Efficacy of an Antiglutamatergic Agents in Treament-Resistant Deprepression

抗谷氨酸药物治疗难治性抑郁症的疗效

• 批准号: 8342144
• 负责人: Carlos Zarate
• 金额: $ 19.21万
• 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/8342144
• 关键词: Acute; Antidepressive Agents; Anxiety; Bipolar Depression; Bipolar Disorder; Clinical; Clinical Trials; Controlled Study; Data; Depressed mood; Double-Blind Method; Enhancers; Functional disorder; General Hospitals; Glutamates; Hamilton Rating Scale for Depression; Major Depressive Disorder; Manic; Massachusetts; Measures; Mental Depression; Montgomery and Asberg depression rating scale; Mood Disorders; National Institute of Mental Health; Outcome Measure; Patients; Phase; Placebos; Play; Randomized; Randomized Controlled Trials; Recruitment Activity; Research; Resistance; Riluzole; Role; Selective Serotonin Reuptake Inhibitor; Site; Study Subject; System; Testing; Therapeutic; Unipolar Depression; Universities; blind; college; depressive symptoms; dosage; efficacy testing; impression; improved; inhibitor/antagonist; lamotrigine; neurotransmission; novel; open label; placebo controlled study; primary outcome; response; reuptake; secondary outcome; trafficking

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.

谷氨酸能研究可能对情绪障碍的病理生理学和治疗很重要。拉莫三嗪是一种谷氨酸释放抑制剂，是一种经批准的治疗双相情感障碍的药物。我们在两项独立的开放研究中发现，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）对难治性单相和双相抑郁症有效。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学和治疗中发挥作用，并且更直接减少谷氨酸能神经传递的药物可能代表一类新型抗抑郁药。 利鲁唑治疗难治性双相抑郁症的疗效目前正在一项双盲安慰剂对照研究中进行测试。我们还在一项 4 中心研究（麻省总医院、贝勒学院、耶鲁大学和 NIMH）中测试利鲁唑作为难治性抑郁症的附加治疗的疗效。 急性疗效将通过在蒙哥马利-阿斯伯格抑郁评定量表中表现出更高的反应率来确定。 这项对照研究仍在进行中并积极招募受试者。研究盲目性尚未被打破。利鲁唑治疗难治性单相抑郁症的附加研究结果应在 2-3 年内完成。