Zaccara Gaetano, Giovannelli Fabio, Schmidt Dieter
Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy; Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Firenze, Italy.
Epilepsy Behav. 2015 Feb;43:128-34. doi: 10.1016/j.yebeh.2014.12.004. Epub 2015 Feb 19.
Placebo response can be defined as any therapeutic change on placebo, while the nocebo response is any ill effect during placebo exposure. Several meta-analytic approaches have investigated the extent of placebo response in randomized, placebo-controlled, clinical trials of focal epilepsies. Placebo response rates (proportion of patients with ≥50% improvement of seizures versus baseline) ranging from 9.9% up to 15.2% have been reported. Interestingly, a sham response of 15.8% has been noted in trials of transcranial magnetic stimulation. Recently, nocebo response rates of 60.3% and 3.9% were noted, which were defined as the proportion of patients with adverse events (AEs) and those withdrawing because of intolerable AEs, respectively. Factors which were found to influence placebo response were as follows: the year of publication (with more recent studies showing higher rates of placebo response), some clinical characteristics of recruited patients (lower placebo response rates with a history of 7 or more prior lifetime AEDs, a high baseline seizure frequency, prior epilepsy surgery, and higher age at diagnosis), trial design and statistical analysis, and whether studies have been conducted in children or adults. Furthermore, placebo and nocebo rates were correlated with respective seizure outcome and adverse events of the experimental AED. Several mechanisms of placebo and nocebo responses are discussed. Specifically, the role of positive or negative expectations of patients and of investigators may influence the placebo and the nocebo response. Finally, recommendations are given on how to address placebo and nocebo responses in clinical practice.
安慰剂反应可定义为服用安慰剂后的任何治疗性变化，而反安慰剂反应则是指在服用安慰剂期间出现的任何不良影响。几种荟萃分析方法已在局灶性癫痫的随机、安慰剂对照临床试验中研究了安慰剂反应的程度。据报道，安慰剂反应率（与基线相比癫痫发作改善≥50%的患者比例）在9.9%至15.2%之间。有趣的是，在经颅磁刺激试验中发现了15.8%的假反应。最近，反安慰剂反应率分别为60.3%和3.9%，分别定义为出现不良事件（AE）的患者比例和因无法耐受AE而退出的患者比例。发现影响安慰剂反应的因素如下：发表年份（近期研究显示安慰剂反应率更高）、招募患者的一些临床特征（有7次或更多既往终身抗癫痫药物治疗史、基线癫痫发作频率高、既往癫痫手术史以及诊断时年龄较大的患者安慰剂反应率较低）、试验设计和统计分析，以及研究是在儿童还是成人中进行。此外，安慰剂和反安慰剂率与实验性抗癫痫药物各自的癫痫发作结果和不良事件相关。文中讨论了安慰剂和反安慰剂反应的几种机制。具体而言，患者和研究者的积极或消极期望可能会影响安慰剂和反安慰剂反应。最后，针对如何在临床实践中应对安慰剂和反安慰剂反应给出了建议。
