Editorial: Perspectives on new fast-acting antidepressants

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Perspectives on new fast-acting antidepressantsClassic antidepressants typically require weeks to months to produce clinically significant effects.Considering that only one-third of patients achieve remission from depression with their first prescribed drug (1), a large proportion of patients will be submitted to several lengthy trials of antidepressants, and a big part of treatment time will be spent waiting and hoping for medications to end up working.Considering also that depressed individuals who commit suicide frequently seek help from mental health professionals weeks prior to completion of suicide, there is an emerging need for treatments with a faster onset of antidepressant action.In recent years, there has been a notable emergence of compounds identified as "rapidacting antidepressants (RAADs)", sparking significant interest in understanding the mechanisms behind these drugs' ability to elicit such quick responses.NMDA (Nmethyl-D-aspartate) antagonism, a property shared by ketamine, esketamine, and dextromethorphan, is thought to be one of the mechanisms contributing to rapid antidepressant effects.However, it's not likely to be the ultimate pathway; instead, it acts as a mediator for the rapid release of BDNF (Brain-Derived Neurotrophic Factor).Other substances with demonstrated RAAD proprieties are scopolamine, brexanolone, zuranolone and psilocybin.Scientific papers examining the perspectives of RAADs in psychiatry have been gathered in this Research Topic.Aiming to broaden the clinical uses of NMDA-antagonists in psychiatry, Gan et al. evaluated a new potential esketamine property: its effect on reducing postoperative depressive symptoms on patients undergoing lung cancer surgery.Examining 156 patients, in a randomized double-blind, placebo-controlled design, the authors evaluated whether intravenous intraoperative and postoperative (up to 48 hours) esketamine could reduce the development of depressive symptoms.The incidence of depressive symptoms measured by the Beck Depression Inventory-II 1 month postoperativelywas lower in the esketamine group (1.3%) as compared to the placebo (saline) group (11.8%).Two risk factors for postoperative depressive symptoms identified were preoperative anxiety and hypertension.Yavorsky et al. stated recommendations on how to select and adapt currently used clinical rating scales for the use on clinical trials for RAADs.This is a subject of great importance, since the instruments most frequently used today were developed many decades ago, and were designed to best capture the effects of monoaminergic Frontiers in Psychiatry frontiersin.

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