Long-term use of valproic acid and the prevalence of cancers in bipolar disorder patients in a Taiwanese population: An association analysis using the National Health Insurance Research Database (NHIRD)

Abstract

Background: Epigenetic events play a major role in the carcinogenesis of many cancers. A retrospective cohort study had been performed to evaluate the effects of exposure to the anticonvulsant agent valproic acid (VPA), a histone deacetylase inhibitor, on the risk of developing cancers. Methods: The study was based on the 1998 through 2009 National Health Insurance Research Database (NHIRD), provided by the Taiwan National Health Research Institute. Patients with a diagnosis of bipolar disorder (ICD-9-CM codes 296.0, 296.1, 296.4–8) from 1998 to 2009 were identified. VPA and lithium were the primary index drugs. Patients treated with anticonvulsants who did not use VPA or lithium were selected as the control group. Competing risk regression analysis were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) reflecting the association between use of VPA and cancer incidence. Results: The cancer incidence of bipolar disorder patients treated with VPA was no significant difference than treated with lithium and other anticonvulsants. In subgroup analysis, VPA associated to higher risk of genitourinary cancer in the duration < 1 year group (HR: 3.49; 95%CI: 1.04, 11.67). No significant differences in other cancers incidence in any duration of VPA treatment. Limitations: The cancer prevalence in selected bipolar disorder patients was still low. The sample size was not enough for some types of cancer. Conclusions: A role of VPA in cancer prevention was not found in this study. An increased subgroup risk of genitourinary cancer was observed.