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.
European journal of pharmacology – August 15, 2025
Source: PubMed
Summary
Modern antidepressants and psychedelics work by targeting brain chemistry in distinct ways. While traditional medications like selective serotonin reuptake inhibitors increase available serotonin gradually, psychedelics create rapid changes in brain connectivity. Brain imaging shows both approaches effectively treat depression, though through different mechanisms. This dual perspective offers promising options for personalized treatment.
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.