Lessons learned from nocebo effects in clinical trials for pain conditions and neurodegenerative disorders

It has been demonstrated that patients in the placebo arm of a clinical trial may experience adverse events (AEs), which may lead to nonadherence and dropout. However, so far, it is unknown to which extent this phenomenon is observed consistently across different diseases such as pain and neurodegenerative disorders. The current review shows for the first time that different diseases share a common risk for patients in terms of a negative outcome: a large percentage of placebo-treated patients experience AEs in pain conditions (up to 59%) and neurodegenerative disorders (up to 66%). In addition, the rate of patients who discontinue because of AEs is up to 10% and 11% in pain conditions and neurodegenerative disorders, respectively. We highlight methodological shortcomings with the aim of suggesting how the detection and reporting of AEs can be improved in future trials. The insights from the current review should be taken into consideration when designing clinical trials to tailor individualized treatments