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- W2327348530 endingPage "655" @default.
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- W2327348530 abstract "Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, 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 TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate 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 MDD. Clinical trials for TRD 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 TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown." @default.
- W2327348530 created "2016-06-24" @default.
- W2327348530 creator A5008127944 @default.
- W2327348530 creator A5014656654 @default.
- W2327348530 creator A5050740394 @default.
- W2327348530 creator A5064016084 @default.
- W2327348530 creator A5068850044 @default.
- W2327348530 date "2015-10-13" @default.
- W2327348530 modified "2023-10-05" @default.
- W2327348530 title "Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review" @default.
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