Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder

右美沙芬 安非他酮 安慰剂 重性抑郁障碍 内科学 心理学 医学 随机对照试验 麻醉 戒烟 扁桃形结构 病理 替代医学
作者
Dan V. Iosifescu,Amanda Jones,Cedric O’Gorman,Caroline Streicher,Samantha Feliz,Maurizio Fava,Herriot Tabuteau
出处
期刊:The Journal of Clinical Psychiatry [Physicians Postgraduate Press, Inc.]
卷期号:83 (4) 被引量:86
标识
DOI:10.4088/jcp.21m14345
摘要

Objective: Altered glutamatergic neurotransmission has been implicated in the pathogenesis of depression. This trial evaluated the efficacy and safety of AXS-05 (dextromethorphan-bupropion), an oral N-methyl-D-aspartate (NMDA) receptor antagonist and σ1 receptor agonist, in the treatment of major depressive disorder (MDD). Methods: This double-blind, phase 3 trial, was conducted between June 2019 and December 2019. Patients with a DSM-5 diagnosis of MDD were randomized in a 1:1 ratio to receive dextromethorphan-bupropion (45 mg-105 mg tablet) or placebo, orally (once daily for days 1–3, twice daily thereafter) for 6 weeks. The primary endpoint was the change from baseline to week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Other efficacy endpoints and variables included MADRS changes from baseline at week 1 and 2, clinical remission (MADRS score ≤ 10), clinical response (≥ 50% reduction in MADRS score from baseline), clinician- and patient-rated global assessments, Quick Inventory of Depressive Symptomatology-Self-Rated, Sheehan Disability Scale, and quality of life measures. Results: A total of 327 patients were randomized: 163 patients to dextromethorphan-bupropion and 164 patients to placebo. Mean baseline MADRS total scores were 33.6 and 33.2 in the dextromethorphan-bupropion and placebo groups, respectively. The least-squares mean change from baseline to week 6 in MADRS total score was −15.9 points in the dextromethorphan-bupropion group and −12.0 points in the placebo group (least-squares mean difference, −3.87; 95% confidence interval , −1.39 to −6.36; P = .002). Dextromethorphan-bupropion was superior to placebo for MADRS improvement at all time points including week 1 (P = .007) and week 2 (P < .001). Remission was achieved by 39.5% of patients with dextromethorphan-bupropion versus 17.3% with placebo (treatment difference, 22.2; 95% CI, 11.7 to 32.7; P < .001), and clinical response by 54.0% versus 34.0%, respectively (treatment difference, 20.0%; 95% CI, 8.4%, 31.6%; P < .001), at week 6. Results for most secondary endpoints were significantly better with dextromethorphan-bupropion than with placebo at almost all time points (eg, CGI-S least-squares mean difference at week 6, −0.48; 95% CI, −0.48 to −0.79; P = .002). The most common adverse events in the dextromethorphan-bupropion group were dizziness, nausea, headache, somnolence, and dry mouth. Dextromethorphan-bupropion was not associated with psychotomimetic effects, weight gain, or increased sexual dysfunction. Conclusions: In this phase 3 trial in patients with MDD, treatment with dextromethorphan-bupropion (AXS-05) resulted in significant improvements in depressive symptoms compared to placebo starting 1 week after treatment initiation and was generally well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04019704
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
iFan完成签到 ,获得积分10
2秒前
4秒前
blackswan完成签到,获得积分10
4秒前
4秒前
八宝粥完成签到,获得积分10
5秒前
zhangjiegxf发布了新的文献求助10
5秒前
19880818完成签到,获得积分10
6秒前
6秒前
Orange应助Mmmm采纳,获得10
7秒前
徐醉蝶完成签到,获得积分10
7秒前
高兴的悟空完成签到,获得积分10
8秒前
包容新蕾完成签到 ,获得积分10
8秒前
弱于一般人类完成签到,获得积分10
9秒前
Ouyang完成签到 ,获得积分10
9秒前
Jarvis Lin发布了新的文献求助10
9秒前
八宝粥发布了新的文献求助10
9秒前
9秒前
任斯发布了新的文献求助10
10秒前
黄金蛋饺发布了新的文献求助10
10秒前
pluto应助科研通管家采纳,获得10
11秒前
春悠然应助科研通管家采纳,获得10
11秒前
高高应助科研通管家采纳,获得10
12秒前
高高应助科研通管家采纳,获得10
12秒前
情怀应助科研通管家采纳,获得10
12秒前
春悠然应助科研通管家采纳,获得10
12秒前
漂亮明辉完成签到,获得积分10
12秒前
CipherSage应助科研通管家采纳,获得10
12秒前
Wind应助科研通管家采纳,获得10
12秒前
xx完成签到,获得积分10
12秒前
搜集达人应助科研通管家采纳,获得10
12秒前
高高应助科研通管家采纳,获得10
12秒前
Jasper应助科研通管家采纳,获得30
12秒前
13秒前
高高应助科研通管家采纳,获得10
13秒前
13秒前
13秒前
13秒前
momo末流主发布了新的文献求助10
14秒前
zf发布了新的文献求助10
14秒前
高分求助中
(禁止应助)【重要!!请各位详细阅读】【科研通的精品贴汇总】 10000
Semantics for Latin: An Introduction 1099
Biology of the Indian Stingless Bee: Tetragonula iridipennis Smith 1000
Robot-supported joining of reinforcement textiles with one-sided sewing heads 740
镇江南郊八公洞林区鸟类生态位研究 500
Thermal Quadrupoles: Solving the Heat Equation through Integral Transforms 500
Corpus Linguistics for Language Learning Research 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4139320
求助须知:如何正确求助?哪些是违规求助? 3676275
关于积分的说明 11620352
捐赠科研通 3370382
什么是DOI,文献DOI怎么找? 1851340
邀请新用户注册赠送积分活动 914489
科研通“疑难数据库(出版商)”最低求助积分说明 829266