Department of Psychiatry, Harvard Medical School, Psychopharmacology Program and International Consortium for Psychotic and Mood Disorders Research, Mailman Research Center, McLean Division of Massachusetts General Hospital, Boston, MA, USA.
Neuropsychopharmacology. 2012 Mar;37(4):851-64. doi: 10.1038/npp.2011.306. Epub 2011 Dec 14.
Antidepressant-placebo response-differences (RDs) in controlled trials have been declining, potentially confounding comparisons among older and newer drugs. For clinically employed antidepressants, we carried out a meta-analytic review of placebo-controlled trials in acute, unipolar, major depressive episodes reported over the past three decades to compare efficacy (drug-placebo RDs) of individual antidepressants and classes, and to consider factors associated with year-of-reporting by bivariate and multivariate regression modeling. Observed drug-placebo differences were moderate and generally similar among specific drugs, but larger among older antidepressants, notably tricyclics, than most newer agents. This outcome parallels selective increases in placebo-associated responses as trial-size has increased in recent years. Study findings generally support moderate efficacy of clinically employed antidepressants for acute major depression, but underscore limitations of meta-analyses of controlled trials for ranking drugs by efficacy. We suggest that efficiency and drug-placebo differences may be improved with fewer sites and subjects, and better quality-control of diagnostic and clinical assessments.
抗抑郁药 - 安慰剂反应差异（RDs）在对照试验中一直在下降，这可能会混淆对新旧药物的比较。对于临床上使用的抗抑郁药，我们对过去三十年中报告的急性、单相、重度抑郁症的安慰剂对照试验进行了荟萃分析审查，以比较个别抗抑郁药和类别的疗效（药物 - 安慰剂 RDs），并考虑与报告年份相关的因素，采用双变量和多变量回归模型进行分析。观察到的药物 - 安慰剂差异在特定药物之间是中等的，并且大致相似，但在较旧的抗抑郁药（尤其是三环类抗抑郁药）中比大多数较新的药物更大。这一结果与近年来随着试验规模的增加，安慰剂相关反应的选择性增加相一致。研究结果普遍支持临床上使用的抗抑郁药对急性重度抑郁症的中等疗效，但强调了对照试验荟萃分析对药物疗效排名的局限性。我们建议，通过减少试验点和试验对象数量，并更好地控制诊断和临床评估的质量控制，可以提高效率和药物 - 安慰剂差异。
