Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 Munich, Germany.
Paris Descartes University, INSERM, UMR1153 Epidemiology and Statistics, Sorbonne Paris Cité Research Center (CRESS), METHODS Team; Cochrane France, Paris, France.
Schizophr Res. 2018 Nov;201:315-323. doi: 10.1016/j.schres.2018.05.009. Epub 2018 May 24.
A recent meta-regression had shown that the degree of placebo response, which has increased over the decades, is the major predictor of drug-placebo differences in antipsychotic drug trials in acutely ill patients with schizophrenia. Drug response, however, had remained stable. In the current meta-regression we explored the factors that are associated with placebo-response.
We searched multiple electronic databases, ClinicalTrials.gov and the FDA website for randomized, placebo-controlled, antipsychotic drug trials in patients with acute exacerbations of schizophrenia. The outcome was the degree of placebo response measured by the BPRS or PANSS change from baseline to endpoint. 26 patient-, design-, and drug-related potential predictors of placebo response were analyzed by univariable and multivariable meta-regressions.
167 double-blind randomized controlled trials with 28,102 participants were included. The mean PANSS change from baseline was 6.25 (95% CI 4.64,7.85). More recent publication year, larger study sample size, more study sites, use of the PANSS rather than the BPRS scale to measure response, shorter wash-out phases, shorter study duration, lower mean age and shorter duration of illness were associated with larger placebo response in univariable analyses. In a multivariable analysis only the number of study participants and mean participant age had an impact on placebo response.
The degree of placebo response is moderated by a number of design and patient-related factors. These explanatory variables of placebo response are only in part identical with those that moderated drug-placebo differences.
最近的一项荟萃回归分析表明，安慰剂反应程度在过去几十年中有所增加，是精神分裂症急性发作患者抗精神病药物试验中药物-安慰剂差异的主要预测因素。然而，药物反应一直保持稳定。在当前的荟萃回归分析中，我们探讨了与安慰剂反应相关的因素。
我们搜索了多个电子数据库、ClinicalTrials.gov 和 FDA 网站，以寻找针对急性恶化的精神分裂症患者的随机、安慰剂对照、抗精神病药物试验。结果是用 BPRS 或 PANSS 从基线到终点的变化来衡量的安慰剂反应程度。通过单变量和多变量荟萃回归分析了 26 个与患者、设计和药物相关的潜在安慰剂反应预测因素。
共纳入 167 项双盲随机对照试验，涉及 28102 名参与者。基线时 PANSS 的平均变化为 6.25（95%CI 4.64,7.85）。更近的出版年份、更大的研究样本量、更多的研究地点、使用 PANSS 而不是 BPRS 量表来衡量反应、更短的洗脱期、更短的研究持续时间、更低的平均年龄和更短的病程与单变量分析中的更大的安慰剂反应相关。在多变量分析中，只有研究参与者的数量和平均参与者年龄对安慰剂反应有影响。
安慰剂反应的程度受到许多设计和患者相关因素的调节。这些安慰剂反应的解释变量与调节药物-安慰剂差异的变量只有部分相同。
