Major depressive disorder (MDD) is one of the most common mental disorders in everyday clinical practice. Current neuropsychopharmacological approaches to depression are heavily centered on the monoamine hypothesis that depression is caused by defective neurotransmission of serotonin (5-hydroxytriptamine, 5HT), noradrenaline (NA), and dopamine (DA) in the brain.
However, the monoaminergic antidepressants that are currently available have only been shown to achieve remission rates of around 56% after four successive treatment stages, and most of the available antidepressant drugs display problematic side effects and a delayed onset of action. Therefore, more effective and tolerable drugs are urgently needed for the treatment of MDD.
In order to build a comprehensive understanding of the neurobiology of depression and to evaluate alternative pharmacological targets to monoamine neurotransmission, a research team led by Mervin Chávez-Castillo from University of Zulia, Venezuela, reviewed a number of preclinical and clinical studies focused on emerging neuropsychopharmacological approaches to depression management.
In their review article published in Advances in Pharmacological and Pharmaceutical Sciences, the authors found that several neurotransmitters, including glutamate, GABA (γ-Aminobutyric acid) and BDNF (brain-derived neurotrophic factor), have shown to be promising targets in treating MDD during preclinical and clinical trials. In particular, glutamate-based alternatives may be the most feasible in the near future, with promising and active clinical trials currently evaluating the use of both intravenous and oral ketamine, along with several other related molecules.
Furthermore, hormones such as thyroid hormone, corticosteroids and sexual hormones, neurosteroids such as allopregnanolone, and neuropeptides such as oxytocin and galanin have demonstrated the ability to intervene in the neurobiology of depression. It is also argued that reward-related neurotransmitters, such as opioids, endocannabinoids and endovanilloids, are closely linked to the anhedonia and loss of motivation found in depression, and these components have emerged as potential targets in the neuropsychopharmacological treatment of depression.
Although these pharmacological targets have demonstrated evident associations with MDD, the authors argue that research in humans remains scarce, therefore, further studies are required to assuage concerns over the misuse of substances involved in these new treatments. In addition, non-pharmacological interventions such as electroconvulsive therapy and deep brain stimulation have also shown the potential to combat depression and should be further investigated.
This blog post is distributed under the Creative Commons Attribution License (CC-BY). Illustration by David Jury.