The latest steps in antidepressant treatment: present and future

Abstract

Depression is among the most common psychiatric diseases in today’s society, and its incidence is steadily increasing. Many theories have attempted to explain depression’s origin and etiology, the most relevant being the monoaminergic, the neurotrophic, and the neuroinflammatory hypothesis of depression, but various aspects of its neurobiology are still unknown. This review discusses their origin, evidence and features, along with a few other theories’. In the past, antidepressant drug discovery happened by chance, and the study of effective substances at improving symptoms contributed greatly to the knowledge of the neurobiology of depression.

Classical antidepressants constitute the base of the pharmacological treatment of depression: monoaminoxidase inhibitors, tricyclic antidepressants and monoamine reuptake inhibitors. Newer drugs, like trazodone and mirtazapine, possess a more complex pharmacodynamic profile. With the aim to avoid their usual adverse effects, and to improve their effectiveness, alternative mechanisms have been explored. This research has resulted in the discovery of substances such as agomelatine, tianeptine and vortioxetine, but their use and efficacy are not very widespread. Nonetheless, ketamine has recently revolutionised the research of antidepressants, since it has proven to be a fast-acting, potent antidepressant, even in resistant cases, in addition to being safe and well-tolerated. Lastly, psychedelic substances have been known to improve symptoms of a variety of psychiatric diseases, including depression. Specifically, psilocybin has shown great prospects as an antidepressant in a number of studies. Despite its undeniable beneficial effects on depressed patients, its antidepressant mechanisms are not entirely clear, and research in the field is currently trending.