Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
Department of Nursing. Faculty of Health Sciences, University of Granada, Granada, Spain.
Eur J Clin Invest. 2022 Jul;52(7):e13762. doi: 10.1111/eci.13762. Epub 2022 Feb 27.
Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This meta-analysis assessed whether placebo conditions (active controls) had an effect compared to no treatment or usual care (passive controls).
PubMed, Scopus, PsycINFO, PsycARTICLES, Ovid, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to April 2021 and reference lists of relevant articles. Three-arm RCTs, including active and passive control groups, were selected. Where individual standardized mean difference (SMD) was calculable, random effects meta-analyses were performed to estimate an overall effect size with 95% confidence intervals (CI) comparing active vs passive controls. Heterogeneity was assessed using I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test (Prospero registration: CRD42021242940).
24 articles with 25 relevant RCTs were included in the review, of which 11 studies were of high risk of bias. There was an improvement in outcomes favouring the placebo conditions, compared to passive controls, overall (25 studies, SMD 0.24, 95% CI 0.06-0.42, I² = 43%) and in subgroups with anxiety (SMD 0.45, 95% CI 0.07-0.84, I² = 59%) or depression (SMD 0.22, 95% CI 0.04-0.39, I² = 0%). Meta-regression did not show a significant explanation for heterogeneity. Egger's test showed no asymmetry (p = .200).
A small placebo effect was observed in mental disorders research overall, and in patients with anxiety or depression. These findings should be interpreted with caution in the light of heterogeneity and risk of bias.
精神障碍研究中的随机对照试验（RCT）通常使用包括心理治疗模拟或无效药物在内的活性对照。本荟萃分析评估了安慰剂条件（活性对照）与无治疗或常规护理（被动对照）相比是否具有疗效。
从成立到 2021 年 4 月，我们在 PubMed、Scopus、PsycINFO、PsycARTICLES、Ovid、Cochrane 对照试验中心注册库和 Web of Science 上进行了检索，并查阅了相关文章的参考文献列表。选择了包括活性和被动对照组的三臂 RCT。在可以计算个体标准化均数差值（SMD）的情况下，采用随机效应荟萃分析来估计活性与被动对照相比的总体效应大小，并计算 95%置信区间（CI）。使用 I²统计量和 meta 回归评估异质性。采用 Egger 检验（Prospero 注册：CRD42021242940）评估漏斗图不对称性。
综述共纳入 24 篇文章中的 25 项相关 RCT，其中 11 项研究存在较高的偏倚风险。与被动对照相比，安慰剂条件总体上（25 项研究，SMD 0.24，95%CI 0.06-0.42，I²=43%）和在焦虑（SMD 0.45，95%CI 0.07-0.84，I²=59%）或抑郁（SMD 0.22，95%CI 0.04-0.39，I²=0%）患者亚组中，结局均有改善。meta 回归未显示异质性的显著解释。Egger 检验未显示不对称性（p=0.200）。
总体而言，在精神障碍研究中观察到了较小的安慰剂效应，在焦虑或抑郁患者中也观察到了这种效应。鉴于异质性和偏倚风险，这些发现应谨慎解释。
