Intersecting Pathways to Depression and Evolving Approaches to Pharmacotherapy

Epigenetic regulation of gene expression in the context of changing biological and psychological environments influences risk for major depressive disorder. The purpose of the current mini review is to examine shifts in pharmacotherapeutic targets in relation to two identified risk pathways: the gut-immune-brain axis and hippocampus-pituitary-adrenal axis. Compared to first-line monoamine treatments, neuroactive steroid formulations that enhance inhibitory regulation and reduce neuroinflammation demonstrate a significantly faster and sustained reduction of postpartum depressive symptoms. Serotonergic (5HT) antidepressants with partial agonist actions at the 5HT1A presynaptic receptor demonstrate lower risks for weight gain, sexual impairment, and emotional blunting compared to selective serotonin reuptake inhibitors, but do not appear to improve onset of therapeutic response or response rates.