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

Abstract

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 suchas combining PPAR (α/γ) agonist with noradrenaline dopamine reuptake inhibitor, gap junction channelmodulator/hemichannel inhibitor with N-methyl-D-aspartate receptor antagonist like ketamine, ω-3 fattyacids derivatives like resolvin with tricyclic antidepressant like amineptine, RAAS-modifying drugswith serotonin reuptake inhibitors such as fluoxetine, ceramide synthase inhibitor/acid sphingomyelinaseinhibitor with doxepin, and HPA axis-modifying drugs with bupropion. Further assessment of thesecombination approaches may help in availing better therapeutic options in the treatment of depression.