Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

最近的临床前研究表明，抗抑郁药可能会对多巴胺能系统产生延迟的间接影响。临床资料提示谷氨酸释放抑制剂拉莫三嗪和NMDA拮抗剂氯胺酮可能具有抗抑郁作用。我们的小组在两项独立的研究中发现，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。总之，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。 目前，我们正在双相抑郁症的双盲安慰剂对照研究中测试利鲁唑在难治性抑郁症中的疗效。 正在积极招募年龄为18 - 70岁的诊断为双相情感障碍当前发作抑郁的患者，并随机分配至双盲治疗组，接受利鲁唑（50-200 mg/天）或安慰剂治疗8周。将通过使用指定标准证明更高的缓解率来确定急性疗效。 随机对照研究仍在进行中，并积极招募受试者。研究设盲尚未破盲。

Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Clinical data suggests that lamotrigine an inhibitor of glutamate release and the NMDA antagonist ketamine may have antidepressant effects. Our group found in two separate 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. Together, 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. We are currently testing the efficacy of riluzole in treatment-resistant depression in a double-blind placebo-controlled study in bipolar depression. Patients, ages 18 to 70 years with a diagnosis of bipolar disorder current episode depressed 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 using specified criteria. The randomized controlled study is still ongoing and actively recruiting subjects. The study blind has not been broken.