title: Analysis of nocebo effects of antiepileptic drugs across different conditions.
abstract: The aim of this study was to assess the nocebo effect in all randomised controlled trials (RCTs) exploring the effect of antiepileptic drugs (AEDs) in the clinical conditions in which these compounds have been studied with the exception of epilepsy. We searched for all double-blind, placebo-controlled trials performed in adult patients, testing AEDs in any clinical condition except epilepsy. The following data were extracted from the placebo arms: the number of randomized patients, the number of patients withdrawing because of adverse effects (AEs), and the number of patients with 11 predefined AEs (dizziness, ataxia/coordination abnormal, diplopia, somnolence, fatigue, headache, memory impairment, tremor, abnormal thinking, anxiety and depression). Outcome measures were the percentages of patients whithdrawing due to AEs and reporting the selected AEs. RCTs included in the analysis were grouped in six main categories of clinical conditions (pain, movement disorders, psychiatric disorders, substance abuse, obesity and binge eating disorders, and miscellanea). Proportions of patients with 95 % confidence intervals (CIs) have been calculated for all reported outcome measures. Thirteen AEDs were studied and the total number of selected RCTs was 157. Significant percentages of placebo-treated patients withdrawing due to AEs and with specific AEs were observed in several cases. Significant differences emerged across different conditions. Comparisons with results of a previous meta-analysis on all RCTs in patients with drug-resistant epilepsies showed that ataxia, diplopia and fatigue were significantly more frequent, and patients withdrawing were significantly less frequent, in placebo-treated epileptic patients. Significant differences have been identified in the AEDs-induced nocebo effect across different conditions. Placebo-treated epilepsy patients have significantly more frequent neurological AEs.
authors.affiliation: Unit of Neurology, San Giovanni di Dio Hospital, Department of Medicine, Florence Health Authority, Via Di Torregalli n 3, 50143, Florence, Italy. gaetano.zaccara@uslcentro.toscana.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zaccara
authors.affiliation: Unit of Neurology, San Giovanni di Dio Hospital, Department of Medicine, Florence Health Authority, Via Di Torregalli n 3, 50143, Florence, Italy.|Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giovannelli
authors.affiliation: Section of Neurology, Department of Clinical and Experimental Medicine, University of Pisa and Pisa University Hospital, Pisa, Italy.
authors.forename: Filippo Sean
authors.initials: FS
authors.lastname: Giorgi
authors.affiliation: C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Franco
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gasparini
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D064786:Nocebo Effect; D016032:Randomized Controlled Trials as Topic
chemical_list: D000927:Anticonvulsants
keywords: Adverse effects; Antiepileptic drugs; Meta-analysis; Nocebo effects; Placebo effects
references.citation: Rev Med Suisse. 2015 Apr 22;11(471):927-30
references.pmid: 26072600
references.citation: Neurology. 2004 Jan 13;62(1):23-7
references.pmid: 14718691
references.citation: Psychiatry Res. 2014 Jan 30;215(1):82-6
references.pmid: 24210741
references.citation: J Headache Pain. 2014 Nov 04;15:70
references.pmid: 25366245
references.citation: Mymensingh Med J. 2012 Apr;21(2):251-8
references.pmid: 22561767
references.citation: Pharmacol Ther. 2013 Dec;140(3):306-18
references.pmid: 23880289
references.citation: CNS Drugs. 2005;19(11):897-908
references.pmid: 16268662
references.citation: Lancet. 2010 Feb 20;375(9715):686-95
references.pmid: 20171404
references.citation: Lancet Neurol. 2012 Sep;11(9):792-802
references.pmid: 22832500
references.citation: BMJ. 2015 Sep 04;351:h4672
references.pmid: 26341898
references.citation: Epilepsia. 1998 Feb;39(2):213-31
references.pmid: 9578003
references.citation: Dtsch Arztebl Int. 2012 Jun;109(26):459-65
references.pmid: 22833756
references.citation: Epilepsy Behav. 2015 Feb;43:128-34
references.pmid: 25703333
references.citation: J Neurol. 2015 Mar;262(3):501-15
references.pmid: 24916828
references.citation: Ecancermedicalscience. 2013 Sep 04;7:346
references.pmid: 24019848
references.citation: Philos Trans R Soc Lond B Biol Sci. 2011 Jun 27;366(1572):1889-95
references.pmid: 21576146
references.citation: Eur J Neurol. 2013 Mar;20(3):527-33
references.pmid: 23145482
references.citation: EMBO Rep. 2010 Aug;11(8):572-8
references.pmid: 20634806
references.citation: BMC Med Res Methodol. 2009 Dec 04;9:80
references.pmid: 19961608
references.citation: Pain. 2009 Dec;146(3):261-9
references.pmid: 19781854
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000097
references.pmid: 19621072