Abstract
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.