Depression Clinical and Research Program, Massachusetts General Hospital, 55 Fruit St, Bulfinch 351, Boston, MA 02114, USA.
J Clin Psychiatry. 2011 Apr;72(4):473-9. doi: 10.4088/JCP.09m05131gry. Epub 2010 Nov 2.
Patients with major depressive disorder (MDD) and significant anxiety are less responsive to antidepressants than those without anxiety. In this post hoc analysis of patients with insomnia and comorbid anxious depression, eszopiclone cotherapy with a selective serotonin reuptake inhibitor (SSRI) was compared with placebo cotherapy.
Data were pooled from 2 randomized, double-blind, 8-week trials. One trial (conducted from January 2004 to October 2004) included patients with DSM-IV insomnia and comorbid MDD treated with fluoxetine concurrently with eszopiclone 3 mg/d or placebo. The other trial (conducted from July 2005 to April 2006) included patients with DSM-IV-TR insomnia and comorbid generalized anxiety disorder treated with escitalopram concurrently with eszopiclone 3 mg/d or placebo. Anxious depression was defined as a baseline 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 14 (excluding insomnia items) and an anxiety/somatization factor score ≥ 7. Treatment group differences were determined for mean changes in HDRS-17 scores (with and without insomnia items), HDRS anxiety/somatization scores, and response and remission rates. Severity of insomnia was assessed by the Insomnia Severity Index (ISI).
In the combined dataset, 347 of 1,136 patients (30.5%) had insomnia and comorbid anxious depression. Significant improvements in insomnia were observed for eszopiclone cotherapy relative to placebo cotherapy (mean change from baseline on the ISI: -11.0 vs -7.8, respectively; P < .001). There were greater reductions in HDRS-17 scores at week 8 following cotherapy with eszopiclone compared with placebo when the insomnia items were included (mean change: -14.1 vs -11.2, respectively; P < .01) or excluded (-10.6 vs -8.9; P < .01), but not for anxiety/somatization (-4.3 vs -4.1; P = .23). Response rates were greater for eszopiclone cotherapy than for placebo cotherapy (55.6% vs 42.0%, respectively; P = .01; 50.0% vs 44.4% when insomnia items were removed; P = .3). Remission rates were not significantly different (32.6% vs 27.2%, respectively; P = .28).
In this post hoc analysis of patients with insomnia and comorbid anxious depression derived from 2 trials, 8 weeks of eszopiclone therapy coadministered with an SSRI resulted in significantly greater improvements in insomnia, significantly greater reductions in HDRS-17 total score, and significantly greater HDRS-17 response rates compared with placebo coadministration. There were no significant differences in response rates (when insomnia items were excluded) and remission rates, as well as in anxiety/somatization scores. Further research is warranted to determine whether these modest antidepressant effects can be replicated, and anxiolytic effects demonstrated, when evaluated in a prospective manner.
与无焦虑症的患者相比，伴有重度抑郁障碍（MDD）和明显焦虑症的患者对抗抑郁药的反应较差。在这项针对伴有失眠和共病焦虑性抑郁症患者的事后分析中，佐匹克隆与选择性 5-羟色胺再摄取抑制剂（SSRI）联合治疗与安慰剂联合治疗进行了比较。
数据来自两项随机、双盲、8 周试验的汇总。一项试验（2004 年 1 月至 2004 年 10 月进行）纳入了 DSM-IV 失眠和共病 MDD 的患者，这些患者同时接受氟西汀治疗，并服用佐匹克隆 3mg/d 或安慰剂。另一项试验（2005 年 7 月至 2006 年 4 月进行）纳入了 DSM-IV-TR 失眠和共病广泛性焦虑症的患者，这些患者同时接受依西酞普兰治疗，并服用佐匹克隆 3mg/d 或安慰剂。焦虑性抑郁症的定义为基线时 17 项汉密尔顿抑郁评定量表（HDRS-17）评分≥14（不包括失眠项目）和焦虑/躯体化因子评分≥7。治疗组之间的差异通过 HDRS-17 评分（包括和不包括失眠项目）、HDRS 焦虑/躯体化评分、反应率和缓解率的平均变化来确定。失眠严重程度采用失眠严重程度指数（ISI）评估。
在联合数据集，1136 例患者中有 347 例（30.5%）患有失眠和共病焦虑性抑郁症。与安慰剂联合治疗相比，佐匹克隆联合治疗显著改善了失眠（ISI 自基线的平均变化：-11.0 与-7.8，分别；P<.001）。佐匹克隆联合治疗时，包括失眠项目（平均变化：-14.1 与-11.2，分别；P<.01）或不包括失眠项目（-10.6 与-8.9；P<.01）时，第 8 周时 HDRS-17 评分的降幅更大，但焦虑/躯体化评分无显著差异（-4.3 与-4.1；P=.23）。佐匹克隆联合治疗的反应率高于安慰剂联合治疗（分别为 55.6%和 42.0%；P=.01；当去除失眠项目时为 50.0%和 44.4%；P=.3）。缓解率无显著差异（分别为 32.6%和 27.2%；P=.28）。
在这项源自两项试验的失眠和共病焦虑性抑郁症患者的事后分析中，8 周的佐匹克隆联合 SSRI 治疗与安慰剂联合治疗相比，失眠显著改善，HDRS-17 总分显著降低，HDRS-17 反应率显著提高。但反应率（当排除失眠项目时）和缓解率以及焦虑/躯体化评分无显著差异。需要进一步研究以确定当以前瞻性方式评估时，这些适度的抗抑郁作用是否可以复制，以及是否可以显示出抗焦虑作用。
