Acute Treatment of Bipolar II Depression

描述(由申请人提供)：这项探索性的第三阶段R21提案旨在提供关于未被研究的精神健康人群--双相II型障碍(BDII)--的急性治疗反应的数据。这种障碍的特征是严重的抑郁和其他人可以观察到的轻躁狂期。现在对这种诊断的稳定性有了明确的认识，对抑郁症状的严重性和频率的认识也增加了。总体严重程度、残疾和自杀风险被认为等同于双相I型障碍。 现对BDII治疗的现有文献进行综述。几乎没有对照的急性治疗试验来指导治疗建议，最近的治疗指南中也没有提到BDII的治疗。最广泛的数据支持锂(Li)作为一个治疗组。拉莫三嗪(LTG)的惊人新发现支持其在BDI急性抑郁和预防快速循环BDII方面的有效性。基于已有的研究，包括安全性和耐受性的评估，我们选择在这项先导性研究中评估LTG和LI。 我们提出了一项为期16周的随机开放临床试验，比较单一疗法LI和LTG对60名急性抑郁的BDII患者的疗效。一名医生和一名失明症状评价者将每两周看一次病人，总共16周。描述了用于维护患者安全的保障措施。主要目的将是比较LTG和LI的相对治疗效果。我们推测LTG在减少抑郁症状方面将比LI更有效。次要目标包括评估患者的耐受性、LTG转变为低躁狂症的可能性、生活质量和患者满意度。衡量标准将包括汉密尔顿抑郁症评定量表、蒙哥马利-阿斯伯格抑郁症评定量表、青年躁狂症评定量表、双相情感障碍临床全球评估以及其他生活质量、功能、身体症状和副作用的衡量标准。 虽然在这一人群中进行全面的干预试验显然是必要的，以建立有数据库的治疗建议，但收集试点数据以适当地提供动力并为更大规模试验的设计提供信息是至关重要的。这项先导性研究将提供全面干预试验所需的目标和样本量的数据。

DESCRIPTION (provided by applicant): This exploratory, stage 3 R21 proposal is designed to provide data on the acute treatment response of an understudied mental health population --bipolar II disorder (BDII). This disorder is characterized by major depression and periods of hypomania observable by others. There is now clear recognition of the stability of this diagnosis, and increased recognition of the severity and frequency of depressive symptoms. The overall severity, disability, and suicide risk is considered equal to bipolar I disorder. The available literature on treatment of BDII is reviewed. There are virtually no controlled acute treatment trials to direct treatment recommendations, nor is the treatment of BDII addressed in recent treatment guidelines. The most extensive data support lithium (Li) as one treatment group. Striking new findings with lamotrigine (LTG) support its efficacy in BDI acute depression and prophylaxis of rapid cycling BDII. Based on research done, including estimation of safety and tolerability, we chose to evaluate LTG and Li in this pilot study. We propose a randomized, open 16-week clinical trial comparing monotherapy Li versus LTG for sixty acutely depressed BDII patients. A physician and a blinded symptom rater will see patients every two weeks for a total of sixteen weeks. Safeguards are described to maintain patient safety. The primary aim will be to compare the relative treatment effectiveness of LTG versus Li. We hypothesize LTG will be more effective than Li at decreasing depressive symptoms. Secondary aims include assessment of tolerability, the potential of LTG to cause switching into hypomania, quality of life, and patient satisfaction. Measures will include the Hamilton Rating Scale for Depression, Montgomery-Asberg Rating Scale for Depression, Young Mania Rating Scale, Clinical Global Assessment for Bipolar Disorder, and other measures of quality of life, functioning, and physical symptoms and side effects. While full-scale intervention trials are clearly warranted in this population to establish databased recommendations for treatment, it is critical to collect pilot data to properly power and inform the design of a larger trial. This pilot study will provide data addressing the aims and sample size needed for a full-scale intervention trial.