Vinarcsik Lou, Smoller Charles, Grossberg George
Division of Geriatric Psychiatry, Department of Psychiatry & Behavioral Neuroscience, Saint Louis University School of Medicine, St. Louis, MO, USA.
Drugs Aging. 2025 Jun 24. doi: 10.1007/s40266-025-01221-5.
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.
近年来，使用具有致幻和解离作用的药物治疗精神疾病越来越普遍。然而，很少有试验来确定这些药物在老年难治性重度抑郁症（MDD）特定治疗环境中的疗效。在本文中，我们回顾了老年难治性MDD的显著方面，回顾了目前主要在年轻人群中试验用于治疗抑郁症的经典和非经典致幻剂及解离剂，并回顾了在患有难治性MDD的老年人中试验这些药物的已知情况。鉴于现有标准治疗的局限性以及该人群中一线药理药物（如选择性5-羟色胺再摄取抑制剂（SSRI））相关的潜在风险，致幻剂辅助心理治疗可能为管理老年难治性MDD提供重要的替代方案。这一患者亚群研究不足，有望从改进的治疗方案中显著获益。现有关于该特定群体致幻剂辅助治疗的有限研究很有前景。在这里，我们重点回顾那些有最可控数据的药物，首先是解离麻醉剂氯胺酮/艾氯胺酮，以及致幻剂裸盖菇素，最后简要回顾相关物质，包括麦角酸二乙酰胺（LSD）、N,N-二甲基色胺（DMT）、死藤水、伊博格碱、3,4-亚甲基二氧甲基苯丙胺（MDMA）和三甲氧苯乙胺。难治性MDD在老年人中非常普遍，虽然关于致幻剂的安全性和耐受性的初步研究结果似乎很有前景，但由于数据不足，仍存在担忧，因此进一步研究对于确定致幻剂疗法在该人群中的安全性、疗效和应用至关重要。
