Waltz James A, Pujji Sherry D, Colloca Luana
Maryland Psychiatric Research Center (MPRC), Department of Psychiatry, https://ror.org/055yg0521University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Pain and Translational Symptom Science, Placebo Beyond Opinions (PBO) Center, https://ror.org/04rq5mt64University of Maryland School of Nursing, Baltimore, MD, USA.
Psychol Med. 2025 Jul 18;55:e199. doi: 10.1017/S0033291725100901.
The experience of psychosis in schizophrenia spectrum disorders involves significant distress and functional impairment, contributing to immense social and economic costs. Current gold standard treatment guidelines emphasize the use of antipsychotic medications, though responses to these treatments vary widely, with the potential for detrimental side effects. However, increasing placebo responses in randomized controlled trials since the 1960s complicate the development of new medications. Elevated placebo responses are common in psychiatric populations, including those with psychosis, and are influenced by individual beliefs and prior experiences. Despite extensive research on placebo mechanisms in conditions such as depression and pain, little is known about mechanisms of these effects in psychosis. This narrative review examines the predictors and belief formation processes underlying placebo and nocebo phenomena in psychosis. We discuss features of randomized controlled trials for antipsychotic medications, individual symptom heterogeneity, and contextual factors. Findings related to placebo effects for motivation and cognition-enhancing drugs are also discussed. We then consider the possibility that theories of predictive coding and aberrant salience provide explanation for aspects of both placebo effects and schizophrenia spectrum symptoms. The role of outcome expectations broadly and in the context of reward processing is considered. We conclude with some recommendations for future placebo research in psychosis, emphasizing the diversity of placebo effects, assessment concerns, cultural considerations, and methodological aspects. Future multidisciplinary research is required to further elucidate placebo effects in schizophrenia spectrum disorders.
精神分裂症谱系障碍中的精神病体验会带来极大的痛苦和功能损害，造成巨大的社会和经济成本。当前的金标准治疗指南强调使用抗精神病药物，尽管对这些治疗的反应差异很大，且可能产生有害的副作用。然而，自20世纪60年代以来，随机对照试验中安慰剂反应的增加使新药研发变得复杂。安慰剂反应升高在包括患有精神病的人群在内的精神科群体中很常见，并且受到个体信念和既往经历的影响。尽管对抑郁症和疼痛等病症中的安慰剂机制进行了广泛研究，但对于这些效应在精神病中的机制知之甚少。这篇叙述性综述探讨了精神病中安慰剂和反安慰剂现象背后的预测因素和信念形成过程。我们讨论了抗精神病药物随机对照试验的特征、个体症状异质性和背景因素。还讨论了与动机和认知增强药物的安慰剂效应相关的研究结果。然后，我们考虑预测编码和异常显著性理论是否能为安慰剂效应和精神分裂症谱系症状的某些方面提供解释。广泛地以及在奖励处理背景下考虑结果预期的作用。我们最后对精神病未来的安慰剂研究提出了一些建议，强调安慰剂效应的多样性、评估问题、文化考量和方法学方面。未来需要多学科研究来进一步阐明精神分裂症谱系障碍中的安慰剂效应。
