Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
J Psychiatr Res. 2010 Apr;44(6):356-63. doi: 10.1016/j.jpsychires.2009.09.013. Epub 2009 Nov 11.
The current study sought to test the efficacy and safety of the novel selective norepinephrine reuptake inhibitor LY2216684 compared to placebo in patients with major depressive disorder (MDD). Escitalopram was used as a control for assay sensitivity. Adult outpatients with MDD, confirmed at screening by the Mini International Neuropsychiatric Interview, a Self-Rated Quick Inventory of Depressive Symptomatology (QIDS-SR) score of at least 12 and a Clinical Global Impression-Severity Score of at least 4, were randomly assigned to LY2216684 (N=269), placebo (N=138), or escitalopram (N=62). Efficacy, safety, and tolerability outcomes were compared during 8 weeks of double-blind treatment. LY2216684 plasma concentrations were measured. LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale (HAM-D(17)) total score. Escitalopram demonstrated significant improvement compared to placebo on the HAM-D(17) total score, suggesting adequate assay sensitivity. Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo. Headache, nausea, constipation, dry mouth, and insomnia were the most frequently reported adverse events in the LY2216684 group. A 3-6 beats per minute mean increase from baseline in pulse rate was observed in the LY2216684 group. LY2216684 plasma concentrations increased as the dose increased from 3 mg to 12 mg. The results of this initial investigation of LY2216684's efficacy suggest that it may have antidepressant potential. More definitive data to confirm this is necessary. Its safety profile does not preclude further clinical development.
本研究旨在测试新型选择性去甲肾上腺素再摄取抑制剂 LY2216684 与安慰剂相比在重度抑郁症（MDD）患者中的疗效和安全性。依地普仑被用作检测灵敏度的对照。符合筛选时使用的 MINI 国际神经精神访谈、自评快速抑郁症状量表（QIDS-SR）评分至少 12 分和临床总体印象-严重程度评分至少 4 分的 MDD 成年门诊患者，被随机分配到 LY2216684（N=269）、安慰剂（N=138）或依地普仑（N=62）组。在 8 周的双盲治疗期间比较疗效、安全性和耐受性结果。测量 LY2216684 的血浆浓度。在汉密尔顿抑郁评定量表（HAM-D（17））总分的主要分析中，与安慰剂相比，LY2216684 未显示出统计学上的显著改善。与安慰剂相比，依地普仑在 HAM-D（17）总分上显示出显著改善，表明检测灵敏度足够。与安慰剂相比，LY2216684 和依地普仑在患者自评的 QIDS-SR 总分上均显示出统计学上的显著改善。头痛、恶心、便秘、口干和失眠是 LY2216684 组中最常报告的不良事件。与基线相比，LY2216684 组的脉搏率平均增加了 3-6 次/分钟。随着剂量从 3 毫克增加到 12 毫克，LY2216684 的血浆浓度增加。LY2216684 疗效初步研究的结果表明，它可能具有抗抑郁潜力。需要更明确的数据来证实这一点。其安全性特征不排除进一步的临床开发。
