University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada; The Ottawa Hospital Research Institute, Ottawa, ON, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
Int Rev Neurobiol. 2020;153:121-146. doi: 10.1016/bs.irn.2020.04.005. Epub 2020 Jun 9.
The power of placebos is commonly associated with the placebo effect. In contrast, detrimental effects related to the use of a placebo are little studied and less well recognized. This chapter covers the nocebo and lessebo effects defined, respectively, as expectation of harm in the form of adverse events in a placebo arm and reduction of therapeutic benefit due to the uncertainty of being allocated to placebo. The lessebo effect is a more recent concept and has been described only in depression, schizophrenia and Parkinson's disease. The nocebo response was evaluated in many neurological diseases, including epilepsy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, restless leg syndrome, among others. Meta-analyses of randomized controlled trials in these conditions reveal a significant variability of the magnitude of the nocebo response and that factors related to study design, study participants or neurological disease can be associated with a nocebo response, although with the opposing findings across conditions. The knowledge about neurobiological mechanisms of the nocebo effect is poor for neurological diseases, and most of the information has been generated in pain. Functional neuroimaging suggests the existence of a distinct network for the anticipation and the experience of a hyperalgesia nocebo response. Different types of neurotransmitters have been involved, including cholecystokinin, dopamine and opioids. Recognizing the potential impact of nocebo and lessebo effects, mitigating strategies are in development with application to clinical research and clinical practice, such as a contextualized informed consent process, alternative study designs and enhancement of patient-physician communication.
安慰剂的效力通常与安慰剂效应有关。相比之下，与使用安慰剂相关的不利影响研究较少，认识也较少。本章涵盖了已定义的反安慰剂和减效安慰剂效应，分别是指在安慰剂组中出现不良事件的预期伤害和由于分配到安慰剂而对治疗效果产生的不确定性导致的治疗效果降低。减效安慰剂效应是一个较新的概念，仅在抑郁症、精神分裂症和帕金森病中有所描述。反安慰剂反应在许多神经疾病中进行了评估，包括癫痫、多发性硬化症、帕金森病、阿尔茨海默病、不宁腿综合征等。这些疾病的随机对照试验的荟萃分析显示，反安慰剂反应的幅度存在很大的可变性，与研究设计、研究参与者或神经疾病相关的因素可能与反安慰剂反应有关，但在不同疾病中存在相反的发现。对于神经疾病，关于反安慰剂效应的神经生物学机制的知识很少，大部分信息都是在疼痛中产生的。功能神经影像学表明，存在一个用于预期和体验痛觉过敏反安慰剂反应的独特网络。已涉及到不同类型的神经递质，包括胆囊收缩素、多巴胺和阿片类药物。认识到反安慰剂和减效安慰剂效应的潜在影响，正在制定缓解策略，应用于临床研究和临床实践，例如上下文知情同意过程、替代研究设计和增强医患沟通。
