Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom.
Curr Med Res Opin. 2012 Oct;28(10):1717-24. doi: 10.1185/03007995.2012.725035. Epub 2012 Sep 17.
The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder.
Patients entered this 52-week, open-label extension study after completing an 8-week lead-in study. Safety and tolerability were evaluated at regular intervals on the basis of spontaneously reported adverse events (AEs), clinical safety laboratory tests, vital signs, ECG and physical examination. Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
A total of 535 patients were treated and 61.3% (n = 328) completed the study, resulting in 393 patient years of exposure to vortioxetine. AEs reported by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, six patients had eight AEs related to sexual dysfunction. There were no clinically significant safety findings with respect to mean changes of vital signs, weight, ECG parameters, or clinical laboratory values. Patients entered the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 52 (OC). By the end of the study, the proportion of responders had increased from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a relapse rate (MADRS ≥22) of 9.7%.
As with all open-label studies, the conclusions that can be drawn are limited by the lack of a placebo control, making it difficult to assess causality of any changes in outcome measures. However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment.
This study has the ClinicalTrials.gov identifier: NCT00694304.
本研究的主要目的是评估研究药物沃替西汀（Lu AA21004）在治疗重度抑郁症患者的长期治疗中的安全性和耐受性。
在为期 8 周的导入研究完成后，患者进入这项为期 52 周的开放性扩展研究。根据自发报告的不良事件（AE）、临床安全实验室检查、生命体征、心电图和体格检查，定期评估安全性和耐受性。使用蒙哥马利-Åsberg 抑郁评定量表（MADRS）总分评估治疗效果。
共有 535 名患者接受了治疗，61.3%（n=328）完成了研究，患者暴露于沃替西汀的时间总计为 393 人年。报告发生率≥10%的不良事件为恶心、头痛和鼻咽炎。共有 6 名患者发生了 8 起与性功能障碍相关的不良事件。生命体征、体重、心电图参数或临床实验室值的平均变化无临床意义的安全性发现。患者进入扩展研究时的平均 MADRS 总分是 13.5±8.7。到第 52 周（OC）时，MADRS 总分平均降低（改善）了约 8 分，降至 5.5±6.0（OC）。研究结束时，应答者的比例从 63%增加到 94%（OC），缓解者（MADRS≤10）的比例从 42%增加到 83%（OC）。在这项研究开始时处于缓解状态（n=226）的患者，复发率（MADRS≥22）为 9.7%。
与所有开放性研究一样，由于缺乏安慰剂对照，因此可以得出的结论受到限制，难以评估任何结果测量变化的因果关系。然而，基于这些发现，沃替西汀（2.5、5、10mg/天）在 12 个月的治疗中显示出良好的安全性和耐受性，并保持有效性。
这项研究的 ClinicalTrials.gov 标识符为：NCT00694304。
