Nocebo effect in refractory partial epilepsy during pre-surgical monitoring: Systematic review and meta-analysis of placebo-controlled clinical trials.

PURPOSE: Nocebo is very prevalent among neurological diseases resulting in low adherence and treatment outcome. We sought to examine the AEs following placebo administration in Randomized Controlled Studies (RCTs) for Epilepsy.

METHOD: After a systematic Medline search for RCTs for Epilepsy pharmacological treatments, we assessed the number of discontinuations because of placebo intolerance.

RESULTS: Data were extracted from 4 RCTs fulfilling our search criteria. Three out of 5 placebo-treated patients (60.8%) reported at least one AE and 4.0% discontinued placebo treatment because of AEs. All patients participating in the epilepsy RCTs reported similar AEs independently of the study arm they belonged.

CONCLUSION: Very limited epilepsy RCTs with pure placebo groups are available and all are in treatment resistant patients during pre-surgical monitoring. However, our study indicates a significant nocebo effect in trials for epilepsy treatment adversely affecting adherence and efficacy of current treatments in clinical practice, with additional implications for trial designing.