Beyond XXXX -Novel Targets for Treatment-Resistant Depression: A Comprehensive Review.

@entity1 @entity308 @entity3264 @entity13217 @entity2339 @entity1154
@entity308 ( @entity308 ) is a leading cause of disability worldwide. Current first line therapies target modulation of the @entity1154 system. A large variety of agents are currently available that effectively alter @entity1154 levels; however, approximately one third of @entity308 @entity1 remain treatment refractory after adequate trials of multiple @entity1154 based therapies. Therefore, @entity1 with @entity13217 ( @entity13217 ) may require modulation of pathways outside of the classic @entity1154 system. The purpose of this review was thus to discuss novel targets for @entity13217 , to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of @entity13217 have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the @entity2339 , the metabolic and bioenergetics system, neurotrophic pathways, the @entity3264 system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of @entity308 . Clinical trials for @entity13217 have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for @entity13217 . As well, several promising novel agents have been clinically tested in @entity308 populations, but have yet to be assessed specifically for @entity13217 . Thus, their applicability to @entity13217 remains unknown.
