Debating the "bidirectional link" between diabetes and depression through the Ca2+/cAMP signalling: Off-label effects of Ca2+ channel blockers.

Many reports have been demonstrating off-label effects for calcium (Ca2+) channel blockers (CCBs), for example: patients medicated with CCBs have had an improvement of their diabetes status (control of glycemia), along with an improvement of both depression symptoms and cognitive function. Indeed, diabetes and depression are medical problems both with clearly restricted pharmacotherapies, along with a high prevalence around the world, then costing millions and millions for the medical health systems. Furthermore, the incidence of depression is till three times higher in patients with diabetes. In addition, depression may augment the risk of developing type 2 diabetes till 60%. Then, there is a clear "bidirectional link" between depression and diabetes, reflecting substantial interactions in their etiology. But which are the possible cellular mechanisms for this "bidirectional link" between depression and diabetes, and for the off-label effects of CCBs? Considering our previously cited international articles, which demonstrated the role of the Ca2+/cAMP signalling in regulating both the neurotransmitter release and the neuronal death, in this review I have debated the possible involvement of the Ca2+/cAMP signalling in the off-label effects of CCBs, including the role of the Ca2+/cAMP signalling in the "bidirectional link" between diabetes and depression.