New and emerging treatments for major depressive disorder.
Cecilia Njenga, Parashar Pravin Ramanuj, Frederico José Coelho de Magalhães, Harold Alan Pincus
BMJ July 8, 2024 DOI: 10.1136/bmj-2022-073823 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Citations | 44 |
| Key findings | Psychedelics show promise as rapid-acting treatments for MDD, but current research limitations prevent strong recommendations. |
Abstract
Major depressive disorder (MDD) affects a substantial portion of the population; however, much is still unknown about the pathophysiology of this disorder. Treatment resistance highlights the heterogeneous nature of MDD and the need for treatments to target more than monoamine neurotransmission. This review summarizes research into the new and emerging targets of MDD. These include drugs such as psychedelics, antibiotics, opioid modulators, neuropeptides, and onabotulinumtoxin. Neuromodulatory treatments such as light based therapies and neuromodulation involving either magnetic or electrical stimulation are also discussed. Almost all interventions, pharmacological and neuromodulation, were trialed as adjunctive treatments to an antidepressant. Most research has been conducted on psychedelics, with trials suggesting rapid antidepressant and anti-suicidal effects. Trial findings, tolerability, study design limitations and quality of research have been considered throughout this review. There remains challenges in forming recommendations with the current research at present. With there being considerable interest into the research of new and emerging treatments-in particular, psychedelics-there may be scope in the future to form more robust recommendations.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 8
- Randomized Controlled Trials of Psilocybin‐Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta‐Analysis Acta Psychiatrica Scandinavica December 3, 2024
- Non-response to short-term ketamine use for treatment-resistant depression. Pharmacological Reports April 30, 2025
- Therapeutic effects of psilocybin in major depressive disorder: a systematic review and meta-analysis exploring dose effects. European Archives of Psychiatry and Clinical Neuroscience June 1, 2026
- Discovery of Rapid-Acting, Orally Available Antidepressants by Activating TrkB Signaling. Journal of Medicinal Chemistry July 29, 2025
- Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts Biochemistry and Cell Biology 2025
and 3 more in the library
Cites 31
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
and 26 more in the library