Treatment of Bipolar Type II Major Depression

描述(由申请人提供)：这项名为“治疗双相II型严重抑郁”的申请是一项竞争性的延续资助，其基础是我们先前由NIMH资助的题为“复发-预防双相II型障碍”的研究(R01MH060353)。这项提案的主题是双相II型(BP II)严重抑郁发作(MDE)，影响2.5%的美国成年人，每年导致估计400亿美元的医疗费用。BP II障碍是一种不同于BP I障碍的独特临床实体，其特点是以MDE为主，导致特别高的发病率和死亡率。BP II MDE的治疗仍然是临床医生面临的挑战。由于担心抗抑郁药物(AD)引起的躁狂发作，目前的实践指南建议使用情绪稳定剂(MS)单一疗法治疗BP II MDE，避免AD单一疗法。到目前为止，还没有对照临床试验来测试这些经验性指南的有效性。我们对BP II MDE的初步研究结果表明，氟西汀或文拉法辛单一治疗BP II MDE可能是一种安全有效的初始治疗方案，躁狂转换率较低。基于这些观察，我们现在问(具体目标#1)：“BP II MDE的初始AD单一疗法与MS单一疗法的相对安全性和有效性如何？”和“BP II MDE的初始AD和MS单一治疗的相对躁狂率是多少？”为了回答这些问题，患有BP II MDE的患者将接受为期12周的随机平行组比较，即文拉法辛单一疗法与锂单一疗法。我们假设AD单一治疗将比MS单一治疗有更好的疗效，并且在两种治疗条件下会有相似的躁狂转换率。我们还会问(具体目标2)：“在已经从MDE中恢复的BP II患者中，持续的AD治疗与MS单一治疗相比有什么疗效？”“在恢复的BP II MDE患者中，持续6个月的AD与MS单一治疗相比，躁狂转换率是多少？”为了回答这个问题，在最初治疗期间有反应的患者将接受文拉法新与锂单一疗法的6个月持续治疗。我们假设AD单一治疗将比MS单一治疗有更好的疗效，并且在两种治疗条件下会有相似的躁狂转换率。如果我们的假设是正确的，我们认为这些结果可能会对目前治疗BP II MDE的实践指南产生重要的公共卫生影响。

DESCRIPTION (provided by applicant): This application, entitled "Treatment of Bipolar Type II Major Depression," is a competing continuation grant that is predicated upon findings from our prior NIMH-funded study entitled "Relapse-Prevention of Bipolar Type II Disorder" (R01 MH060353). Bipolar type II (BP II) major depressive episode (MDE), the subject of this proposal, affects 2.5% of the US adult population and results in an estimated healthcare cost of $40 billion annually. BP II disorder is a distinct clinical entity that differs from BP I disorder, and is characterized by a preponderance of MDEs that result in particularly high morbidity and mortality rates. The treatment of BP II MDE remains a challenge for clinicians. Concerns over antidepressant drug (AD) induced manic switch episodes have led current practice guidelines to recommend treating BP II MDE with mood stabilizer (MS) monotherapy and to avoid AD monotherapy. To date, there are no controlled clinical trials to test the validity of these empirical guidelines. Results from our preliminary BP II MDE studies have shown that fluoxetine or venlafaxine monotherapy may be a safe and effective initial treatment of BP II MDE with a low manic switch rate. Based upon these observations, we now ask (Specific aim #1): "What is the relative safety and efficacy of initial AD monotherapy vs. MS monotherapy of BP II MDE?" and "What is the relative manic switch rate of initial AD vs. MS monotherapy ofBP II MDE?" To answer these questions, patients with BP II MDE will be treated in a 12-week, randomized, parallel group comparison of venlafaxine monotherapy vs. lithium monotherapy. We hypothesize that AD monotherapy will have superior efficacy vs. MS monotherapy, and that there will be a similar manic switch rate among both treatment conditions. We will also ask (Specific Aim #2): "What is the efficacy of continuation AD vs. MS monotherapy in BP II patients who have recovered from their MDE?" and "What is the manic switch rate during continuation AD vs. MS monotherapy for 6 months in recovered BP II MDE patients?" To answer this question, patients who have responded during initial therapy will receive 6-month continuation treatment of venlafaxine vs. lithium monotherapy. We hypothesize that AD monotherapy will have superior efficacy vs. MS monotherapy, and that there will be a similar manic switch rate among both treatment conditions. If our hypotheses are correct, we believe that these results may have an important public health impact on the current practice guidelines for treating BP II MDE.