ANTICONVULSANTS IN LITHIUM-REFRACTORY BIPOLAR PATIENTS

锂难治性双相情感障碍患者的抗惊厥药

• 批准号: 5203736
• 负责人: R M POST
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203736
• 关键词: anticonvulsants; biomarker; bipolar depression; bipolar depression depressed phase; bipolar depression manic phase; brain metabolism; carbamazepine; clinical trials; combination chemotherapy; drug interactions; drug tolerance; frontal lobe /cortex; human subject; human therapy evaluation; lithium; mental disorder chemotherapy; nimodipine; prognosis; psychopharmacology; temporal lobe /cortex; thyrotropin releasing hormone; valproate

Using the anticonvulsant carbamazepine (CBZ) we have documented in double-blind trials acute response in approximately two-thirds of acutely manic patients and one-third of acutely depressed patients. In many instances response has been confirmed in a drug-placebo-drug (B-A-B) design. Lithium augmentation of inadequate response is also observed in both mania and depression despite greater decrements in T3 and T4 compared with either agent alone. Long-term prophylaxis of both manic and depressive episodes has also been documented with CBZ although a subgroup of patients shows loss of efficacy over time (tolerance) and this may be reversible with a period of time off medications. Patients who are inadequately responsive to CBZ may respond to valproate and vice- versa. Many of the predictors of poor response to lithium may be associated with good response to CBZ or valproate, and these agents appear to be important clinical options for lithium-refractory bipolar patients. 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. A blind, randomized, parallel design protocol to study two new anticonvulsants with novel mechanisms of action -- GABApentin and lamotrigine -- have been approved. The endogenous anticonvulsant neuropeptide TRH has been administered into the CSF during a routine lumbar puncture in 8 patients. Improvement in mood, anxiety, and suicidal preoccupation was observed compared with the sham procedure. Repeated transcranial magnetic stimulation (rTMS) of the brain is being explored in randomized patients as an antidepressant and potential substitute for some patients who would otherwise require electroconvulsive therapy (ECT).

使用抗惊厥药卡马西平（CBZ），我们已经记录在 双盲试验急性反应，约三分之二的急性 躁狂症患者和三分之一的急性抑郁症患者。 在许多 在药物-安慰剂-药物（B-A-B）中证实了缓解的实例 设计 在以下患者中也观察到锂增强反应不足： 躁狂和抑郁症，尽管T3和T4下降更大 与单独使用任何一种药物相比。 长期预防躁狂和 CBZ也记录了抑郁发作， 患者亚组显示疗效随时间丧失（耐受性）， 这可能是可逆的，与一段时间的药物。 患者 对CBZ反应不充分的患者可能对丙戊酸盐和副丙戊酸盐有反应， 亦然许多对锂反应不良的预测因素可能是 与CBZ或丙戊酸盐的良好反应相关，这些药物 似乎是锂难治性双极的重要临床选择 患者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反应不良但反应良好的预测因子 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。 盲态、随机、平行设计 研究两种具有新作用机制的新抗惊厥药的方案 -- GABApentin和拉莫三嗪--已被批准。 内生 抗惊厥神经肽TRH已被注入CSF， 常规腰椎穿刺8例。 改善情绪焦虑 与假手术相比，观察到自杀倾向。 大脑的重复经颅磁刺激（rTMS）正在被 在随机化患者中探索作为抗抑郁药和潜在的 代替了一些病人， 电休克疗法（ECT）。