Knowledge of the aetiology and cost of the nocebo effect is increasing,but conceptualising expectancy and partialling out misattribution remain challenges: Comment on Faasse (2019)

The nocebo effect is a concerning phenomenon in which adverse outcomes are triggered by the treatment context. Faasse (2019) summarises recent evidence on mechanisms of the nocebo effect, proposes an updated model, and describes emerging techniques for reducing the nocebo effect. Faasse's model marks an important advance over prior models focussing only on expectancy and classical conditioning by incorporating the role of anxiety, which emerging evidence indicates can mediate the nocebo effect. The review also emphasises the importance of preventing the nocebo effect, given its resistance to extinction, as well as the need for translational research, both of which are timely points. However, the review also raises two challenges for nocebo research. The first concerns the conceptualisation of expectancy, with Faasse's model appearing to combine expectancy and verbal information into a single node. Such an approach suggests that verbal information necessarily and only elicits nocebo effects via expectancy, which may not hold true. The second concerns distinguishing genuine nocebo effects from misattribution. Faasse's review intentionally focuses only on the former, but it is argued that understanding the latter is necessary to accurately estimate the true cost of the nocebo effect as well as for prioritising interventions to minimise non-medication side effects. As such, in addition to Faasse's call for translational research—which I fully support—I propose that key nocebo research goals should be to understand how verbal information elicits nocebo effects outside of expectancy and to tease apart genuine nocebo effects and misattributed adverse symptoms.