Bipolar II Depression: Lithium, SSRI, or the Combination

描述（由申请人提供）：该基金旨在探索双相II型障碍（BDII）患者抑郁症的最佳治疗方法。BDII代表了一种严重的未充分研究的重要严重精神疾病，其特征是重度抑郁和轻躁狂时期。现在已经清楚地认识到双相情感障碍的这种诊断表型随时间的稳定性。进一步的研究表明，BDII的抑郁症状经常发生，其后果可能很严重，因为自杀风险高于BDI患者。治疗抑郁症BDII患者的标准治疗是单独使用情绪稳定剂或情绪稳定剂和抗抑郁药。然而，几乎没有专门针对BDII患者的对照急性治疗试验来支持这些建议的有效性。许多患有BDII的患者不喜欢服用情绪稳定剂的想法，而宁愿只服用抗抑郁药。一些开放性试验表明抗抑郁药单药治疗具有良好的安全性和耐受性。然而，人们担心抗抑郁药单药治疗可能会使这些患者的情绪不稳定。服用抗抑郁药作为单一疗法是否会加重疾病（即，增加转换成躁狂或骑自行车，或加剧轻躁狂）从未正式测试。我们提出了一项随机、双盲、为期16周的急性临床试验，比较舍曲林单药治疗与锂单药治疗与锂加舍曲林联合治疗207例急性抑郁发作的BDII患者的疗效和安全性。该应用程序旨在评估接受治疗方法的BDII抑郁症患者的急性治疗反应、轻躁狂/躁狂转换率和副作用。 主要目的是比较3种治疗策略的有效性、不良事件（例如， 转换速率）和副作用（例如，耐受性）。我们假设所有的治疗方法都是 在减少抑郁症状方面同样有效，但在转换为轻躁狂/躁狂的比率方面，治疗之间存在差异。我们还假设SSRI单药治疗的患者副作用的频率会显著降低。因此，次要目的包括评估患者满意度，这可能会影响临床环境中的依从性。

DESCRIPTION (provided by applicant): This grant proposes to explore the optimal treatment approach to depression in the patient with bipolar II disorder (BDII). BDII represents a critically understudied and important serious mental illness and is characterized by periods of major depression and periods of hypomania. There is now clear recognition of the stability of this diagnostic phenotype of bipolar disorder over time. Further research has revealed that the depressive symptoms in BDII occur frequently and the consequences of this can be severe, as the suicide risk is suggested to be higher than that in patients with BDI. The standard of care in treating depressed BDII patients is to use a mood stabilizer alone or a mood stabilizer and an antidepressant. However, there are virtually no controlled acute treatment trials specifically in patients with BDII to support the validity of these recommendations. Many patients with BDII dislike the idea of taking mood stabilizers and prefer instead to take only an antidepressant. Some open trials suggest good safety and tolerability of antidepressant monotherapy. Yet concerns exist that antidepressant monotherapy could destabilize mood in these patients. Whether taking an antidepressant as monotherapy actually exacerbates the illness (i.e., increases switches into mania or cycling, or intensifies hypomania) has never formally been tested. We propose a randomized, double-blind 16-week acute clinical trial comparing the efficacy and safety of sertraline monotherapy v. lithium monotherapy v. lithium plus sertraline combination in 207 patients with BDII in an acute depressive episode. The application is designed to assess acute treatment response, switch rates into hypomania/mania and side effects in patients with BDII depression undergoing treatment approaches. Primary aims are to compare the 3 treatment strategies in terms of effectiveness, adverse events (e.g., switch rates) and side effects (e.g., tolerability). We hypothesize that all treatment approaches will be equally efficacious in reducing depressive symptoms, but that there will be differences between treatments in regard to switch rates into hypomania/mania. We also hypothesize that the frequency of side effects will be significantly less in patients on SSRI monotherapy. Thus, secondary aims include assessment of patient satisfaction, which may affect compliance in the clinical setting.