Diabetes and mood disorders: shared mechanisms and therapeutic opportunities.

The objective of this manuscript is to provide a comprehensive and critical overview of the current evidence on the association between Diabetes mellitus (DM) and mood disorders [i.e., Major depressive disorder (MDD) and bipolar disorder (BD)], and therapeutic opportunities. We searched in MEDLINE (via Ovid) for placebo-controlled clinical trials published in the last 20 years that assessed drug repurposing approaches for the treatment of DM or mood disorders. We found seven studies that aimed to verify the effects of antidepressants in patients diagnosed with DM, and eight studies that tested the effect of antidiabetic drugs in patients diagnosed with MDD or BD. Most studies published in the last two decades did not report a positive effect of antidepressants on glycemic control in patients with DM. On the other hand, antidiabetic drugs seem to have a positive effect on the treatment of MDD and BD. While effect of antidepressants on glycemic control in patients with DM is still controversial, the use of antidiabetic drugs may be a promising strategy for patients with MDD or BD. Prospective studies are still needed.Key pointsMood disorders in patients with DM affect glycemic control, potentially increasing mortality risk.The effect of antidepressants on glycemic control in patients with DM is still controversial. The coexistence of complicated DM and a mood disorders would require a careful, individualised, and comprehensive evaluation.Insulin resistance may increase the risk of depressive symptoms and is associated with worse outcomes in BD.The use antidiabetic drugs may be a promising strategy for patients with MDD or BD. However, prospective trials are needed to prove a potential antidepressant activity of antidiabetic drugs.