Stolk Pieter, Ten Berg Maarten J, Hemels Michiel E H, Einarson Thomas R
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, Netherlands.
Ann Pharmacother. 2003 Dec;37(12):1891-9. doi: 10.1345/aph.1D172.
Placebo effects in major depressive disorder (MDD) have received much interest in the medical literature. However, few quantitative analyses have been done in homogeneous populations.
To determine efficacy rates for placebo in patients with MDD; to quantify the correlation between efficacy and publication year, as well as between placebo and drug response rates.
Searching MEDLINE (1966-December 2000), EMBASE (1998-February 2001), HealthSTAR (1975-December 2000), and Cochrane (1980-December 2000) databases, randomized, placebo-controlled trials were retrieved including patients with MDD as defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd and 4th editions criteria, Hamilton Rating Scale for Depression score >/=18 or Montgomery-Asberg Depression Rating Scale score >/=16, reporting successes as 50% decreases in scores after 6-8 weeks of treatment. Response rates were summarized using a random effects meta-analysis for per protocol (PP) and intent-to-treat (ITT) results.
We included 24 of 134 potential studies examining 4459 patients, 1786 on placebo and 2673 on an antidepressant. Placebo response rates were 45.5% (PP) and 26.9% (ITT). Correlations were significant between year and rates (PP rho 0.448, p = 0.042; ITT rho 0.557; p = 0.006), but not for active drugs. Placebo and drug rates were correlated (PP r 0.397, p = 0.020; ITT r 0.539; p = 0.002).
These placebo rates confirm those reported previously, but were from a homogeneous population. Although statistically significant, the correlation between drug and placebo rates was lower than others reported. During the study period, placebo rates increased linearly; active drugs did not. Correlations between placebo and drug response rates reflected moderate to strong effect sizes. We suggest that current methodology has been unsuccessful in achieving unbiased double-blind conditions not influenced by extra-trial factors, including time.
医学文献中对重度抑郁症（MDD）的安慰剂效应颇感兴趣。然而，针对同质人群进行的定量分析较少。
确定MDD患者中安慰剂的有效率；量化有效率与发表年份之间的相关性，以及安慰剂与药物有效率之间的相关性。
检索MEDLINE（1966年 - 2000年12月）、EMBASE（1998年 - 2001年2月）、HealthSTAR（1975年 - 2000年12月）和Cochrane（1980年 - 2000年12月）数据库，检索随机、安慰剂对照试验，纳入符合《精神疾病诊断与统计手册》第3版和第4版标准定义的MDD患者，汉密尔顿抑郁量表评分≥18或蒙哥马利 - 阿斯伯格抑郁量表评分≥16，报告治疗6 - 8周后评分降低50%为成功。使用随机效应荟萃分析总结按方案（PP）和意向性分析（ITT）结果的有效率。
在134项潜在研究中的24项研究纳入了4459例患者，其中1786例接受安慰剂治疗，2673例接受抗抑郁药治疗。安慰剂有效率为45.5%（PP）和26.9%（ITT）。年份与有效率之间存在显著相关性（PP相关系数0.448，p = 0.042；ITT相关系数0.557，p = 0.006），但活性药物不存在这种相关性。安慰剂和药物有效率存在相关性（PP相关系数r 0.397，p = 0.020；ITT相关系数r 0.539，p = 0.002）。
这些安慰剂有效率证实了先前报道的结果，但此次研究对象为同质人群。尽管具有统计学显著性，但药物与安慰剂有效率之间的相关性低于其他报道。在研究期间，安慰剂有效率呈线性上升；活性药物则不然。安慰剂与药物有效率之间的相关性反映出中等至较强的效应量。我们认为，当前的方法未能成功实现不受试验外因素（包括时间）影响的无偏双盲条件。
