Novel Therapeutic Targets for Major Depressive Disorder

Major depressive disorder (MDD) is one of the most commonly diagnosed disorders and represents large societal and individual costs. Despite the clinical significance of MDD, our current treatments often remain inadequate to elicit sufficient response, or ideally, remission. Roughly one-third of depressed patients do not respond at all to first-line antidepressants. In this chapter, we outline some of the novel pathways that have recently been implicated in the pathogenesis of MDD in the hopes of developing novel, more effective treatments. In addition, we overview clinical evidence for numerous pharmaceutical agents within each pathway. We investigate inflammatory pathways, oxidative and nitrosative stress, the hypothalamic-pituitary-adrenal axis, glucose metabolism, bioenergetics, the one-carbon cycle, neurotrophins, the glumatergic system, opioids, and the cholinergic system. In describing each pathway as a novel treatment target, we attempt to emphasize the need for increasingly personalized treatments for the heterogeneous phenotypic presentations of MDD.