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），我们已记录在 大约三分之二的急性反应急性反应 躁狂患者和三分之一的急性抑郁患者。 许多人 实例响应已在药物（B-A-B）中得到证实 设计。 在 尽管T3和T4减少了躁狂症和抑郁症 与仅任何一个代理相比。 两种躁狂的长期预防 抑郁发作也已记录在CBZ中，尽管 患者的亚组显示出随着时间的推移（公差）和 通过一段时间的休假，这可能是可逆的。 患者 对CBZ反应不足的人可能会对丙丙酸酯和副反应 Versa。对锂反应不良的许多预测因素可能是 与对CBZ或丙戊酸盐的良好反应有关，这些试剂 似乎是锂症状双极性的重要临床选择 患者。抗惊厥钙通道阻滞剂的积极作用 在Z01 MH 02635中观察到了Nimodipine。 初步鉴定的差异的临床和生物标记 情绪稳定器之间的反应。 这些包括快速骑自行车作为一个 预测对锂和CBZ的反应不佳，但良好的反应 结合在一起。 颞叶超定代谢与 对CBZ的良好反应，而额叶的低代谢似乎是 Nimodipine反应的预测指标。 盲人，随机，平行设计 研究两种具有新型作用机理的新抗惊厥药的协议 - 加巴喷丁和拉莫三嗪 - 已获批准。 内源性 抗惊厥神经肽TRH已在CSF中施用 8例患者的常规腰穿。 情绪改善，焦虑， 与假手术相比，观察到自杀率置。 大脑的重复经颅磁刺激（RTMS）正在 在随机患者中作为抗抑郁药和潜力探索 代替一些否则需要的患者 电击疗法（ECT）。