The Association between Lithium used and Cancer Occurrence in Bipolar Disorder

• Main Authors: Ru-Yu Huang, 黃如玉
• Other Authors: Yi-Hsin Yang
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/22da9b

碩士 === 高雄醫學大學 === 藥學系臨床藥學碩士班 === 103 === Background: The use of glycogen synthase kinase-3 (GSK-3) is associated with several human diseases including cancer in in vitro studies or animal models. Whether the impact of GSK-3 is positive or negative on tumor development is speculated on the type of tumor tissue. Lithium is one of the GSK-3 inhibitors. Clinical studies on the association between the GSK-3 inhibitor and cancer occurrence are still limited. The aim of this study was to determine the lithium effect on cancer occurrence, and further to investigate whether there is a dose-response association on the usage of lithium in bipolar disorder patients. Methods: We conducted a population-based retrospective cohort study using the Taiwan Longitudinal Health Insurance Database 2005. Newly-diagnosed bipolar disorder patients during 1998-2009 were first extracted. We further included patients with at least one medication for bipolar disorder in the study cohort. The study population was then divided into 3 groups: lithium only, anticonvulsants only, and ever exposure to lithium and anticonvulsants. The cumulative define daily dose (DDD) and prescription days were computed for the 3 groups. The inverse probability of treatment weighted (IPTW) method based on the propensity score was used to balance confounding factors between the groups. The Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the occurrence of cancer. Analysis covariates also included time-dependent covariates and co-medications. Results: There were 115 cancers (86, 6 and 23 in the anticonvulsants, lithium, and lithium?yanticonvulsant group, respectively) identified by the registry dataset for catastrophic illness patients from 4729 bipolar disorder patients (3250, 370 and 1109 in the anticonvulsants, lithium and lithium?yanticonvulsant group, respectively). The results of univariate analysis showed a significant decreased in HR (HR=0.426, 95%CI=0.186-0.975 for lithium only group; HR=0.511, 95%CI=0.322-0.812 for lithium ?yanticonvulsants group). After weighted by IPTW and adjusted for additional cofounders, the Cox regression analysis showed that lithium ?banticonvulsants group (HR=0.742, 95%CI=0.557-0.989), high cumulative dose of lithium (HR=0.594, 95%CI=0.394-0.898) were significantly associated with a decreased cancer risk. The result of cumulative prescription days did not show a trend for decreased cancer risk. Conclusion: Lithium as a GSK-3 inhibitor has been investigated to have an effect on the cancer development on both in vivo and in vitro studies. We investigate the relationship between lithium and cancer risk base on large-scale population database. Our result implies that the lithium use was negatively associated with incidence of overall cancer in bipolar disorder. There is a dose-response relationship in the lithium usage and risk reduction. Further studies could focus on the various tissue type of cancer.