Diverse faces of antidepressant drugs

Abstract

The high status of antidepressant drugs results from the fact that depression is one of the most common pathological conditions in medicine. Seventy years ago, during the pharmacological revolution in psychiatry, antidepressant drugs appeared as acting therapeutically on depression. Tricyclic antidepressants and monoamine oxidase inhibitors made up the first generation of these drugs. Their mechanism of action suggested enhancement of noradrenergic, dopaminergic, and serotonergic neurotransmission in the central nervous system. Nowadays, a similar interpretation remains relevant to the majority of antidepressant drugs.
Neurotransmitter concepts, mainly the serotonergic one, contributed to the discovery and introduction of new antidepressants. Selective serotonin reuptake inhibitors (SSRIs) have been the most frequently used antidepressants. The introduction of the SSRI fluoxetine in the USA, named Prozac, at the turn of 1980/1990 made a cultural event. In the 21st century, serotonin was on the rise
as a hormone of “happiness” and appeared in literature. However, in recent decades, antidepressant drugs have raised numerous controversies, especially concerning their limited efficacy and adverse effects. The introduction of ketamine as an antidepressant drug in the first decade of the 21st century featured a role of glutamatergic neurotransmission in depression’s pathogenesis. Whereas in recent years, antidepressant activity of psychedelic substances, mainly psilocybin, was ascertained.