A scoping review of placebo and nocebo responses and effects: insights for clinical trials and practice

Placebo and nocebo responses and effects influence treatment outcomes across a variety of conditions. The current scoping review aims to synthesise evidence from systematic reviews and meta-analyses in both clinical and healthy populations, elucidating key determinants of placebo and nocebo responses and effects, including individual, clinical, psychological and contextual factors. Among the 306 publications identified, 83% were meta-analyses and 17% systematic reviews, with a predominance of research in medical specialties (81.7%) such as psychiatry and neurology. Placebo responses were significantly more studied than nocebo responses. Individual determinants (e.g., age), clinical determinants (e.g., baseline symptom severity) and psychological determinants (e.g., expectations) were found to influence placebo and nocebo outcomes. Contextual determinants, including trial design and the method of treatment administration, also played critical roles. Several key underinvestigated areas in the current body of systematic reviews and meta-analyses were also identified. This scoping review highlights valuable insights into the determinants of placebo and nocebo responses and effects on a group level, potentially offering practical implications for optimising clinical trial designs and enhancing patient care strategies in clinical practice. However, to fully leverage these benefits, it is crucial to address the underexplored topics through more rigorous investigations using a person-centred perspective.