Abstract
Depression is currently recognized as a crucial problem in everyday clinical practice, in light of ever-increasing rates of prevalence, as well as disability, morbidity, and mortality related to this disorder. Currently available antidepressant drugs are notoriously problematic, with suboptimal remission rates and troubling side-effect profiles. Their mechanisms of action focus on the monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. Nevertheless, views on the pathophysiology of depression have evolved notably, and the comprehension of depression as a complex neuroendocrine disorder with important systemic implications has sparked interest in a myriad of novel neuropsychopharmacological approaches. Innovative pharmacological targets beyond monoamines include glutamatergic and GABAergic neurotransmission, brain-derived neurotrophic factor, various endocrine axes, as well as several neurosteroids, neuropeptides, opioids, endocannabinoids and endovanilloids. This review summarizes current knowledge on these pharmacological targets and their potential utility in the clinical management of depression.
Highlights
Depression is one of the most frequent mental disorders in everyday clinical practice and is currently regarded as the leading cause of disability worldwide [1]
E development of newer, more effective, and tolerable agents is a pressing matter in neuropsychopharmacology, yet relatively few new drugs have been approved for major depressive disorder (MDD) in recent decades [6]
Both the limited effectivity of existing antidepressant drugs (AD) and the scarcity of novel options may stem from a once revolutionary, yet—in retrospect—excessive and misguided focus on the monoamine hypothesis for the pathophysiology of depression, which centers on defective neurotransmission of serotonin (5-hydroxytriptamine, 5HT), noradrenaline (NA), and dopamine (DA) in the brain [7]
Summary
Depression is one of the most frequent mental disorders in everyday clinical practice and is currently regarded as the leading cause of disability worldwide [1]. Clinical research on repastinel is only in its early stages, repastinel appears to induce rapid and sustained antidepressant e ects and be well-tolerated with no psychotomimetic e ects [43] In contrast with these rather selective glutamatergic agents, scopolamine, a nonselective muscarinic receptor antagonist, displays Glu-modulating activity, which may correlate with antidepressant e ects [44]. It is a Glu receptor modulator [58] with apparent efficacy as both monotherapy [52] and adjunctive therapy in patients with treatmentresistant major depressive disorder (MDD) [59] Research has found this antidepressant effect to be especially notable at 4 weeks in treatment-resistant populations, placebo-controlled studies tend to deny any significant differences [60].
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