A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis.
Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed.



We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male.



Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.
Department of Drug Evaluation & Informatics, Graduate school of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.|Department of Biostatistics, Shionogi Pharmaceutical Company, Osaka, Japan.
Masakazu
M
Fujiwara
Department of Drug Evaluation & Informatics, Graduate school of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Yohei
Y
Kawasaki
Department of Drug Evaluation & Informatics, Graduate school of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Hiroshi
H
Yamada
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000410:Alanine Transaminase / Q000097:blood; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016208:Databases, Factual; D003863:Depression / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007564:Japan; D008297:Male; D040541:Marketing / Q000941:ethics; D009459:Neuroleptic Malignant Syndrome / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D060735:Pharmacovigilance; D012206:Rhabdomyolysis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D012737:Sex Factors; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data
D000928:Antidepressive Agents; D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase