Use of Psychedelic Agents in Older Adults with Treatment-Resistant Major Depressive Disorder: What the Evidence Shows.
Lou Vinarcsik, Charles Smoller, George Grossberg
Drugs Aging June 24, 2025 DOI: 10.1007/s40266-025-01221-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Older adults with treatment-resistant major depressive disorder |
| Topics | Depression |
| Keywords | Innovative approach New avenue Agents Treatment Care Novel therapy Untreatable conditions Depressive symptoms Refractory depression Mental health depression Psychological well-being Emotional health Elderly Senior health Aging population |
| Citations | 1 |
| Key findings | Preliminary findings on the safety and tolerability of psychedelic-assisted psychotherapy for treatment-resistant MDD in older adults are promising, but insufficient data leaves concerns unresolved. |
Abstract
The use of drugs with psychedelic and dissociative effects for the treatment of psychiatric illnesses has become increasingly popular in recent years. However, few trials have been conducted to determine the efficacy of these agents in the specific setting of treatment-resistant major depressive disorder (MDD) in older adults. In this paper, we review notable aspects of treatment-resistant MDD in older adults, review classical and nonclassical psychedelic agents and dissociative agents presently being trialed mostly in younger populations for the treatment of depression, and review what is known about trialing these agents in older adults with treatment-resistant MDD. Given the limitations to extant standard treatment and the potential risks associated with first-line pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) in this population, psychedelic-assisted psychotherapy may offer an important alternative for managing treatment-resistant MDD in older adults. This subset of patients is understudied and stands to benefit significantly from improved treatment regimens. The limited research available that details psychedelic-assisted treatment in this specific group is promising. Here we focus on reviewing those agents with the most controlled data available, beginning with the dissociative anesthetic ketamine/esketamine, and the hallucinogenic agent psilocybin, and concluding with a brief review of related substances including lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, ibogaine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline. Treatment-resistant MDD is highly prevalent among older adults, and while preliminary findings seem promising regarding the safety and tolerability of psychedelics, concerns remain owing to insufficient data, and therefore further research is crucial to establish the safety, efficacy, and applications of psychedelic therapy in this population.
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
Cites 53
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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
- 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
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
and 48 more in the library