Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

抗谷氨酸药物对双相抑郁症的抗抑郁功效

• 批准号: 7969398
• 负责人: MILES A. HERKENHAM
• 金额: $ 60.16万
• 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/7969398
• 关键词: Acute; Age; Antidepressive Agents; Anxiety; Bipolar Depression; Bipolar Disorder; Clinical; Clinical Data; Clinical Trials; Controlled Study; Data; Diagnosis; Double-Blind Method; Enhancers; Functional disorder; Glutamates; Hamilton Rating Scale for Depression; Ketamine; Manic; Measures; Montgomery and Asberg depression rating scale; N-Methylaspartate; Outcome Measure; Patients; Phase; Placebos; Play; Randomized; Randomized Controlled Trials; Recruitment Activity; Research; Resistance; Riluzole; Role; Specific qualifier value; System; Therapeutic; Unipolar Depression; blind; depressed; depression; depressive symptoms; dosage; efficacy testing; impression; improved; inhibitor/antagonist; lamotrigine; neurotransmission; novel; open label; placebo controlled study; preclinical study; primary outcome; response; reuptake; secondary outcome; trafficking

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.

最近的临床前研究表明，抗抑郁药可能对谷氨酸能系统产生延迟的间接影响。临床数据表明，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）对难治性单相和双相抑郁症有效。总之，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。 我们目前正在一项双相抑郁症双盲安慰剂对照研究中测试利鲁唑治疗难治性抑郁症的疗效。 目前正在积极招募年龄为 18 至 70 岁、诊断为双相情感障碍当前发作抑郁的患者，并随机进行双盲治疗，接受利鲁唑（50-200 毫克/天）或安慰剂，为期 8 周。急性疗效将通过使用指定标准证明更高的反应率来确定。 随机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。