title: Nocebo effect in refractory partial epilepsy during pre-surgical monitoring: Systematic review and meta-analysis of placebo-controlled clinical trials.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Academic Directorate of Neurosciences, University of Sheffield, UK; Department of Neurology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK. Electronic address: takiszis@gmail.com.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Zis
authors.affiliation: Academic Directorate of Neurosciences, University of Sheffield, UK.
authors.forename: Faiza
authors.initials: F
authors.lastname: Shafiq
authors.affiliation: Athens Naval Hospital, Neurology Department, Athens, Greece.
authors.forename: Dimos-Dimitrios
authors.initials: DD
authors.lastname: Mitsikostas
mesh_terms: D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000523:psychology* / Q000601:surgery; D006801:Humans; D016239:MEDLINE; D064786:Nocebo Effect; D011300:Preoperative Care; D016032:Randomized Controlled Trials as Topic
keywords: Adverse events; Epilepsy; Nocebo; Placebo; Trial design