NIMODIPINE IN LITHIUM-REFRACTORY BIPOLAR PATIENTS

尼莫地平治疗锂难治性双相情感障碍患者

• 批准号: 3781501
• 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/3781501
• 关键词: anticonvulsants; antidepressants; bipolar depression; bipolar depression depressed phase; bipolar depression manic phase; calcium channel; calcium channel blockers; calcium metabolism; carbamazepine; clinical trials; combination chemotherapy; drug administration rate /duration; human subject; human therapy evaluation; mental disorder chemotherapy; psychopharmacology; relapse /recurrence; verapamil

Utilization of the calcium channel blocker nimodipine in affective disorders is based on several empirical and theoretical rationales. The L-type calcium channel blocker verapamil has been reported effective in the treatment of acute mania but not depression, and nimodipine has a different profile of effects compared with verapamil. It is more lipid soluble and blocks cocaine-induced hyperactivity and dopamine overflow and is also a better anticonvulsant in several model systems. Positive response to nimodipine has been observed in one of five patients with rapid but not ultradian cycling disorder and this was confirmed in an on- off-on (B-A-B) design. Three patients with ultra-ultra rapid cycling (ultradian cycling) showed complete or partial responses to the double- blind administration of nimodipine. The partial responder was confirmed in the B-A-B design and a more complete response was achieved with the addition of carbamazepine. Since carbamazepine has recently been described to inhibit calcium influx through the NMDA receptor in cerebellar granule cells, these data raise the possibility that drugs with differential effects on calcium channels may be useful in refractory patients. One patient with recurrent brief depression responded dramatically to the blind institution of nimodipine, relapsed on placebo substitution, and re-responded with reinstitution of active drug (B-A-B- A); this patient continued to show improvement when verapamil was substituted for nimodipine. These data suggest the utility of further exploring the clinical profile of nimodipine in refractor affective disorders and of the potential of altered calcium metabolism in this illness.

钙通道阻滞剂尼莫地平在情感性痴呆中的应用 疾病是基于几个经验和理论的理由。 的 据报道，L型钙通道阻滞剂维拉帕米对 治疗急性躁狂症而非抑郁症，尼莫地平具有 与维拉帕米相比，效果不同。 它是更多的脂质 可溶性和阻断可卡因引起的多动症和多巴胺溢出 并且在几种模型系统中也是较好的抗惊厥剂。积极 尼莫地平的反应已被观察到在一个五名患者， 快速但不是超日周期紊乱，这在一项研究中得到了证实。 关-开（B-A-B）设计。 3例超超快速循环患者 （ultradian循环）显示完全或部分反应的双重- 尼莫地平盲法给药。 部分应答者被确认 在B-A-B设计中， 添加卡马西平。 由于卡马西平最近被 被描述为抑制通过NMDA受体的钙内流， 小脑颗粒细胞，这些数据提高了药物 对钙通道具有不同的作用， 患者 1例复发性短暂抑郁症患者 戏剧性地进入尼莫地平的盲人机构， 替换，并通过活性药物的重新使用而再次应答（B-A-B- A）;当维拉帕米被用于治疗时，该患者继续显示出改善。 代替尼莫地平。 这些数据表明，进一步 尼莫地平治疗难治性情感障碍的临床研究 疾病和改变钙代谢的潜力， 病