Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto, Toronto, ON, Canada.
J Clin Pharm Ther. 2010 Apr;35(2):177-88. doi: 10.1111/j.1365-2710.2009.01050.x.
Controversy exists whether serotonin-norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs).
To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure.
Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007.
Included studies were those head-to-head randomized trials comparing remission (HAMD-17 <or=7-8, MADRS <or=10-12) after 8-12 weeks of therapeutic doses of SSRIs or SNRIs in patients diagnosed with MDD were targeted for analysis. Reviews, letters, commentaries, economic studies, etc. were excluded. Studies were reviewed by two independent researchers. Where disagreements occurred in study selection, a consensus approach was used.
Targeted outcome data included number of patients achieving remission, withdrawing from therapy due to lack of efficacy (LoE) and/or adverse drug reactions (ADRs), and total patients in trial. A random effects model combined intent-to-treat (ITT) and per-protocol (PP) odds ratio (OR), and remission and dropout rates. Chi-square assessed heterogeneity. Quality assessment was done using Downs-Black checklist.
Thirty-three studies were identified; 18 were rejected (patients had co-morbidities in 7, outcomes differed in 5, different follow-up in 3, and three reviews). Fifteen head-to-head trials of 3094 patients, average age was 41.9 +/- 11.9 years (for SNRIs) and 41.6 +/- 12.1 years (for SSRIs), P = 0.941. All analyses displayed non-heterogeneity (P > 0.05). The OR (under ITT) was 1.27 (1.06-1.52 95% CI) favoring SNRIs. Meta-analytic remission rates were 48.5 +/- 3.2% and 41.9 +/- 4.2% for SNRIs and SSRIs, respectively. The meta-analytic difference in remission rates between drugs was 5.7% (P = 0.007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3.2% difference, P < 0.001). Dropout rates due to LoE were non-significant between studied groups (P > 0.05).
Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.
与选择性 5-羟色胺再摄取抑制剂（SSRIs）相比，5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）是否具有更好的疗效仍存在争议。
在理想的临床条件下，比较使用 SSRIs 或 SNRIs 治疗成人重度抑郁症（MDD）的临床结局，包括研究设计和结局测量。
检索了 Medline、Embase 和 Cochrane Library 电子数据库，检索时间为 2007 年 7 月之前。
纳入的研究为直接比较治疗剂量 SSRIs 或 SNRIs 8-12 周后缓解（HAMD-17 <或=7-8，MADRS <或=10-12）的头对头随机试验，旨在分析 MDD 患者。排除综述、信件、评论、经济研究等。由两位独立研究人员对研究进行审查。如果在研究选择上存在分歧，则采用共识方法。
目标结局数据包括达到缓解的患者人数、因缺乏疗效（LoE）和/或药物不良反应（ADR）而退出治疗的患者人数以及试验中的总患者人数。采用随机效应模型合并意向治疗（ITT）和方案（PP）比值比（OR）以及缓解率和脱落率。卡方检验用于评估异质性。使用 Downs-Black 清单进行质量评估。
共确定了 33 项研究，其中 18 项被排除（7 项患者合并症，5 项结局不同，3 项随访不同，3 项为综述）。15 项头对头试验纳入 3094 例患者，平均年龄为 41.9 +/- 11.9 岁（SNRIs）和 41.6 +/- 12.1 岁（SSRIs），P = 0.941。所有分析均显示无异质性（P > 0.05）。ITT 下的 OR 为 1.27（95%CI 为 1.06-1.52），有利于 SNRIs。SNRIs 和 SSRIs 的缓解率分别为 48.5 +/- 3.2%和 41.9 +/- 4.2%。药物间缓解率的 meta 分析差异为 5.7%（P = 0.007）。由于 ADR 导致的停药率 SNRIs 高于 SSRIs（差异为 3.2%，P < 0.001）。由于 LoE 导致的研究组间停药率无显著性差异（P > 0.05）。
与 SSRIs 相比，5-羟色胺和去甲肾上腺素再摄取抑制剂在治疗 MDD 时具有统计学意义，但无临床意义。
