Dopamine Agonist/Select Serotonin Reuptake Inhibibitor

尽管有各种各样的抗抑郁药，但30%至40%的重度抑郁症患者对一线抗抑郁药（例如，选择性5-羟色胺再摄取抑制剂[SSRIs]）治疗，尽管有足够的剂量、持续时间和依从性。此外，这些药物可能需要数周至数月才能达到其全部效果，与此同时，患者继续遭受其症状，并继续处于自我伤害以及对其个人和职业生活造成损害的风险中。因此，显然需要开发新的和改进的治疗难治性重性抑郁症的治疗剂，其更有效并具有快速起效。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，选择性降钙素再摄取抑制剂（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一单独药剂更有效。因此，有理由认为，具有其他作用机制的抗抑郁药的其他组合在组合时可能具有优于具有单一作用机制的抗抑郁药的上级协同效应。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。类似地，初步临床研究表明与影响血清素和多巴胺系统的联合治疗的协同作用。总之，这些数据表明，影响血清素和多巴胺系统的治疗将比使用单一机制的药物更有效。我们建议在难治性抑郁症患者中比较选择性多巴胺能激动剂和SSRI的组合。据我们所知，这将是迄今为止唯一的对照双盲研究，将检查从治疗开始时给予的5-羟色胺和多巴胺组合的疗效。 年龄在18岁或以上、诊断为重度抑郁症（无精神病特征）的患者将随机接受选择性多巴胺能受体激动剂和SSRI联合治疗或任一种药物单独治疗6周。将通过使用指定标准证明更高的缓解率来确定急性疗效。约85例急性重度抑郁症患者将入组研究。

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.