Raskin Joel, Goldstein David J, Mallinckrodt Craig H, Ferguson Margaret B
Lilly Research Laboratories, Eli Lilly Canada, 3650 Danforth Avenue, Scarborough, Ontario, Canada M1N 2E8.
J Clin Psychiatry. 2003 Oct;64(10):1237-44. doi: 10.4088/jcp.v64n1015.
Depression is a chronic recurring disorder and guidelines recommend long-term therapy. This clinical trial evaluated the long-term (1 year) safety and efficacy of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, in patients with DSM-IV major depressive disorder.
This was an open-label, 52-week, multinational clinical trial in outpatients (age > or = 18 years) who received duloxetine at 80 mg/day (administered 40 mg twice daily) to 120 mg/day (administered 60 mg twice daily) for up to 1 year.
A total of 1279 patients had postbaseline data. Of these, 520 were exposed to duloxetine for at least 360 days, yielding approximately 808 patient-years of total exposure. Mean changes in Clinical Global Impressions-Severity of Illness scale (CGI-S) score, 17-item Hamilton Rating Scale for Depression total score and subfactor scores, Beck Depression Inventory-II score, and Sheehan Disability Scale score and mean Patient Global Impression-Improvement scale (PGI-I) scores all showed highly significant (p <.001) improvements at all assessment times. The estimated probabilities of improvement in CGI-S and PGI-I scores at week 1 were 40.4% and 59.2%, respectively, and at week 2 were 70.0% and 78.3%. The estimated probabilities of remission at weeks 6, 28, and 52 were 50.8%, 75.6%, and 81.8%, respectively. Adverse events led to discontinuation in 218 patients (17.0%). The most frequent specific events leading to discontinuation were nausea (1.5%), somnolence (1.4%), vomiting (0.9%), hypomania (0.8%), pregnancy (0.8%), dizziness (0.6%), insomnia (0.6%), and hypertension (0.5%). Treatment-emergent adverse events that were reported by > 10% of patients included nausea, insomnia, headache, somnolence, dry mouth, dizziness, constipation, sweating increase, anxiety, diarrhea, and fatigue. Most events occurred early in the study. Of those events that first occurred or worsened after discontinuation, only dizziness (8.3%) occurred in more than 5% of patients. Mean changes from baseline to last observation for standing and supine pulse were less than 2 b.p.m. Mean changes in blood pressure (< 1.0 mm Hg), corrected QT interval (< 1 msec), and body weight (2.4 kg [5.3 lb]) were not clinically significant. Laboratory analyses varied across visits, and mean changes after 52 weeks were generally close to zero. The incidence of laboratory values above or below normal limits at any time during treatment was low.
Duloxetine was effective, safe, and well tolerated in the long-term treatment of major depression at a dose of 80 to 120 mg/day in this study.
抑郁症是一种慢性复发性疾病，指南推荐长期治疗。本临床试验评估了度洛西汀（一种5-羟色胺和去甲肾上腺素双重再摄取抑制剂）对符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的重度抑郁症患者的长期（1年）安全性和疗效。
这是一项开放标签、为期52周的多国门诊患者（年龄≥18岁）临床试验，患者接受度洛西汀治疗，剂量为80毫克/天（每日两次，每次40毫克）至120毫克/天（每日两次，每次60毫克），最长治疗1年。
共有1279例患者有基线后数据。其中，520例患者接受度洛西汀治疗至少360天，总暴露时间约为808患者年。临床总体印象-疾病严重程度量表（CGI-S）评分、17项汉密尔顿抑郁量表总分及各因子分、贝克抑郁量表-II评分、希恩残疾量表评分的平均变化，以及患者总体印象-改善量表（PGI-I）评分在所有评估时间均显示出高度显著（p<.001）的改善。第1周时CGI-S和PGI-I评分改善的估计概率分别为40.4%和59.2%，第2周时分别为70.0%和78.3%。第6周、28周和52周时缓解的估计概率分别为50.8%、75.6%和81.8%。不良事件导致218例患者（17.0%）停药。导致停药最常见的具体事件为恶心（1.5%）、嗜睡（1.4%）、呕吐（0.9%）、轻躁狂（0.8%）、妊娠（0.8%）、头晕（0.6%）、失眠（0.6%）和高血压（0.5%）。报告的发生率超过10%的治疗中出现的不良事件包括恶心、失眠、头痛、嗜睡、口干、头晕、便秘、出汗增加、焦虑、腹泻和疲劳。大多数事件发生在研究早期。在停药后首次出现或加重的事件中，只有头晕（8.3%）在超过5%的患者中出现。从基线到最后一次观察，站立位和仰卧位脉搏的平均变化小于2次/分钟。血压（<1.0毫米汞柱）、校正QT间期（<1毫秒）和体重（2.4千克[5.3磅]）的平均变化无临床意义。各次访视的实验室分析结果不同，52周后的平均变化一般接近零。治疗期间任何时间实验室值高于或低于正常范围的发生率较低。
在本研究中，度洛西汀以80至120毫克/天的剂量长期治疗重度抑郁症有效、安全且耐受性良好。
