Combination Therapy in Bipolar Rapid Cycling

描述（由申请人提供）：使用双盲富集 停药设计，早期锂维持研究表明， 60%-80%的双相情感障碍患者的临床表现令人满意， 反应然而，这些较早的研究排除了锂难治性亚组 例如所有双相II型障碍。当锂的反应速率为 在广泛的双相情感障碍中，它可能接近50 百分之锂耐药患者的一大亚组是快速循环者。 14%到53%的双相情感障碍患者周期迅速， 大多数是双相II型和女性。72%到82%的快速循环者 对锂的反应很差。因此，很大一部分穷人 对锂的响应归因于快速循环。的初步数据 MH-50165表明锂和双丙戊酸钠联合治疗的结果 在显著的抗躁狂，但适度的抗抑郁疗效的患者快速 骑自行车; 75%的无反应可归因于顽固性抑郁症。 需要更广泛有效的治疗方案。为了满足这一需求，我们建议 比较锂、双丙戊酸钠和 拉莫三嗪和双丙戊酸钠的双重方案癌症化疗 试验采用随机分配到平行组来比较 以及2种部分有效的化疗剂对3种部分有效的化疗剂的疗效 有效的药物; MH-50165的证据表明，快速循环是 足够难治，值得采用类似的研究 方法论这项试点研究的主要目的是进行一项 探索三联方案与双联方案的相对疗效， 急性期和持续期慢性胰腺炎患者的“一线”治疗 抑郁、轻躁狂或躁狂的门诊管理。拟定研究 将用作未来全规模STEP多中心试验的试验数据 维持性试验。在这次修订后的竞争性续约中，我们建议 单中心、STEP项目附属、6个月、随机、双盲， 这两种联合治疗方案的平衡平行组比较 在90例快速循环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.