Treatment of Bipolar Type II Major Depression

描述（由申请人提供）：本申请，题为“双相II型重度抑郁症的治疗”，是一个竞争性的继续资助，是基于我们以前的NIMH资助的研究结果，题为“双相II型障碍的复发预防”（R01 MH 060353）。双相II型（BP II）重度抑郁发作（MDE）是本提案的主题，影响了2.5%的美国成年人口，估计每年的医疗费用为400亿美元。BP II型疾病是一种不同于BP I型疾病的独特临床实体，其特征在于MDE占优势，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。对抗抑郁药（AD）诱导的躁狂转换发作的担忧导致目前的实践指南建议使用情绪稳定剂（MS）单药治疗BP II MDE，并避免AD单药治疗。到目前为止，还没有对照临床试验来测试这些经验指南的有效性。我们的初步BP II MDE研究结果表明，氟西汀或文拉法辛单药治疗可能是一种安全有效的BP II MDE的初始治疗，躁狂转换率较低。基于这些观察结果，我们现在提出（具体目标1）：“BP II MDE初始AD单药治疗与MS单药治疗的相对安全性和有效性如何？和“初始AD与MS单药治疗BP II MDE的相对躁狂转换率是多少？”“为了回答这些问题，BP II MDE患者将接受为期12周的随机平行组比较文拉法辛单药治疗与锂单药治疗。我们假设AD单药治疗的疗效上级MS单药治疗，并且两种治疗条件之间的躁狂转换率相似。我们还将询问（具体目标#2）：“在从MDE中恢复的BP II患者中，继续AD与MS单药治疗的疗效如何？在恢复的BP II型MDE患者中，持续AD与MS单药治疗6个月的躁狂转换率是多少？“为了回答这个问题，在初始治疗期间有反应的患者将接受文拉法辛与锂单药治疗的6个月持续治疗。我们假设AD单药治疗的疗效上级MS单药治疗，并且两种治疗条件之间的躁狂转换率相似。如果我们的假设是正确的，我们相信，这些结果可能有一个重要的公共卫生影响，目前的实践指南治疗BP II MDE。

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.