Placebo's Invisible Brother: a Restricted Scoping Review of the Biomedical Literature on the Nocebo Effect

Placebos and their beneficial clinical and psychological effects are well-researched, but nocebo effects receive far less attention, despite being highly undesirable. The aim of this restricted scoping review was to examine how nocebo effects are represented in the biomedical literature and to identify the trends and gaps in existing knowledge. After searching 5 biomedical databases and 2 clinical trials registries (from their inception to December 23, 2020) for articles on nocebo effects or negative placebo effects, 1161 eligible publications were identified. The 2 main publication types were nonsystematic reviews (37.7%) and primary research studies (35.6%); only 85 publications (7.3%) were systematic reviews and meta-analyses. The nonsystematic reviews, many of them heavily opinion-based, may contribute to the amplification of narratives, attitudes, and beliefs about nocebo effects that do not objectively reflect the primary research. The primary research articles often used nocebo effects to explain results, rather than as the primary phenomenon under investigation. Most publications were concerned with both positive and negative placebo effects, rather than just nocebo effects. Over half of the abstracts were in the field of neurology, psychiatry, psychology, or neuroscience (52.8%). The nocebo effect was most frequently investigated in the context of pain. Studies were almost exclusively in adults and more often in healthy participants than in patients. In conclusion, in the biomedical literature, there is an overabundance of nonsystematic reviews and expert opinions and a lack of primary research and high-quality systematic reviews and meta-analyses specifically dealing with nocebo effects.