Maurizio Fava, Luca Pani, Sara De Martin, Andrew J Cutler, Charles W Gorodetzky, Frank J Vocci, Frank L Sapienza, Thomas R Kosten, Cornelia Kröger, Paggard Champasa, Clotilde Guidetti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo
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Safety was assessed from adverse events, laboratory parameters, vital signs, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Efficacy assessments used measures of depression, anxiety, sleep, sexual function, cognitive function, and quality of life. The safety population comprised patients who received at least 1 dose of study drug, and the full analysis set (FAS) comprised patients who had at least 1 postbaseline efficacy assessment.</p><p><p><b>Results:</b> Safety population included 624 patients; FAS included 586 patients (384 <i>rollover</i> and 202 de novo); mean age was 42.9 (13.6) years, and mean baseline Montgomery-Asberg Depression Rating Scale (MADRS10) was 34.5 (4.8). Most common treatment-related treatment emergent adverse events were headache (4.6%), nausea (4.2%), and dizziness (2.6%). There were no signals of meaningful neurological, cardiovascular, metabolic, or sexual adverse events and no case of suicide or suicidal attempt. For the FAS, mean (SD) change from baseline for MADRS10 at 3, 6, 9, and 12 months was -20.1 (10.7), -21.0 (10.8), -21.6 (10.7), and -21.6 (10.4). For the de novo population, mean (SD) was -19.9 (10.0), -19.9 (10.4), -20.1 (10.2), and -22.5 (9.7). Consistent improvements occurred with other tested efficacy measures.</p><p><p><b>Conclusions:</b> Long-term treatment with esmethadone was safe and well tolerated. 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引用次数: 0
摘要
背景：艾美沙酮是一种新型n -甲基- d -天冬氨酸受体（NMDAR）非竞争性拮抗剂，正在开发中作为重度抑郁症（MDD）的辅助治疗药物。方法：这项为期12个月的开放标签研究评估了艾美沙酮在符合DSM-5标准的MDD患者中的安全性和有效性，这些患者完成了3项双盲研究中的1项（翻转），以及之前没有参加艾美沙酮研究的MDD患者（de novo）。安全性从不良事件、实验室参数、生命体征、心电图和哥伦比亚自杀严重程度评定量表进行评估。疗效评估采用抑郁、焦虑、睡眠、性功能、认知功能和生活质量等指标。安全人群包括接受至少1剂研究药物的患者，完整分析集（FAS）包括至少1次基线后疗效评估的患者。结果：安全人群624例；FAS纳入586例患者（384例复发，202例新生）；平均年龄为42.9（13.6）岁，平均基线蒙哥马利-阿斯伯格抑郁评定量表（MADRS10）为34.5（4.8）岁。最常见的治疗相关不良事件是头痛（4.6%）、恶心（4.2%）和头晕（2.6%）。没有有意义的神经、心血管、代谢或性不良事件的信号，也没有自杀或自杀企图的病例。对于FAS， MADRS10在3、6、9和12个月与基线相比的平均（SD）变化为-20.1（10.7）、-21.0（10.8）、-21.6（10.7）和-21.6（10.4）。对于新生群体，平均（SD）为-19.9(10.0),-19.9(10.4),-20.1（10.2）和-22.5（9.7）。其他测试的疗效指标也出现了一致的改善。结论：长期应用艾美沙酮治疗安全、耐受性好。艾美沙酮抗抑郁疗效持续12个月以上。试验注册：ClinicalTrials.gov标识符：NCT04855760。
Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study.
Background: Esmethadone is a novel N-methyl-D-aspartate receptor (NMDAR) uncompetitive antagonist in development as adjunctive treatment for major depressive disorder (MDD).
Methods: This 12-month, open-label study evaluated the safety and efficacy of esmethadone in patients with MDD meeting DSM-5 criteria who completed 1 of 3 double-blind studies (rollover) and in patients with MDD and no prior participation in esmethadone studies (de novo). Safety was assessed from adverse events, laboratory parameters, vital signs, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Efficacy assessments used measures of depression, anxiety, sleep, sexual function, cognitive function, and quality of life. The safety population comprised patients who received at least 1 dose of study drug, and the full analysis set (FAS) comprised patients who had at least 1 postbaseline efficacy assessment.
Results: Safety population included 624 patients; FAS included 586 patients (384 rollover and 202 de novo); mean age was 42.9 (13.6) years, and mean baseline Montgomery-Asberg Depression Rating Scale (MADRS10) was 34.5 (4.8). Most common treatment-related treatment emergent adverse events were headache (4.6%), nausea (4.2%), and dizziness (2.6%). There were no signals of meaningful neurological, cardiovascular, metabolic, or sexual adverse events and no case of suicide or suicidal attempt. For the FAS, mean (SD) change from baseline for MADRS10 at 3, 6, 9, and 12 months was -20.1 (10.7), -21.0 (10.8), -21.6 (10.7), and -21.6 (10.4). For the de novo population, mean (SD) was -19.9 (10.0), -19.9 (10.4), -20.1 (10.2), and -22.5 (9.7). Consistent improvements occurred with other tested efficacy measures.
Conclusions: Long-term treatment with esmethadone was safe and well tolerated. The antidepressant efficacy of esmethadone was sustained over 12 months.
期刊介绍：
For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.
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