title: Inverse Association between Sodium Channel-Blocking Antiepileptic Drug Use and Cancer: Data Mining of Spontaneous Reporting and Claims Databases.
abstract: OBJECTIVE
  Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. Recently, a decreased risk of cancer associated with sodium channel-blocking antiepileptic drugs (AEDs) has become a research focus of interest. The purpose of this study was to test the hypothesis that the use of sodium channel-blocking AEDs are inversely associated with cancer, using different methodologies, algorithms, and databases.
  
  
  METHODS
  A total of 65,146,507 drug-reaction pairs from the first quarter of 2004 through the end of 2013 were downloaded from the US Food and Drug Administration Adverse Event Reporting System. The reporting odds ratio (ROR) and information component (IC) were used to detect an inverse association between AEDs and cancer. Upper limits of the 95% confidence interval (CI) of < 1 and < 0 for the ROR and IC, respectively, signified inverse associations. Furthermore, using a claims database, which contains 3 million insured persons, an event sequence symmetry analysis (ESSA) was performed to identify an inverse association between AEDs and cancer over the period of January 2005 to May 2014. The upper limit of the 95% CI of adjusted sequence ratio (ASR) < 1 signified an inverse association.
  
  
  RESULTS
  In the FAERS database analyses, significant inverse associations were found between sodium channel-blocking AEDs and individual cancers. In the claims database analyses, sodium channel-blocking AED use was inversely associated with diagnoses of colorectal cancer, lung cancer, gastric cancer, and hematological malignancies, with ASRs of 0.72 (95% CI: 0.60 - 0.86), 0.65 (0.51 - 0.81), 0.80 (0.65 - 0.98), and 0.50 (0.37 - 0.66), respectively. Positive associations between sodium channel-blocking AEDs and cancer were not found in the study.
  
  
  CONCLUSIONS
  Multi-methodological approaches using different methodologies, algorithms, and databases suggest that sodium channel-blocking AED use is inversely associated with colorectal cancer, lung cancer, gastric cancer, and hematological malignancies.
authors.affiliation: Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Takada
authors.affiliation: Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Motomura
authors.affiliation: Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hosomi
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D057225:Data Mining; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000453:epidemiology*; D026941:Sodium Channel Blockers / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000927:Anticonvulsants; D026941:Sodium Channel Blockers
keywords: Voltage-gated sodium channels
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