VALPROATE VERSUS LITHIUM IN BIPOLAR RAPID CYCLING

虽然锂仍然是治疗双相情感障碍的首选， 只有60 -80%的典型双相患者具有令人满意的临床表现， 反应当考虑锂的响应率时， 广泛的双相情感障碍，它可能接近50%。大 耐锂躁狂患者亚组是快速循环者， Dunner和Fieve定义为4次或4次以上抑郁和轻度躁狂 或者说是狂热大约13-20%的双相情感障碍患者 快速循环，大多数是女性。多达72-82%的快速循环者 对锂的反应很差因此， 对锂的不良反应是基于快速 骑自行车尽管对照试验已经证明了 卡马西平治疗快速循环双相情感障碍 对卡马西平的反应经常随时间而恶化。 此外，其自身诱导和异源诱导药物代谢的能力 使其日常使用复杂化。这些发现表明， 的快速循环者对卡马西平和锂都有耐药性， 需要额外的情绪稳定剂 丙戊酸盐治疗急性和预防性疗效 我们最近报道了快速循环的双相情感障碍。这些 开放但前瞻性的试验，以及其他积极的报告 在快速循环中的有效性，表明需要对照试验。我们 建议采用改良随机分配，单中心，18个月，双- 丙戊酸盐和锂的盲态、平行组比较 门诊轻躁狂/躁狂预防性管理60例 患有快速循环的躁郁症本研究的主要目的 本研究旨在检验丙戊酸盐单药治疗 在预防性管理中比锂单药治疗有效 轻躁狂和躁狂。研究的主要疗效变量将 维持治疗期间至首次轻躁狂或躁狂复发的时间 根据研究诊断标准定义的单药治疗。次要疗效 将研究变量以进一步检验主要假设： 生活质量、轻躁狂总天数、轻躁狂总次数 发作和轻躁狂发作的严重程度。平均和最差评分 轻度躁狂和躁狂发作期间的抑郁评级将反映 每一集的质量都不一样关于抗抑郁药的数据 将收集疗效，包括首次抑郁复发的时间， 抑郁总天数、抑郁发作总次数以及平均和 抑郁严重程度的最差分数。这项研究将提供新的 描述丙戊酸盐与 锂在患者人群中具有高度的公共卫生意义。

Although lithium remains the treatment of choice for bipolar disorder, only 6O-80% of classic bipolar patients have a satisfactory clinical response. When the response rate of lithium is considered across the wide spectrum of bipolar disorders, it probably approaches 50%. A large subgroup of lithium-resistant manic patients are rapid cyclers, which is defined by Dunner and Fieve as 4 or more depressions and hypomanias or manias in a 12 month period. About 13-20% of bipolar patients become rapid cyclers and most are females. As many as 72-82% of rapid cyclers exhibit poor responses to lithium. Thus, a substantial percentage of poor response to lithium is accounted for on the basis of rapid cycling. Although controlled trials have demonstrated the efficacy of carbamazepine in the treatment of rapid-cycling bipolar disorder, the response to carbamazepine frequently deteriorates over time. Furthermore, its ability to autoinduce and heteroinduce drug metabolism complicates its routine use. These findings suggest substantial numbers of rapid cyclers become resistant to both carbamazepine and lithium and that additional mood stabilizers are needed. The acute and prophylactic efficacy of valproate in the management of the rapid-cycling bipolar disorder was recently reported by us. These open but prospective trials, as well as other positive reports of its efficacy in rapid cycling, indicate a need for controlled trials. We propose a modified random assignment, single center, 18 month, double- blind, parallel group comparison of valproate and lithium for the prophylactic outpatient management of hypomania/mania in 60 patients with rapid-cycling bipolar disorder. The primary objective of this study is to test the hypothesis that valproate monotherapy is more effective than lithium monotherapy in the prophylactic management of hypomania and mania. The primary efficacy variable for the study will be time to first hypomanic or manic relapse during maintenance monotherapy defined by Research Diagnostic Criteria. Secondary efficacy variables will be studied to further test the primary hypothesis: quality of life, total days hypomanic, total numbers hypomanic episodes, and severity of hypomanic episodes. Mean and worst score depression ratings during hypomanic and manic episodes will reflect the mixed quality of each individual episode. Data regarding antidepressant efficacy will be gathered including time to first depressive relapse, total days depressed, total number of depressed episodes, and mean and worst scores of depression severity. This study should provide novel data describing the safety and efficacy of valproate compared to lithium in a patient population with high public health significance.