Dunner David L, Goldstein David J, Mallinckrodt Craig, Lu Yili, Detke Michael J
Department of Psychiatry and Behavioral Sciences, University of Washington Center for Anxiety and Depression, Seattle, WA, USA.
Depress Anxiety. 2003;18(2):53-61. doi: 10.1002/da.10122.
Most patients with major depressive disorder (MDD) have symptoms of anxiety associated with their depression. Duloxetine, a potent and balanced dual serotonin and norepinephrine reuptake inhibitor, is effective in the treatmentof depression. We investigated its effects in treating the symptoms of anxiety in depressed patients. This investigation includes all the placebo-controlled studies of duloxetine in MDD but focuses on four trials in which duloxetine was superior to placebo on the primary outcome measure of the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score. Studies 1 and 2 included duloxetine at 60 mg/d (the recommended starting and therapeutic dose) and placebo. Study 3 included duloxetine 120 mg/d (administered as 60 mg b.i.d.), fluoxetine 20 mg/d, and placebo. Study 4 included duloxetine 40 mg/d (administered as 20 mg b.i.d.), duloxetine 80 mg/d (administered as 40 mg b.i.d.), paroxetine 20 mg/d, and placebo. Anxiety was assessed in all studies using the HAMD anxiety/somatization subfactor and the anxiety-psychic item (HAMD Item 10). Studies 3 and 4 also included the Hamilton Anxiety Rating Scale (HAMA). Across the four studies, duloxetine at doses of >/=60 mg was compared with placebo on 10 outcomes and with either paroxetine or fluoxetine on 6 outcomes. In 8 comparisons, mean improvement for duloxetine was significantly greater than placebo at the last study visit and/or across all study visits. In 3 comparisons, the mean improvement for duloxetine was significantly greater than paroxetine or fluoxetine. In these studies, duloxetine provided rapid relief of anxiety symptoms associated with depression. Previous reports have summarized duloxetine's efficacy in treating the core emotional symptoms and painful physical symptoms associated with depression. Duloxetine's efficacy in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical symptoms, may be attributed to dual reuptake inhibition of both serotonin and norepinephrine. Efficacy in these three key symptom domains may in turn explain the high probabilities of remission (43-57%) observed in these studies.
大多数重度抑郁症（MDD）患者伴有与抑郁相关的焦虑症状。度洛西汀是一种强效且平衡的5-羟色胺和去甲肾上腺素双重再摄取抑制剂，对抑郁症治疗有效。我们研究了其对抑郁患者焦虑症状的治疗效果。这项研究纳入了所有度洛西汀治疗MDD的安慰剂对照研究，但重点关注四项试验，在这四项试验中，度洛西汀在17项汉密尔顿抑郁评定量表（HAMD(17)）总分这一主要结局指标上优于安慰剂。研究1和2纳入了60mg/d的度洛西汀（推荐起始和治疗剂量）及安慰剂。研究3纳入了120mg/d的度洛西汀（每日两次，每次60mg给药）、20mg/d的氟西汀及安慰剂。研究4纳入了40mg/d的度洛西汀（每日两次，每次20mg给药）、80mg/d的度洛西汀（每日两次，每次40mg给药）、20mg/d的帕罗西汀及安慰剂。所有研究均使用HAMD焦虑/躯体化子因子和焦虑-精神项目（HAMD第10项）评估焦虑情况。研究3和4还纳入了汉密尔顿焦虑评定量表（HAMA）。在这四项研究中，剂量≥60mg的度洛西汀在10项结局指标上与安慰剂进行了比较，在6项结局指标上与帕罗西汀或氟西汀进行了比较。在8次比较中，度洛西汀在末次研究访视时和/或所有研究访视期间的平均改善程度显著大于安慰剂。在3次比较中，度洛西汀的平均改善程度显著大于帕罗西汀或氟西汀。在这些研究中，度洛西汀能迅速缓解与抑郁相关的焦虑症状。既往报告总结了度洛西汀在治疗与抑郁相关的核心情绪症状和疼痛躯体症状方面的疗效。度洛西汀在治疗与抑郁相关的广泛症状（包括情绪、焦虑和疼痛躯体症状）方面的疗效，可能归因于其对5-羟色胺和去甲肾上腺素的双重再摄取抑制作用。在这三个关键症状领域的疗效可能反过来解释了这些研究中观察到的较高缓解率（43%-57%）。
