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治疗中的应用 疾病是基于几个经验和理论原理。 这 据报道，L 型钙通道阻滞剂维拉帕米可有效治疗 尼莫地平可以治疗急性躁狂症，但不能治疗抑郁症， 与维拉帕米相比，效果不同。 是脂质比较多 可溶并阻止可卡因引起的多动症和多巴胺溢出 在多种模型系统中也是更好的抗惊厥药。积极的 五名患者中的一名观察到对尼莫地平的反应 快速但非超电循环障碍，这一点在一项正在进行的研究中得到证实 关-开 (B-A-B) 设计。 三名超超快速循环患者 （超循环）显示出对双重反应的完全或部分反应 盲目给予尼莫地平。 部分响应者已得到确认 在 B-A-B 设计中，通过以下方式实现了更完整的响应 添加卡马西平。 由于卡马西平最近 描述为抑制钙通过 NMDA 受体流入 小脑颗粒细胞，这些数据提出了药物的可能性 对钙通道有不同的影响，可能有助于治疗难治性 患者。 一名患有复发性短暂抑郁症的患者做出了回应 盲目服用尼莫地平，服用安慰剂后病情复发 替换，并重新使用活性药物（B-A-B- 一个）;当使用维拉帕米时，该患者的病情持续改善 替代尼莫地平。 这些数据表明进一步的效用 探讨尼莫地平治疗屈光情感障碍的临床概况 疾病和改变钙代谢的潜力 疾病。