ANTICONVULSANTS IN LITHIUM-REFRACTORY BIPOLAR PATIENTS

在发现急性和预防效果的 抗惊厥药卡马西平（CBZ）和丙戊酸盐（VPA），我们有 43%和27%的患者记录到疗效丧失（可能是通过耐受性）， 患者分别。 算法，包括切换到药物， 不同的作用机制和联合治疗的使用正在被 探讨了 抗惊厥钙通道阻滞剂的积极作用 尼莫地平已被观察并总结在Z 01 MH 02635中。我们有 初步确定的临床和生物学标志物的差异 情绪稳定剂的反应。 其中包括快速循环， 对锂和CBZ反应不良的预测因子，但反应良好 他们的组合。 颞叶高代谢与 对CBZ的反应良好，而额叶代谢减退似乎是一个 尼莫地平反应的预测因子。 在许多情况下， 在安慰剂-药物-安慰剂-药物（B-A-B-A）中的个体患者中证实 设计 这种新方法可能比传统方法更有价值 设计，这是特别不适合的变量介绍 治疗躁郁症，非常昂贵，而且很少得到资助。 的患者 对一种情绪稳定抗惊厥药反应不充分， 回应另一个。 一项盲法、随机化、平行组设计方案 评价两种具有新作用机制的新抗惊厥药 与安慰剂加巴喷丁和拉莫三嗪相比， 前12例患者中有6例在CGI上反应良好， 拉莫三嗪内源性抗惊厥神经肽TRH已被 在8例常规腰椎穿刺中， 患者 试图将TRH转化为临床相关的范式， 最初通过每日胃肠外TRH给药实现，尽管 对这些治疗中产生的治疗效果的耐受性- 在几个月的时间里，顽固的人。显著 观察到情绪、焦虑和自杀倾向的改善 与假LP手术相比。 重复经颅磁共振 大脑的rTMS正在随机试验中探索 作为一种潜在的抗抑郁药在第一次开放研究之后， (in Neuroreport），在活动期间观察到显著改善， 而不是交叉试验中的假手术期。 随机第三 比较20 Hz、1 Hz和假rTMS的研究正在进行中。

Following finding the acute and prophylactic efficacy of the anticonvulsants carbamazepine (CBZ) and valproate (VPA) we have documented loss of efficacy (presumably via tolerance) in 43% and 27% of patients, respectively. Algorithms including switching to drugs with different mechanisms of action and use of combination therapy are being explored. Positive effects of the anticonvulsant calcium channel blocker nimodipine have been observed and summarized in Z01 MH 02635. We have preliminarily identified clinical and biological markers of differential response among the mood stabilizers. These include rapid cycling as a predictor of poor response to both lithium and CBZ, but a good response to their combination. Temporal lobe hypermetabolism is associated with good response to CBZ, while frontal lobe hypometabolism appears to be a predictor of nimodipine response. In many instances response has been confirmed in individual patients in a placebo-drug-placebo-drug (B-A-B-A) design. This new methodology may prove more valuable than traditional designs, which are particularly ill suited to the variable presentations of bipolar illness, very expensive, and rarely funded. Patients who are inadequately responsive to one mood stabilizing anticonvulsant may respond to another. A blind, randomized, parallel group design protocol evaluating two new anticonvulsants with novel mechanisms of action against placebo - gabapentin and lamotrigine - has preliminarily shown good response on the CGI in six of the first 12 patients randomized to lamotrigine. The endogenous anticonvulsant neuropeptide TRH has been administered into the CSF during a routine lumbar puncture in eight patients. Attempts to convert TRH to a clinically relevant paradigm were initially achieved with daily parenteral TRH administration, although tolerance to the therapeutic effects developed in these treatment- refractory individuals over the course of several months. Significant improvement in mood, anxiety, and suicidal preoccupation was observed compared with the sham LP procedure. Repeated transcranial magnetic stimulation (rTMS) of the brain is being explored in randomized trials as a potential antidepressant modality. Following the first open study (in Neuroreport), significant improvement was observed during active but not sham phase in patients in a crossover trial. A randomized third study comparing 20 Hz, 1 Hz, and sham rTMS is in progress.