Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

临床前和临床研究表明，调节多巴胺能系统的药物可能对情绪障碍患者产生治疗作用。抗抑郁药已被证明对该系统有延迟的间接影响。拉莫三嗪是一种谷氨酸释放抑制剂，是一种被批准用于治疗双相情感障碍的药物。我们的小组在两项独立的开放性研究中发现，谷氨酸调节剂利鲁唑（谷氨酸释放抑制剂，AMPA运输和谷氨酸再摄取增强剂）对难治性单极和双相抑郁症有效。总的来说，这些数据表明，多巴胺能系统可能在抑郁症的病理生理学和治疗中发挥作用，并且更直接地减少多巴胺能神经传递的药物可能代表一类新的抗抑郁药。 利鲁唑治疗难治性双相抑郁症的疗效目前正在双盲安慰剂对照研究中进行测试。 参与者，年龄18至70岁，目前在一个严重的抑郁发作的双相情感障碍正在积极招募和随机双盲，治疗接受利鲁唑（50-200毫克/天）或安慰剂8周的时间。将通过证明蒙哥马利-阿斯伯格抑郁评定量表的缓解率更高来确定急性疗效。 这项对照研究仍在进行中，并积极招募受试者。研究盲态尚未被打破。

Preclinical and clinical studies suggest that drugs that modulate the glutamatergic system might result in therapeutic effects in patients with mood disorders. Antidepressants have been demonstrated to have delayed indirect effects on this system. Lamotrigine, an inhibitor of glutamate release, is an approved treatment for bipolar disorder. Our group found in two separate open studies that the glutamate modulating agent riluzole (inhibitor of glutamate release, and enhancer of AMPA trafficking and glutamate reuptake) was effective in treatment-resistant unipolar and bipolar depression. Collectively, these data suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants. The efficacy of riluzole in treatment-resistant bipolar depression is currently being tested in a double-blind placebo-controlled study. Participants, ages 18 to 70 years with bipolar disorder currently in a major depressive episode are actively being recruited and randomized to double-blind, treated to receive either riluzole (50-200 mg/day) or placebo for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate in the Montgomery-Asberg Depression Rating scale. This controlled study is still ongoing and actively recruiting subjects. The study blind has not been broken.