PMID- 26816494
OWN - NLM
STAT- MEDLINE
DCOM- 20161021
LR  - 20220318
IS  - 1449-1907 (Electronic)
IS  - 1449-1907 (Linking)
VI  - 13
IP  - 1
DP  - 2016
TI  - Inverse Association between Sodium Channel-Blocking Antiepileptic Drug Use and 
      Cancer: Data Mining of Spontaneous Reporting and Claims Databases.
PG  - 48-59
LID - 10.7150/ijms.13834 [doi]
AB  - PURPOSE: 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. 
      CONCLUSION: 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.
FAU - Takada, Mitsutaka
AU  - Takada M
AD  - Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 
      3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
FAU - Fujimoto, Mai
AU  - Fujimoto M
AD  - Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 
      3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
FAU - Motomura, Haruka
AU  - Motomura H
AD  - Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 
      3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
FAU - Hosomi, Kouichi
AU  - Hosomi K
AD  - Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, 
      3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160101
PL  - Australia
TA  - Int J Med Sci
JT  - International journal of medical sciences
JID - 101213954
RN  - 0 (Anticonvulsants)
RN  - 0 (Sodium Channel Blockers)
SB  - IM
MH  - Anticonvulsants/*adverse effects/therapeutic use
MH  - Data Mining
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Epilepsy/complications/drug therapy
MH  - Humans
MH  - Neoplasms/drug therapy/*epidemiology
MH  - Sodium Channel Blockers/*adverse effects/therapeutic use
MH  - United States
MH  - United States Food and Drug Administration
PMC - PMC4716819
OTO - NOTNLM
OT  - Voltage-gated sodium channels
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2016/01/28 06:00
MHDA- 2016/10/22 06:00
PMCR- 2016/01/01
CRDT- 2016/01/28 06:00
PHST- 2015/09/13 00:00 [received]
PHST- 2015/11/27 00:00 [accepted]
PHST- 2016/01/28 06:00 [entrez]
PHST- 2016/01/28 06:00 [pubmed]
PHST- 2016/10/22 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - ijmsv13p0048 [pii]
AID - 10.7150/ijms.13834 [doi]
PST - epublish
SO  - Int J Med Sci. 2016 Jan 1;13(1):48-59. doi: 10.7150/ijms.13834. eCollection 2016.