Dopamine Agonist/Select Serotonin Reuptake Inhibibitor

尽管有广泛的抗抑郁药物可用，30%至40%的重度抑郁症患者对一线抗抑郁药(如选择性5-羟色胺再摄取抑制剂[SSRIs])治疗没有反应，尽管有足够的剂量、持续时间和依从性。此外，这些药物可能需要几周到几个月的时间才能完全发挥作用，在此期间，患者继续遭受症状的折磨，继续面临自我伤害的风险，以及对他们的个人和职业生活的伤害。因此，显然有必要开发新的和改进的治疗难治性重度抑郁症的疗法，这些疗法更有效，起效更快。临床前和临床研究表明，具有联合作用机制的抗抑郁药(例如，选择性5-羟色胺再摄取抑制剂(SSRI)和去甲肾上腺素再摄取抑制剂的组合)在实现缓解方面可能比任何一种药物更有效。因此，顺理成章的是，抗抑郁药与其他作用机制的其他组合在结合时可能具有优于具有单一作用机制的抗抑郁药的协同效应。临床前和临床研究表明，多巴胺能系统可能在抑郁症的病理生理学中发挥重要作用。临床前研究表明，在抑郁症动物模型中，SSRI和选择性D3受体激动剂的组合具有协同抗抑郁作用。同样，初步临床研究表明，影响5-羟色胺和多巴胺系统的联合治疗具有协同作用。总而言之，这些数据表明，影响5-羟色胺和多巴胺系统的治疗将比使用单一机制的药物更有效。我们建议比较选择性多巴胺能激动剂和SSRI在难治性重度抑郁症患者中的联合应用。据我们所知，这将是迄今为止唯一一项对照双盲研究，将检查从治疗开始就给予5-羟色胺和多巴胺组合的疗效。 年龄在18岁或以上，被诊断为严重抑郁症(没有精神病特征)的患者将被随机分成两组，一组是选择性多巴胺受体激动剂和SSRI，另一组是单独用药，为期6周。急性疗效将通过使用特定标准显示更大的缓解率来确定。大约85名患有急性重度抑郁症的患者将参加这项研究。

Despite the availability of a wide range of antidepressant drugs, 30% to 40% of patients with major depression fail to respond to first-line antidepressant (e.g., selective serotonin reuptake inhibitors [SSRIs]) treatment, despite adequate dosage, duration, and compliance. Furthermore, these medications may take weeks to months to achieve their full effects, and in the meantime patients continue to suffer from their symptoms and continue to be at risk of self-harm as well as harm to their personal and professional lives. Thus, there is a clear need to develop novel and improved therapeutics for treatment-resistant major depression that are more effective and have a rapid onset of action. Preclinical and clinical studies suggest that antidepressants with a combined mechanism of action (e.g., combination of a selective serotonin-reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor) may be more effective than either agent alone in achieving remission. Thus, it stands to reason that other combinations of antidepressants with other mechanisms of action when combined may have a synergistic effect that is superior to an antidepressant with a single mechanism of action. Preclinical and clinical studies suggest that the dopaminergic system may play a major role in the pathophysiology of depression. Preclinical studies suggest synergistic antidepressant effects with the combination of a SSRI and a selective D3 receptor agonist in animal models of depression. Similarly, preliminary clinical studies suggest synergism with combination treatment that affects the serotonin and dopamine systems. Together, these data suggest that treatments which affect the serotonin and dopamine systems will be more effective than agents which use a single mechanism. We propose to compare the combination of a selective dopaminergic agonist and a SSRI in patients with treatment-resistant major depression. To our knowledge, this will be the only controlled double-blind study to date that will examine the efficacy of a serotonin and dopamine combination given from the start of treatment. Patients, ages 18 years or older, with a diagnosis of major depression (without psychotic features), will be randomized to the combination of a selective dopaminergic receptor agonist and a SSRI or either drug alone for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater remission rate using specified criteria. Approximately 85 patients with acute major depression will be enrolled in the study.