title: Do antiepileptic drugs increase the risk of infectious diseases? A meta-analysis of placebo-controlled studies.
abstract: OBJECTIVE
  Experimental studies show that some antiepileptic drugs (AEDs) may modify natural immune defences, thus influencing the risk of developing infectious diseases. The aim of this meta-analysis was to explore whether AEDs as a class of drugs or singularly may increase risk of infectious diseases.
  
  
  METHODS
  A meta-analysis of all randomized, double-blind, placebo-controlled trials (RCTs) investigating any AED in any condition was performed. All terms that could be coded in the System Organ Classes (SOCs) of infections and infestations using the Medical Dictionary for Regulatory Activities were recorded. Additional subanalyses were performed also pooling together AEDs sharing similar mechanisms of action.
  
  
  RESULTS
  Two hundreds and sixty-nine double-blind, placebo-controlled studies were identified and, among them, 127 RCTs with 16 AEDs (brivaracetam, gabapentin, lacosamide, levetiracetam, lamotrigine, oxcarbazepine, perampanel, pregabalin, phenytoin, remacemide, retigabine, rufinamide, tiagabine, topiramate, valproate, zonisamide) reported at least one of 19 symptoms or diseases that could be included in the Medical Dictionary for Regulatory Activities SOC term infections and infestations. These terms were singularly recorded and then pooled together in the SOC term infection and infestation. Topiramate was significantly associated with an increased risk of infection (risk difference = 0.04; 95% confidence interval = 0.01/0.06), while oxcarbazepine was significantly associated with a lower risk (-0.005; -0.09/-0.01). Risk difference of all studies with all AEDs showed a slight, but significantly increased risk of infection (0.01; 0.00/0.002). Levetiracetam and brivaracetam RCTs, when pooled together, were associated with a significantly increased risk of infection (0.03; 0.01/0.05).
  
  
  CONCLUSIONS
  Some AEDs are associated with a mild increased risk of infection.
authors.affiliation: Unit of Neurology, Department of Medicine, Florence Health Authority, Florence, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zaccara
authors.affiliation: Unit of Neurology, Department of Medicine, Florence Health Authority, 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: Department of Clinical and Experimental Medicine, Section of Neurology, University of Pisa and Pisa University Hospital, Pisa, Italy.
authors.forename: Filippo Sean
authors.initials: FS
authors.lastname: Giorgi
authors.affiliation: Department of Internal Medicine and Therapeutics, Division of Clinical and Experimental Pharmacology, University of Pavia, 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
authors.affiliation: Pharmacovigilance Centre, Florence Health Authority, Florence, Italy.
authors.forename: Francesco Mandò
authors.initials: FM
authors.lastname: Tacconi
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D003141:Communicable Diseases / Q000139:chemically induced*; D006801:Humans
chemical_list: D000927:Anticonvulsants
keywords: adverse effects; antiepileptic drugs; infection; medDRA; meta-analysis