Combination Therapy in Bipolar Rapid Cycling

描述(申请人提供)：使用双盲增强 停产设计，早期的锂维护研究表明 60%-80%的双相情感障碍患者的临床表现令人满意 回应。然而，这些较早的研究排除了锂难熔亚群 例如所有的双相II型障碍。当锂的响应率是 考虑到双相情感障碍的广泛范围，这一比例可能接近50 百分比。锂耐药患者中的一大类是快速循环者。 14%至53%的双相情感障碍患者周期较快 大多数是双相II型和女性。72%到82%的快速骑自行车者 对锂的反应不佳。因此，相当大比例的穷人 对锂的反应归因于快速循环。初步数据来自 MH-50165提示锂和异丙丙胺联合治疗的结果 在显著抗躁狂，但抗抑郁药疗效不明显的患者快速 骑自行车；75%的无反应可归因于顽固性抑郁症。 需要更广泛有效的养生方法。为应付这方面的需要，我们建议 比较锂、异丙丙胺和安慰剂三联疗法的安全性和有效性 拉莫三嗪至锂和异丙丙胺的双重方案。癌症化疗 试验采用了对平行手臂的随机分配来比较安全性 和2种部分有效、3种部分有效的化疗药物 有效的试剂；来自MH-50165的证据表明，快速循环是 充分的治疗--难治性，值得采用类似的研究 方法论。这项初步研究的主要目标是进行 三联方案与双联方案的相对疗效探讨 急性期和续发期未选定患者的“一线”治疗 抑郁症、轻躁狂症或躁狂症的门诊管理。建议进行的研究 将用作未来全面、STEP PROGRAIN多中心的试点数据 维护试用期。在修订后的竞争续签中，我们提出了 单中心，STEP计划附属，6个月，随机，双盲， 两种联合治疗方案的平衡平行组比较 在90名表现抑郁的快周期双相情感障碍患者中 三年期。

DESCRIPTION (provided by applicant): Using double-blind enriched discontinuation designs, early lithium maintenance studies demonstrated that 60-80 percent of patients with bipolar disorder had a satisfactory clinical response. However, these older studies excluded lithium-refractory subgroups such as all bipolar II disorder. When the response rate of lithium is considered across the wide spectrum of bipolar disorders, it may approach 50 percent. A large subgroup of lithium-resistant patients is rapid-cyclers. Fourteen to 53 percent of patients with bipolar disorder cycle rapidly and the majority is bipolar II and female. Seventy-two to 82 percent of rapid-cyclers exhibit poor response to lithium. Thus, a substantial percentage of poor response to lithium is attributable to rapid cycling. Preliminary data from MH-50165 suggest that combination therapy with lithium and divalproex results in marked antimanic, but modest antidepressant efficacy in patients with rapid cycling; 75 percent of non-response is attributable to resistant depression. More broadly effective regimens are needed. To address this need, we propose to compare the safety and efficacy of the triple regimen lithium, divalproex, and lamotrigine to the double-regimen lithium and divalproex. Cancer chemotherapy trials have employed random assignment to parallel arms to compare the safety and efficacy of 2 partially effective, chemotherapeutic agents to 3 partially effective agents; the evidence from MH-50165 suggests that rapid-cycling is sufficiently treatment-refractory to merit a study employing similar methodology. The primary objective of this pilot study is to conduct an exploration of the relative efficacy of the triple vs. double regimen as "first-line" therapy among unselected patients in the acute and continuation outpatient management of depression, hypomania, or mania. The proposed study will be used as pilot data for a future full-scale, STEP Prograin multicenter maintenance trial. In this revised competitive renewal, we propose a single-center, STEP-Program affiliated, 6-month, randomized, double-blind, balanced parallel-group comparison of these two regimens of combination therapy in 90 patients with rapid-cycling bipolar disorder presenting depressed over a three-year period.