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

Abstract

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.

The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression

“…There is evidence that metformin can control antipsychotic induced MetS in schizophrenic patients ( 28 ). Of importance, its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated ( 29 ). According to recent preclinical and clinical findings, metformin can penetrate through the Blood–Brain Barrier (BBB) into the central nervous system (CNS) where it promotes neuroprotective, neurotrophic, neurogenetic and anti-inflammatory effects ( 30 ).…”

Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database

“…In combination with neuropsychiatric drugs, GLP-1RAs did not increase the risk of developing SSIBs. Moreover, GLP-1RAs have cognition-promoting effects and activate the GLP-1R/cAMP/PKA pathway, thus providing a new intervention for the treatment of depression and reduction of SSIBs [ 36 , 47 , 48 ]. These studies provide a comprehensive and accurate biological perspective for a deeper understanding of the association between GLP-1RAs and SSIBs.…”

Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems

“…Very recently, DAs have been provisionally explored to identify candidates for drug reposition, which have been subsequently tested in vitro as part of a translational approach (Chrétien et al, 2021). It is important to remark that such novel pioneering approaches should not only take into account all the potential biases that have been described so far, but also the available pharmacological evidence (Battini et al, 2023b). Any potential use of spontaneous reporting databases for drug repurposing should be possibly validated and confirmed in vivo, ex vivo and in clinical trials before becoming a consolidated approach.…”