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).

使用抗惊厥剂卡马西平(CBZ)，我们在 双盲试验急性反应约三分之二的急性 躁狂患者和三分之一的急性抑郁症患者。在许多 实例反应已在药物-安慰剂-药物(B-A-B)中得到确认 设计。锂强化的反应不充分也观察到在 躁狂和抑郁，尽管T3和T4的下降幅度更大 与单独使用任何一种药物相比。两种躁狂症的长期预防 CBZ也记录了抑郁发作，尽管 亚组患者表现出随时间推移而失去疗效(耐受性)和 停药一段时间后，这种情况可能是可逆的。病人 对卡马西平反应不足的患者可能对丙戊酸盐有反应，而- 反过来说。对锂的不良反应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，以及这些药物 似乎是锂耐受性双相情感障碍的重要临床选择 病人。抗惊厥药钙通道阻滞剂的积极作用 尼莫地平在Z01 MH 02635中得到了观察和总结。我们有 初步鉴定分化的临床和生物学标记物 情绪稳定剂的反应。其中包括快速自行车作为一种 锂和卡马西平反应差但反应良好的预测指标 他们的组合。颞叶高代谢与 对CBZ的反应良好，而额叶代谢不足似乎是一种 尼莫地平疗效的预测因子。盲目、随机、平行设计 两种具有新作用机制的新抗惊厥药物的研究方案 --加巴喷丁和拉莫三嗪--已获批准。内生性 在脑脊液中注射抗惊厥神经肽TRH 常规腰椎穿刺术8例。情绪改善，焦虑， 与假手术相比，自杀意念被观察到。 对大脑的重复经颅磁刺激(RTMS)正在进行 在随机患者中探索作为抗抑郁药和潜在的 替代一些原本需要的病人 电休克治疗(ECT)。