ABSTRACT: OBJECTIVES:To investigate a range of possible predictors of nocebo responses to medicines. DESIGN:Prospective cohort study. METHODS:In total, 203 healthy adult volunteers completed measures concerning demographics, psychological factors, medicine-related beliefs, baseline symptoms, and symptom expectations before taking a sham pill, described as 'a well-known tablet available without prescription' that was known to be associated with several side effects. Associations between these measures and subsequent attribution of symptoms to the tablet were assessed using a hurdle model consisting of a joint logistic and truncated negative binomial regression. RESULTS:Men had an increased odds of attributing symptoms to the tablet OR = 1.52, and older participants had decreased odds, OR = 0.97. Medicine-related beliefs were important, with modern health worries, belief that medicines cause harm and perceived sensitivity to medicines associated with increased odds of symptom attribution, OR = 1.02, 1.10, 1.09, respectively. Trust in medicines and pharmaceutical companies decreased the odds of symptom attribution, OR = 0.91, 0.88, respectively. The number of symptoms at baseline and the expected likelihood of symptoms were associated with an increased odds of attributing symptoms to the tablet, OR = 1.07, 1.06, respectively. Anxiety, previous symptom experience, symptom expectations, and modern health worries were also important in predicting the number of symptoms participants attributed to the tablet. CONCLUSION:It is hard to predict who is at risk of developing nocebo responses to medicines from demographic or personality characteristics. Context-specific factors such as beliefs about and trust in medicines, current symptoms and symptom expectations are more useful as predictors. More work is needed to investigate this in a patient sample. Statement of contribution What is already known on this subject? Many patients report non-specific side effects to their medication which may arise through a nocebo effect. Whether some people are particularly predisposed to experience nocebo effects remains unclear. What does this study add? Demographic and personality characteristics are poor predictors of symptom attribution to a sham medicine. Instead, context-specific factors that concern people's beliefs surrounding medicines, their current symptoms, and symptom expectations are more useful as predictors of symptom attribution.
