Psychedelics for treatment resistant depression: are they game changers?
Michail Kalfas, Rosie H Taylor, Dimosthenis Tsapekos, Allan H. Young
Expert Opinion on Pharmacotherapy November 10, 2023 DOI: 10.1080/14656566.2023.2281582 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Double-blind Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression |
| Intervention | Psilocybin |
| Duration | At least 3 months |
| Topics | Depression Psilocybin |
| Keywords | Systematic review Treatment resistant depression Psychedelics hallucinogens Entheogens Mood disorder therapy Mental health treatment Psychedelic medicine trials Psychoactive drugs |
| Citations | 28 |
| Key findings | Psilocybin shows a rapid antidepressant effect sustained for at least three months in some responders with treatment-resistant depression. |
Abstract
Psychedelic therapy has created a paradigm shift in the treatment of TRD, as it can maximize therapeutic benefits and minimize potential risks. Psilocybin holds promise as a potential game-changer in the treatment of TRD, with initial evidence suggesting a rapid antidepressant effect sustained for some responders for at least 3 months. Nevertheless, further adequately powered, double-blind, comparator-controlled trials are required to explore and clarify the mechanisms of action and long-term effects of psychedelics in TRD. Psychedelics also hold promise for other psychiatric conditions, such as bipolar depression and post-traumatic stress disorder.
Comparable studies
Other narrative reviews on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression | 2021 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review | 2020 | Review | |
| From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders | 2021 | Review |
Citations in the library
Cited by 27
- Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study. Journal of Affective Disorders January 15, 2025
- 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
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression. European Archives of Psychiatry and Clinical Neuroscience August 29, 2024
- Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT2A receptor agonists. British Journal of Pharmacology May 23, 2025
- Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder Journal of Psychedelic Studies September 4, 2025
and 22 more in the library
Cites 92
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- 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
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 87 more in the library