Medicine-related beliefs predict attribution of symptoms to a sham medicine: A prospective study

ObjectivesTo investigate a range of possible predictors of nocebo responses to medicines. DesignProspective cohort study. MethodsIn 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. ResultsMen 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. ConclusionIt 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. 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.