IMPACT SRC (Innovation in Mental and Physical Health and Clinical Treatment - Strategic Research Centre), School of Medicine, Deakin University, Geelong, Victoria, Australia.
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
Bipolar Disord. 2019 Mar;21(2):142-150. doi: 10.1111/bdi.12662. Epub 2018 Jun 21.
In the clinical setting, the nocebo phenomenon is where clinical worsening or adverse events occur as a response to a treatment, in a situation in which conditioning from previous treatment exposure and/or expectations of sickness or symptoms lead to sickness and symptoms in a conditioned or expectant individual. The nocebo response may thus be a confounder in clinical treatment and clinical research. There is a need to know how to predict if an individual is likely to be a nocebo responder, and how significant and commonplace the nocebo effect might be.
An analysis was conducted on nine placebo-controlled, randomized clinical trials of olanzapine for the treatment of bipolar disorder using data from placebo-treated study participants only. Data were analysed to identify participant or study characteristics associated with a nocebo event, defined as any treatment-emergent adverse event (TEAE) or an increase in score from baseline to endpoint for primary measures of clinical symptoms.
A total of 1185 participants were randomized to placebo, of whom 806 (68%) reported a TEAE. Hamilton Depression Rating Scale (HDRS) data were only available for 649 placebo-treated participants, of whom 321 (49.5%) demonstrated worsening. Nocebo events were significantly associated with: not being treatment-naïve, younger age, being located in the USA, being a participant in an earlier study, and being classified as obese compared with normal weight.
A pattern to identify nocebo responders did not emerge, although some prognostic variables were associated with a greater probability of nocebo response. There was some evidence to support the role of expectancy as a cause of nocebo reactions.
在临床环境中，当一种治疗引起临床恶化或不良反应，而先前的治疗暴露和/或对疾病或症状的预期导致条件反射或预期个体出现疾病和症状时，就会出现安慰剂效应。因此，安慰剂反应可能是临床治疗和临床研究中的一个混杂因素。需要了解如何预测个体是否可能成为安慰剂反应者，以及安慰剂效应的显著程度和常见程度。
仅使用安慰剂治疗研究参与者的数据，对九项奥氮平治疗双相情感障碍的安慰剂对照、随机临床试验进行了分析。对数据进行了分析，以确定与安慰剂反应相关的参与者或研究特征，安慰剂反应定义为任何治疗引起的不良事件（TEAE）或主要临床症状的基线至终点评分增加。
共有 1185 名参与者被随机分配至安慰剂组，其中 806 名（68%）报告了 TEAE。只有 649 名接受安慰剂治疗的参与者有汉密尔顿抑郁量表（HDRS）数据，其中 321 名（49.5%）病情恶化。安慰剂反应与以下因素显著相关：非初次治疗、年龄较小、位于美国、参加较早的研究、以及与正常体重相比被归类为肥胖。
虽然一些预后变量与更大的安慰剂反应概率相关，但没有出现识别安慰剂反应者的模式。有证据支持期望作为安慰剂反应的原因。
