Novel Pharmacological Approaches to the Treatment of Depression

Abstract

Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

The Effects of Prenatal Dexamethasone Exposure on Brain Metabolic Homeostasis in Adulthood: Implications for Depression

“…Mental disorders refer to a wide range of mental health conditions that are among the most important health problems of the 21st century, and among them, the soaring incidence of depression is a serious challenge to contemporary medicine [ 1 ]. Despite many years of research and a variety of pharmacological approaches [ 2 ], this disease still produces a long-term negative impact on the quality of life and a significant reduction in life expectancy. Depression is a complex disorder characterized by alterations in several biological systems, including genetic, neuroendocrine, biological, psychosocial, and environmental interactions.…”

Gypenoside XVII, an Active Ingredient from Gynostemma Pentaphyllum, Inhibits C3aR-Associated Synaptic Pruning in Stressed Mice

“…Meanwhile, Gypenoside XVII did not affect the crossing and rearing numbers in the openfield tests. On the other hand, the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the common neurobiological abnormalities in the serum of patients with depression [23]; the biochemical analysis provided evidence that Gypenoside XVII decreased the levels of corticosterone, the core hormone of the HPA axis. These observations above, for the first time, clearly demonstrate the antidepressant-like effects of Gypenoside XVII.…”

Efficacy, Tolerability, and Safety of Toludesvenlafaxine for the Treatment of Major Depressive Disorder—A Narrative Review

“…The importance of TRI investigation is derived from theoretical and pragmatic reasons. As previously mentioned, the monoamine hypothesis is under extensive scrutiny for its clinical limitations, and new theoretical frameworks for MDD have been formulated, based on other neurotransmitters’ dysfunction, gut microbiome alterations, inflammatory factors, immune or hypothalamic–pituitary–adrenal axis dysregulation, and neurogenesis or cholesterol biosynthesis pathway impairments [ 29 , 67 , 68 , 69 , 70 , 71 ]. Still, the monoaminergic system is considered a central element in the pathogenesis of MDD, although multiple interactions with other CNS pathways are also important for the understanding of this disorder [ 72 , 73 ].…”