Bipolar II Depression: Lithium, SSRI, or the Combination

描述（由申请人提供）：该资助旨在探索双相情感障碍（BDII）患者抑郁症的最佳治疗方法。BDII是一种尚未得到充分研究的重要严重精神疾病，其特征是周期性的重度抑郁和轻度躁狂。现在已经清楚地认识到这种双相情感障碍诊断表型随时间的稳定性。进一步的研究表明，BDII患者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。治疗抑郁的BDII患者的标准护理是单独使用情绪稳定剂或情绪稳定剂和抗抑郁药。然而，实际上没有针对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BDII患者不喜欢服用情绪稳定剂，而宁愿只服用抗抑郁药。一些公开试验表明抗抑郁药单一疗法具有良好的安全性和耐受性。然而，人们担心，抗抑郁药单一疗法可能会破坏这些患者的情绪。是否服用抗抑郁药作为单一疗法实际上加剧了疾病（即，增加转向躁狂或循环，或加剧轻躁狂）从未正式测试过。我们提出了一项随机、双盲、为期16周的急性临床试验，比较了207例急性抑郁发作的BDII患者舍曲林单药治疗、锂单药治疗和锂+舍曲林联合治疗的疗效和安全性。该应用程序旨在评估接受治疗的BDII抑郁症患者的急性治疗反应，转换为轻躁狂/躁狂的比率和副作用。

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.