BACKGROUND Kappa-opioid antagonism may possess antidepressant properties. We assessed, in a proof-of-concept pilot trial among patients with major depressive disorder with inadequate response to antidepressants, the efficacy of adjunctive CERC-501 (formerly LY2456302), a kappaselective opioid receptor antagonist. METHODS In a Sequential Parallel Comparison Design study, patients were pre-randomized to: a) 10 mg/d of CERC-501 for 6 days, b) 20 mg/d of CERC-501 for 6 days, c) placebo for 3 days followed by 10 mg/d of CERC- 501 for 3 days, d) placebo for 3 days followed by 20 mg/d of CERC-501 for 3 days, or e) placebo for 6 days. RESULTS The study was terminated early by the National Institute of Mental Health due to slow enrollment (N = 8). The weighted mean difference of changes (drug vs placebo) in the 6-item Hamilton Depression Rating Scale (HAMD-6) (primary outcome measure) (1.28), Montgomery-Åsberg Depression Rating Scale (MADRS) (2.33), Perceived Stress Scale (1.01), Symptoms of Depression Questionnaire (9.17), Positive Affect Scale (PAS) (6.39), Symptom Questionnaire (SQ) Depression scale (2.94), SQ Anger- Hostility scale (1.67), and Patient-Reported Outcomes Measurement Information System Satisfaction with Participation in Discretionary Social Activities (4.67) scores were all numerically but not statistically greater for CERC-501 than for placebo. CONCLUSIONS Although the small sample size limits the ability to draw conclusions, results suggest that CERC-501 may have antidepressant effects. Additional studies are necessary to further explore these effects of CERC-501.

中文翻译：

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卡帕选择性阿片受体拮抗剂增强治疗抵抗性抑郁症的双盲、安慰剂对照、概念验证试验

背景κ-阿片样物质拮抗作用可能具有抗抑郁特性。我们在对抗抑郁药反应不足的重度抑郁症患者中进行的概念验证试点试验中，评估了辅助性 CERC-501（以前称为 LY2456302）（一种 kappa 选择性阿片受体拮抗剂）的疗效。方法 在一项顺序平行比较设计研究中，患者被预先随机分配至：a) 10 mg/d CERC-501，持续 6 天，b) 20 mg/d CERC-501，持续 6 天，c) 安慰剂，持续 3 天然后是 10 毫克/天的 CERC-501 持续 3 天，d) 安慰剂持续 3 天，然后是 20 毫克/天的 CERC-501 持续 3 天，或 e) 安慰剂持续 6 天。结果 由于招募缓慢（N = 8），美国国家心理健康研究所提前终止了该研究。6 项汉密尔顿抑郁量表 (HAMD-6)（主要结果测量）（1.28）、Montgomery-Åsberg 抑郁量表（MADRS）（2.33）、感知压力量表中变化的加权平均差异（药物与安慰剂） (1.01)、抑郁症状问卷 (9.17)、积极情绪量表 (PAS) (6.39)、症状问卷 (SQ) 抑郁量表 (2.94)、SQ 愤怒-敌意量表 (1.67) 和患者报告结果测量信息系统CERC-501 参与自主社交活动的满意度 (4.67) 分数在数值上均高于安慰剂，但在统计学上并不高于安慰剂。结论 尽管样本量小限制了得出结论的能力，但结果表明 CERC-501 可能具有抗抑郁作用。需要进一步研究以进一步探索 CERC-501 的这些影响。