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.
Niharika Singh, Puja Panwar Hazari, Parul Mittal, Shiv Kumar Yadav, Nitin Kumar, Gauri Mishra, Saurabh Dahiya, Anil Kumar Mishra
European Journal of Pharmacology August 15, 2025 DOI: 10.1016/j.ejphar.2025.177737 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Serotonin |
| Keywords | Serotonin-norepinephrine reuptake inhibitors Antidepressants ssris Snris Antidepressive agents Mood stabilizers Psychedelics hallucinogens Psychedelic drugs Entheogens Neuroscience brain chemistry |
| Citations | 16 |
| Key findings | SSRIs, SNRIs, and psychedelics are key antidepressants; psychedelics show promise through polypharmacology and fMRI reveals their effects on brain dynamics. |
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.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cites 54
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 49 more in the library