Antidepressant Efficacy of an Antiglutamatergic Agent in

抗谷氨酸药物的抗抑郁功效

• 批准号: 7312904
• 负责人: HUSSEINI K MANJI
• 金额: --
• 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/7312904
• 关键词: Antidepressant; Efficacy; Antiglutamatergic; Agent

The treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. 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. Finally, our group recently found in two separate studies that the glutamate modulating agent riluzole was effective in treatment-resistant unipolar and bipolar depression (Zarate et al 2004; Zarate et al. 2005). 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. In this study, we propose to extend our findings from open-label studies with riluzole in treatment-resistant depression by investigating its efficacy in a double-blind placebo-controlled study in bipolar depression. Patients, ages 18 to 70 years with a diagnosis of bipolar disorder I or II current episode depressed (without psychotic features), will be 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. Approximately 78 patients with acute bipolar depression will be enrolled in this study.

急性单相抑郁症的治疗已得到广泛研究。然而，尽管有多种抗抑郁药物可供使用，但临床试验表明，尽管有足够的剂量、持续时间和依从性，但仍有 30% 至 40% 的抑郁症患者对一线抗抑郁治疗没有反应。很少有研究检验躯体治疗对双相抑郁症急性期的疗效。因此，显然需要开发新的和改进的双相抑郁疗法。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。最后，我们的小组最近在两项独立的研究中发现，谷氨酸调节剂利鲁唑对难治性单相和双相抑郁症有效（Zarate 等人，2004 年；Zarate 等人，2005 年）。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。 在这项研究中，我们建议通过研究利鲁唑在双相抑郁症双盲安慰剂对照研究中的疗效，扩展利鲁唑治疗难治性抑郁症开放标签研究的结果。 年龄在 18 至 70 岁之间、诊断为双相情感障碍 I 型或 II 型当前发作抑郁（无精神病特征）的患者将被随机分配接受双盲治疗，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。 大约 78 名急性双相抑郁患者将参加这项研究。