。在此应用中，我们会问：“与锂单药治疗相比，联合锂加氟西汀的持续治疗是否会导致更少的 MDE 复发和复发？”为了回答这个问题，BP I MDE 患者将接受为期 8 周的锂加氟西汀联合治疗。在额外 4 周的巩固治疗中保持良好状态的应答者将被随机分配至双盲继续治疗组，即 (i) 锂加氟西汀联合治疗，或 (ii) 单用锂（在氟西汀逐渐减量并停药后），再持续 50 周。我们假设，与锂单药治疗相比，长期锂加氟西汀治疗将导致更少的 MDE 复发和复发。我们还将问：“与锂单药治疗相比，在继续锂加氟西汀联合治疗期间，综合征和亚综合征躁狂、轻躁狂和混合状态转换的相对安全性、耐受性和频率是多少？”为了回答这个问题，我们将测量： 综合征和亚综合征躁狂、轻躁狂和混合状态转换的频率、严重程度和持续时间；治疗中出现的不良事件的频率、严重程度和持续时间；停止治疗的频率；首次综合征和亚综合征转换事件发生的时间；每个综合征和亚综合征转化事件的首次治疗干预时间；并且，自杀意念事件增加的发生时间。我们假设锂加氟西汀治疗将导致相似的综合征和亚综合征转化事件频率，以及相似的治疗中出现的不良事件频率。我们进一步假设，与锂单药治疗相比，锂加氟西汀治疗将导致更少的自杀意念事件和更少的研究中止。我们相信，这项试验的结果可能对当前治疗 BP I MDE 的实践指南产生重要的公共卫生影响。 公共卫生相关性：本申请符合 PA-07-092 的公共卫生意图，旨在“支持精神障碍患者治疗、预防或康复方面的协作干预试验”。这是一种链接的协作资助机制，允许在两个或多个站点之间使用通用协议，以增加样本量并加速患者招募。这些站点的主要研究人员建立了“跨站点协调、质量控制、数据管理、统计分析和报告机制”。该赠款采用最先进的临床治疗和结果测量来确定双相情感障碍 I (BPI) 重度抑郁发作 (MDE) 的最佳长期治疗。这项研究的结果可能提供有关预防 BP I MDE 复发和复发的新信息，并可能对 BP I MDE 的现行实践指南产生重要的公共卫生影响。这项研究的结果也可能为未来 BP I 障碍试验的新研究假设提供信息。