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Analysis of nocebo effects of antiepileptic drugs across different conditions

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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.

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Authors and Affiliations

  1. Unit of Neurology, San Giovanni di Dio Hospital, Department of Medicine, Florence Health Authority, Via Di Torregalli n 3, 50143, Florence, Italy

    Gaetano Zaccara & Fabio Giovannelli

  2. Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy

    Fabio Giovannelli

  3. Section of Neurology, Department of Clinical and Experimental Medicine, University of Pisa and Pisa University Hospital, Pisa, Italy

    Filippo Sean Giorgi

  4. C. Mondino National Neurological Institute, Pavia, Italy

    Valentina Franco

  5. Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy

    Sara Gasparini

Authors
  1. Gaetano Zaccara
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  2. Fabio Giovannelli
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  3. Filippo Sean Giorgi
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  4. Valentina Franco
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  5. Sara Gasparini
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Corresponding author

Correspondence to Gaetano Zaccara.

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Ethical publication statement

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Funding

The authors received no funding for this study. FG is supported by a grant by “Ente Cassa di Risparmio di Firenze”.

Conflicts of interest

GZ has received speaker’s or consultancy fees from EISAI, Jansen-Cilag, Sanofi-Aventis, and UCB Pharma. FG FSG and SG report no disclosures. VF is a former employee of Eisai s.r.l., Italy.

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Zaccara, G., Giovannelli, F., Giorgi, F.S. et al. Analysis of nocebo effects of antiepileptic drugs across different conditions. J Neurol 263, 1274–1279 (2016). https://doi.org/10.1007/s00415-015-8018-7

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  • DOI: https://doi.org/10.1007/s00415-015-8018-7

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