Gartlehner Gerald, Gaynes Bradley N, Hansen Richard A, Thieda Patricia, DeVeaugh-Geiss Angela, Krebs Erin E, Moore Charity G, Morgan Laura, Lohr Kathleen N
Danube University, Krems, Austria.
Ann Intern Med. 2008 Nov 18;149(10):734-50. doi: 10.7326/0003-4819-149-10-200811180-00008.
Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing.
To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults.
MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research.
Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included.
Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes.
If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression.
Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy.
Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.
第二代抗抑郁药在重度抑郁症、心境恶劣障碍和亚综合征性抑郁的治疗中占主导地位。关于其相对益处和危害的证据仍在不断积累。
比较第二代抗抑郁药（安非他酮、西酞普兰、度洛西汀、艾司西酞普兰、氟西汀、氟伏沙明、米氮平、奈法唑酮、帕罗西汀、舍曲林、曲唑酮和文拉法辛）治疗成人抑郁症的益处和危害。
检索1980年至2007年4月的MEDLINE、EMBASE、PsychLit、Cochrane对照试验中央注册库和国际药学文摘，仅限于英文文章。人工检索相关综述文章的参考文献列表，并查阅药品评价和研究中心数据库以识别未发表的研究。
两名研究人员独立评审摘要和全文文章。纳入了6篇之前质量为良好或中等的系统评价或荟萃分析，以及155项质量为良好或中等、为期至少6周的双盲、安慰剂对照或直接比较的随机对照试验。对于危害研究，还纳入了35项观察性研究，每项研究至少有100名参与者且随访至少12周。
研究人员使用标准方案提取关于研究设计、质量相关细节、资金来源、研究背景、患者和结局的数据。
如果数据充足，则对直接比较试验进行荟萃分析，以确定治疗反应的相对益处以及特定抑郁评定量表上的加权平均差异。如果没有足够的证据，则使用荟萃回归和网状荟萃分析进行校正间接比较。基于203项研究，第二代抗抑郁药在治疗重度抑郁症的疗效或有效性方面没有实质性差异；然而，特定不良事件的发生率和起效时间有所不同。关于这些药物治疗心境恶劣障碍和亚综合征性抑郁的相对疗效、有效性或危害，证据不足，无法得出结论。
校正间接比较存在方法学局限性，不能确凿地排除疗效差异。
目前的证据并不支持基于疗效和有效性的差异而选择一种第二代抗抑郁药优于另一种。起效时间和不良事件方面的其他差异可能与药物选择相关。
