Possible Targets Related to Connexins and Ceramides in the Treatment of Depression Using a Combination Approach

The novel targets considered in the recent research related to the treatment of depression include connexins, peroxisome proliferator activated receptor (PPAR), ω-3 fatty acids, ceramides, and renin–angiotensin– aldosterone system (RAAS). The major associated brain parts considered include hypothalamus, pituitary, and adrenal gland (HPA) axis in psychiatric disorders. The present review has proposed hypotheses such as combining PPAR (α/γ) agonist with noradrenaline dopamine reuptake inhibitor, gap junction channel modulator/hemichannel inhibitor with N-methyl-D-aspartate receptor antagonist like ketamine, ω-3 fatty acids derivatives like resolvin with tricyclic antidepressant like amineptine, RAAS-modifying drugs with serotonin reuptake inhibitors such as fluoxetine, ceramide synthase inhibitor/acid sphingomyelinase inhibitor with doxepin, and HPA axis-modifying drugs with bupropion. Further assessment of these combination approaches may help in availing better therapeutic options in the treatment of depression.