Efficacy of an Antiglutamatergic Agents in Treament-Resistant Deprepression

谷氨酸能的研究可能对情绪障碍的病理生理和治疗具有重要意义。拉莫三嗪是一种谷氨酸释放抑制剂，被批准用于治疗双相情感障碍。我们在两项独立的公开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）对治疗难治性单极和双相抑郁症有效。总的来说，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，而更直接地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。

The glutamatergic study may be important to the pathophysiology and treatment of mood disorders. Lamotrigine, an inhibitor of glutamate release, is an approved treatment for bipolar disorder. We 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. We are also testing the efficacy of riluzole in a 4-site study (Massachusetts General Hospital, Baylor College, Yale University and NIMH) as an add-on treatment in treatment-resistant depression. 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. Results of the add-on riluzole study in treatment-resistant unipolar depression should be completed in 2-3 years.