The potential antidepressant effect of antidiabetic agents: New insights from a pharmacovigilance study based on data from the reporting system databases FAERS and VigiBase

Background: Growing evidence supports a bidirectional association between diabetes and depression; promising but limited and conflicting data from human studies support the intriguing possibility that antidiabetic agents may be used to relieve effectively depressive symptoms in diabetic patients. We investigated the potential antidepressant effects of antidiabetic drugs in a high-scale population data from the two most important pharmacovigilance databases, i.e., the FDA Adverse Event Reporting System (FAERS) and the VigiBase. Material and methods: From the two primary cohorts of patients treated with antidepressants retrieved from FDA Adverse Event Reporting System and VigiBase we identified cases (depressed patients experiencing therapy failure) and non-cases (depressed patients experiencing any other adverse event). We then calculated the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Empirical Bayes Regression-Adjusted Mean (ERAM) for cases versus non-cases in relation with the concurrent exposure to at least one of the following antidiabetic agent: A10BA Biguanides; A10BB Sulfonylureas; A10BG Thiazolidinediones; A10BH DPP4-inhibitors; A10BJ GLP-1 analogues; A10BK SGLT2 inhibitors (i.e., those agents for which preliminary evidence from literature supports our pharmacological hypothesis). Results: For GLP-1 analogues, all the disproportionality scores showed values <1, i.e., statistically significant, in both analyses [from the FAERS: ROR confidence interval of 0.546 (0.450-0.662); PRR (p-value) of 0.596 (0.000); EBGM (CI) of 0.488 (0.407-0.582); ERAM (CI) of 0.480 (0.398-0.569) and VigiBase: ROR (CI) of 0.717 (0.559-0.921); PRR (p-value) of 0.745 (0.033); EBGM (CI) of 0.586 (0.464-0.733); ERAM of (CI): 0.515 (0.403-0.639)]. Alongside GLP-1 analogues, DPP-4 Inhibitors and Sulfonylureas showed the greatest potential protective effect. With regard to specific antidiabetic agents, liraglutide and gliclazide were associated with a statistically significant decrease in all disproportionality scores, in both analyses. Conclusion: The findings of this study provide encouraging results, albeit preliminary, supporting the need for further clinical research for investigating repurposing of antidiabetic drugs for neuropsychiatric disorders.