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

项目总结/摘要 这项补助金，题为“预防复发和双相抑郁症复发”，是一个链接的2个网站，研究者- 根据NIMH PA-07-092提交的启动试验。该补助金的主题是双相I型（BP I）重大复发 抑郁发作（MDE），现在被认为是一个主要的心理健康问题。复发性BP I MDE是一种 目前尚无令人满意的治疗方法，其治疗仍是临床医生面临的挑战。迄今为止， BPIMDE的长期治疗基于未经验证的实践指南。这些准则 建议在BP I MDE的初始治疗期间限制抗抑郁药（AD）的使用，并完全避免 长期治疗期间使用AD。然而，没有经验证据表明情绪稳定剂 (MS)单药治疗在预防复发性BP I MDE方面上级MS + AD联合治疗。也没有 有证据表明，长期MS加AD治疗会导致更多的躁狂转换发作。我们提出 有证据表明，BP I MDE长期治疗期间AD诱导的躁狂被高估， 长期使用MS加AD治疗在预防复发性BP I MDE方面可能上级单独使用MS治疗。 在这个建议中，我们会问：“联合锂+氟西汀的持续治疗是否会减少 MDE复发和再发vs锂单药治疗？“要回答这个问题，BP I MDE患者将 给予锂剂联合氟西汀治疗8周。在另外4天内保持良好的应答者 然后将巩固治疗10周的患者随机分配至双盲持续治疗组，其中（i） 联合锂加氟西汀，或（ii）单独锂（在氟西汀逐渐减少和停药后）， 额外50周。我们假设长期锂盐联合氟西汀治疗将导致更少的MDE 复发和复发与锂单药治疗。我们还将问：“什么是相对安全性，耐受性， 以及在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频率 锂盐联合氟西汀与锂盐单药治疗的持续治疗？“为了回答这个问题， 问题，我们将测量：频率，严重程度和持续时间的综合征和亚综合征躁狂， 轻躁狂和混合状态转换;治疗后出现的不良反应的频率、严重程度和持续时间 事件;停药频率;至首次发生综合征和亚综合征转换的时间 事件;至各综合征和亚综合征转换事件首次治疗干预的时间;以及至 自杀意念事件开始增加。我们假设锂盐加氟西汀治疗会导致 相似的综合征和亚综合征转换事件频率，以及相似的治疗频率- 紧急不良事件。我们进一步假设，锂加氟西汀治疗将导致更少的自杀 与锂单药治疗相比，构思事件和更少的研究中止。我们认为，这一结果 这项试验可能对目前治疗BP I MDE的实践指南产生重要的公共卫生影响。

Project Summary/Abstract This grant, entitled "Prevention of Relapse & Recurrence of Bipolar Depression," is a linked 2-site, investigator- initiated trial submitted under NIMH PA-07-092. 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 proposal, 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.