McCarthy Brian, Bunn Hannah, Santalucia Morgan, Wilmouth Charlotte, Muzyk Andrew, Smith Colin M
Mood Treatment Center, Winston-Salem, NC, USA.
Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
Clin Psychopharmacol Neurosci. 2023 Nov 30;21(4):609-616. doi: 10.9758/cpn.23.1081. Epub 2023 Jul 17.
Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45-105 mg for patients with major depressive disorder saw significant reductions in their Montgomery-Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45-105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery-Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery-Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.
抑郁症是全球发病和死亡的重要原因。尽管有多种治疗抑郁症的药物选择，但治疗受到治疗反应延迟或不完全、缓解率低以及不良反应的限制，因此需要有效、起效快且耐受性更好的替代方案。本综述的目的是描述右美沙芬-安非他酮（Auvelity）的安全性和有效性，这是一种经美国食品药品监督管理局批准用于治疗成人重度抑郁症的药物。右美沙芬通过对N-甲基-D-天冬氨酸受体的非竞争性拮抗作用和σ-1激动作用来调节谷氨酸信号传导，而安非他酮则通过抑制CYP2D6来提高右美沙芬的生物利用度。在一项针对重度抑郁症患者的3期试验中，使用45-105毫克右美沙芬-安非他酮的患者与安慰剂相比，蒙哥马利-Åsberg抑郁评定量表总分显著降低。一项将45-105毫克右美沙芬-安非他酮与安非他酮单药治疗进行比较的2期试验导致蒙哥马利-Åsberg抑郁评定量表评分显著降低。在两项临床试验中，使用右美沙芬-安非他酮两周内蒙哥马利-Åsberg抑郁评定量表都有变化。在两项研究中，右美沙芬-安非他酮的缓解率和有效率都显著更高。该药物在两项试验中耐受性良好，最常见的不良事件被评为轻度至中度。两项关于右美沙芬-安非他酮的长期开放标签研究显示，蒙哥马利-Åsberg抑郁评定量表评分大幅降低，并在12个月和15个月的治疗期内得以维持。在两项长期研究中，缓解率接近70%，而有效率大于80%。这些数据表明，右美沙芬-安非他酮是一种治疗抑郁症的有效、起效快且耐受性良好的选择，能使很大一部分患者实现缓解。
