Department of Psychology, University of Turin, Via Verdi 10, 10123 Turin, Italy Neuroscience Institute of Turin (NIT), University of Turin, Italy Department of Psychology, University of Aarhus, Jens Chr. Skous Vej 4, DK - 8000 Århus C, Denmark Department of Neuroscience, University of Turin Medical School, Corso Raffaello 30, 10125 Turin, Italy National Institute of Neuroscience (INN), Turin, Italy.
Pain. 2009 Dec;146(3):261-269. doi: 10.1016/j.pain.2009.07.010. Epub 2009 Sep 24.
In analgesic clinical trials, adverse events are reported for the painkiller under evaluation and compared with adverse events in the placebo group. Interestingly, patients who receive the placebo often report a high frequency of adverse events, but little is understood about the nature of these negative effects. In the present study, we compared the rates of adverse events reported in the placebo arms of clinical trials for three classes of anti-migraine drugs: NSAIDs, triptans and anticonvulsants. We identified 73 clinical trials in 69 studies describing adverse events in placebo groups: 8 were clinical trials with NSAIDs, 56 were trials with triptans, and 9 were trials with anticonvulsants. Studies were selected of all Medline/PubMed or CENTRAL referenced trials published until 2007. Adverse event profiles of the three classes were compared using a systematic review approach. We found that the rate of adverse events in the placebo arms of trials with anti-migraine drugs was high. In addition, and most interestingly, the adverse events in the placebo arms corresponded to those of the anti-migraine medication against which the placebo was compared. For example, anorexia and memory difficulties, which are typical adverse events of anticonvulsants, were present only in the placebo arm of these trials. These results suggest that the adverse events in placebo arms of clinical trials of anti-migraine medications depend on the adverse events of the active medication against which the placebo is compared. These findings are in accordance with the expectation theory of placebo and nocebo effects.
在镇痛临床试验中，评估的止痛药的不良事件与安慰剂组的不良事件进行比较。有趣的是，接受安慰剂的患者经常报告不良事件的高频率，但对这些负面影响的性质知之甚少。在本研究中，我们比较了三类抗偏头痛药物（非甾体抗炎药、曲坦类和抗惊厥药）安慰剂组报告的不良事件发生率。我们确定了 69 项研究中的 73 项临床试验，描述了安慰剂组的不良事件：8 项是 NSAIDs 的临床试验，56 项是曲坦类的临床试验，9 项是抗惊厥药的临床试验。选择了所有截止到 2007 年在 Medline/PubMed 或 CENTRAL 上发表的参考试验。使用系统评价方法比较了这三类的不良事件概况。我们发现，抗偏头痛药物试验安慰剂组的不良事件发生率很高。此外，最有趣的是，安慰剂组的不良事件与对照的抗偏头痛药物的不良事件相对应。例如，厌食和记忆困难，这是抗惊厥药的典型不良事件，仅出现在这些试验的安慰剂组中。这些结果表明，抗偏头痛药物临床试验安慰剂组的不良事件取决于与安慰剂进行比较的活性药物的不良事件。这些发现与安慰剂和无安慰剂效应的期望理论一致。
