Role of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and psychedelics in the treatment of major depressive disorder: A perspective on mechanistic insight and current status.

Depression impairs cognition, learning, and memory by disrupting brain chemistry. The monoamine hypothesis links depression to low serotonin, dopamine, and norepinephrine. Antidepressants such as SSRIs and SNRIs, which block serotonin and norepinephrine transporters, are primary treatments for major depressive disorder. Recently, psychedelics have gained importance as antidepressants. This review covers SSRIs, SNRIs, and psychedelics, their target receptors, and recent treatment advances. It also discusses the polypharmacology of psychedelics and fMRI studies that illuminate brain dynamics under psychedelics.

Study at a glance

Abstract

Globally, depression affects millions of people of all ages, making it one of the significant contributors to deteriorating quality of life by causing neurological impairments that eventually weaken cognition, learning, and memory. According to the monoamine hypothesis, depression is associated with decreased serotonin, dopamine, and norepinephrine levels in the central nervous system. Drugs that inhibit serotonin (5-HT) and norepinephrine (NE) transporters have gained recognition in drug discoveries concerning antidepressants. Both the serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) have been significantly involved as the primary medication for major depressive disorder. Recently, the use of psychedelics has gained much importance in antidepressant medications. In this review, we explore a comprehensive overview of different types of antidepressants like SSRIs, SNRIs, and psychedelics, along with their respective target receptors, and their role in recent advancements in treating depression. Furthermore, we discuss the polypharmacology of psychedelics and functional magnetic resonance imaging (fMRI) studies to enhance our understanding of the brain dynamics due to psychedelics.