The Influence of Side Effects on the Nocebo and Placebo Response

Abstract

Previous research has shown that experiencing side effects is potentially a strong predictor of a medications’ perceived efficacy. This is likely due to the fact that side effects increase individuals’ expectations that the medicine is, or is not, working. The personal and clinical contexts in which side effects develop are crucial determining factors of a positive or negative response to treatment. This study aimed to investigate to what extent the frequency of side effects reported influences the perceived efficacy of a medication. Additionally, the study investigated the role of anxiety and perceived sensitivity to medicines (PSM) on symptom reporting and the attribution of non-specific symptoms as side effects after a treatment. Eighty participants were recruited for a study purportedly investigating the influence of a bronchodilator medication to improve memory performance. Participants were randomly allocated to receive an inert placebo, or low, medium, or high strength active placebos. The placebos contained various strengths of capsaicin in sesame oil as the active ingredient. Analysis revealed the strength of active placebo did not influence the perceived efficacy of the medication. No dose-response effects were found for perceived efficacy of the medication for improving memory performance or subjective ease of breathing. A significant placebo dose-response in objective measures of lung function was observed (p = .049) in FEV1% predicted. This result was reflected in a placebo effect for subjective ratings in ease of breathing (p = .019). High anxiety (p < .001) and high PSM (p = .047) baseline scores were associated with higher baseline symptoms. High baseline anxiety scores resulted in more symptoms at post-medication (p < .001), and more side effects attributed to the medication at 24 hour follow up than low anxiety (p = .046). High baseline PSM scores showed no difference in symptoms at post-medication, but more side effects attributed to the medication at follow up than low PSM (p = .013). This study found that the strength of an active placebo did not influence perceived efficacy of a medication. The study demonstrated the powerful effect of an active placebo to elicit physiological improvements in lung function. The study also shows how anxiety and perceived sensitivity to medications can induce expectations of nocebo side effects. The study also shows that the mechanisms through which side effects influence perceived efficacy of a medication are complex and require further investigation.