Palermo Sara, Giovannelli Fabio, Bartoli Massimo, Amanzio Martina
Department of Psychology, University of Turin, Turin, Italy.
European Innovation Partnership on Active and Healthy Ageing, Brussels, Belgium.
Front Pharmacol. 2019 May 17;10:502. doi: 10.3389/fphar.2019.00502. eCollection 2019.
Antipsychotic clinical trials use to present adverse events (AEs) for the drug under evaluation to treat schizophrenia. Interestingly, patients who receive the placebo during antipsychotic trials often report several AEs, but little is known about the essence of these negative effects in patients with schizophrenia spectrum disorders (SCD). In the present meta-analysis, we evaluated the relationship between the level of psychiatric symptomatology expressed as Positive and Negative Syndrome Scale (PANSS) scores and the rates of AEs reported in the placebo arms of double-blind clinical trials, for commonly prescribed atypical antipsychotic medications. We selected 58 clinical trials describing AEs in SCD placebo groups, which compared atypical antipsychotic medications with placebo. A total of 6,301 placebo-treated patients were considered. AE profiles of the class were clusterized using MedDRA classification and analysed using a meta-regression approach. In the placebo arms the proportions of patients with any AE was 66.3% (95% CI: 62.7-69.8%). The proportion of withdrawal of patients treated with placebo because of AEs was 7.2% (95% CI: 5.9-8.4%). Interestingly, the AEs in the placebo arms corresponded to those of the antipsychotic-atypical-medication-class against which the placebo was compared. Namely, using meta-regression analysis we found an association between the level of psychiatric symptomatology measured with PANSS scores and higher AEs reported as nervous system ( = 0.020) and gastrintestinal disorders ( = 0.004). Moreover, the level of a higher psychiatric symptomatology expressed with PANSS scores was also related with higher AEs associated with psychiatric symptoms ( = 0.017). These findings emphasise that the AEs in placebo arms of clinical trials of antipsychotic medications were substantial. Importantly, a higher level of psychiatric symptomatology makes SCD patients more prone to express AEs, thus contributing to possible drop-outs and to a lower adherence to treatments. These results are consistent with the expectation theory of placebo and nocebo effects.
抗精神病药物临床试验过去常常呈现所评估药物治疗精神分裂症的不良事件（AE）。有趣的是，在抗精神病药物试验中接受安慰剂的患者经常报告多种不良事件，但对于精神分裂症谱系障碍（SCD）患者这些负面影响的本质知之甚少。在本荟萃分析中，我们评估了以阳性和阴性症状量表（PANSS）评分表示的精神症状水平与双盲临床试验安慰剂组中报告的不良事件发生率之间的关系，这些试验针对的是常用的非典型抗精神病药物。我们选择了58项描述SCD安慰剂组不良事件的临床试验，这些试验将非典型抗精神病药物与安慰剂进行了比较。总共纳入了6301名接受安慰剂治疗的患者。使用MedDRA分类对该类药物的不良事件概况进行聚类，并采用荟萃回归方法进行分析。在安慰剂组中，发生任何不良事件的患者比例为66.3%（95%置信区间：62.7 - 69.8%）。因不良事件而停用安慰剂治疗的患者比例为7.2%（95%置信区间：5.9 - 8.4%）。有趣的是，安慰剂组中的不良事件与所比较的非典型抗精神病药物类别的不良事件相对应。也就是说，通过荟萃回归分析，我们发现用PANSS评分衡量的精神症状水平与报告为神经系统不良事件（P = 0.020）和胃肠道疾病（P = 0.004）之间存在关联。此外，用PANSS评分表示的较高精神症状水平也与与精神症状相关的较高不良事件有关（P = 0.017）。这些发现强调抗精神病药物临床试验安慰剂组中的不良事件相当可观。重要的是，较高水平的精神症状使SCD患者更容易出现不良事件，从而可能导致停药和治疗依从性降低。这些结果与安慰剂和反安慰剂效应的期望理论一致。
