VALPROATE VERSUS LITHIUM IN BIPOLAR RAPID CYCLING

尽管锂仍然是双相情感障碍的首选治疗方法， 只有60%-80%的典型双相情感障碍患者的临床表现令人满意 回应。当考虑到锂的响应率时 在广泛的双相情感障碍中，这一比例可能接近50%。大号 抗锂躁狂症患者的亚群是快速循环者，这 被Dunner和Fieve定义为4个或更多的抑郁和低躁狂 或者在12个月的时间里疯狂。大约13%-20%的双相情感障碍患者 骑自行车速度快的人，大多数是女性。多达72%-82%的快速自行车手 对锂的反应很差。因此，相当大比例的 对锂的不良反应是基于快速的 骑自行车。尽管对照试验已经证明了该药的疗效。 卡马西平治疗快周期双相情感障碍 对卡马西平的反应经常会随着时间的推移而恶化。 此外，其自身诱导和异源诱导药物代谢的能力 使其常规使用复杂化。这些发现表明了相当多的数字 的快速循环者对卡马西平和锂产生抗药性 需要额外的情绪稳定剂。 丙戊酸盐治疗慢性阻塞性肺疾病的急性和预防性疗效观察 快速循环型双相情感障碍是我们最近报道的。这些 公开的但预期的试验，以及关于其 在快速循环中的有效性，表明需要进行对照试验。我们 建议修改随机分配，单中心，18个月，双- 丙戊酸锂与丙戊酸锂的盲法平行对照研究 门诊预防性管理轻躁狂/躁狂症60例 患有快速循环的双相情感障碍。这样做的主要目标是 研究是为了检验丙戊酸盐单一疗法更多的假说 预防管理中锂离子疗法比单一锂疗法更有效 轻躁狂和躁狂症。这项研究的主要疗效变量将 在维护期间是第一次躁狂或躁狂复发的时候 研究诊断标准定义的单一疗法。二次功效 将对变量进行研究，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，以及轻躁狂发作的严重性。平均分和最差分 轻度躁狂和躁狂发作期间的抑郁评分将反映 每一集的质量参差不齐。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、抑郁发作总数、平均值和 抑郁严重程度的最差分数。这项研究应该为我们提供新的 描述丙戊酸盐安全性和有效性的数据与 锂在患者人群中具有很高的公共卫生意义。

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.