Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

临床前和临床研究表明，调节谷氨酸能系统的药物可能会对情绪障碍患者产生治疗效果。抗抑郁药已被证明对这一系统有延迟的间接影响。拉莫三嗪是一种谷氨酸释放的抑制剂，是一种被批准的治疗双相情感障碍的药物。我们小组在两项单独的开放研究中发现，谷氨酸调节剂利鲁唑(谷氨酸释放的抑制剂，AMPA转运和谷氨酸重摄取的促进剂)对治疗难治性单相和双相抑郁有效。综上所述，这些数据表明，谷氨酸能系统可能在抑郁症的病理生理和治疗中发挥作用，而更直接减少谷氨酸能神经传递的药物可能代表了一类新的抗抑郁药物。 利鲁唑治疗难治性双相抑郁的疗效目前正在一项双盲安慰剂对照研究中进行测试。 年龄在18岁到70岁之间的双相情感障碍患者目前正处于严重的抑郁发作中，他们正在积极地被招募，并被随机分成双盲，接受利鲁唑(50-200毫克/天)或安慰剂治疗8周。急性疗效将通过在蒙哥马利-阿斯伯格抑郁量表中表现出更大的应答率来确定。 这项对照研究仍在进行中，并积极招募受试者。学习的盲目并没有被打破。

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.