Ingrosso Gianmarco, Cleare Anthony J, Juruena Mario F
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Health Sciences, University of Milan, Milan, Italy.
J Psychopharmacol. 2025 Jan;39(1):49-65. doi: 10.1177/02698811241303597. Epub 2024 Dec 17.
Ketamine has demonstrated both rapid and sustained efficacy in treating depression, especially in treatment-resistant cases. However, concerns regarding the addictive potential of ketamine during long-term depression treatment persist among clinicians.
This review aimed to summarise the evidence on addiction phenomena associated with ketamine treatment of depression.
A comprehensive search was conducted in MEDLINE, Embase, PsycInfo and Global Health databases, with additional relevant studies identified through reference lists. Sixteen studies were included, comprising six randomised controlled trials, three single-arm open-label studies, one retrospective study, three case series and three case reports, for a total of 2174 patients.
The studies employed various routes of administration, including intravenous, intramuscular, intranasal, oral and sublingual. Ketamine was administered in the racemic form, except for the studies that utilised intranasal esketamine. Among the included population, four patients were reported to exhibit clear signs of tolerance to the antidepressant effect of ketamine or dependence on the drug, while the majority did not. Cases of addiction phenomena reported in studies that did not meet the inclusion criteria are also discussed.
Despite the heterogeneity in study designs and outcome assessment methods, the review underscores the relative safety of ketamine treatment for adult patients with depression, emphasising the importance of medically supervised administration, vigilant monitoring and judicious dosing. Future long-term studies employing quantitative scales to assess dependence phenomena could contribute to strengthening the evidence for the safe and effective use of ketamine in the treatment of depression.
氯胺酮已被证明在治疗抑郁症方面具有快速且持久的疗效，尤其是在难治性病例中。然而，临床医生对氯胺酮在长期抑郁症治疗期间的成瘾潜力仍存在担忧。
本综述旨在总结与氯胺酮治疗抑郁症相关的成瘾现象的证据。
在MEDLINE、Embase、PsycInfo和全球健康数据库中进行了全面检索，并通过参考文献列表确定了其他相关研究。纳入了16项研究，包括6项随机对照试验、3项单臂开放标签研究、1项回顾性研究、3项病例系列和3项病例报告，共计2174例患者。
这些研究采用了多种给药途径，包括静脉注射、肌肉注射、鼻内给药、口服和舌下给药。除了使用鼻内艾氯胺酮的研究外，氯胺酮均以外消旋形式给药。在所纳入的人群中，有4例患者被报告对氯胺酮的抗抑郁作用表现出明显的耐受性迹象或对该药物产生依赖，而大多数患者没有。还讨论了未符合纳入标准的研究中报告的成瘾现象病例。
尽管研究设计和结果评估方法存在异质性，但该综述强调了氯胺酮治疗成年抑郁症患者的相对安全性，强调了医学监督给药、密切监测和合理给药的重要性。未来采用定量量表评估依赖现象的长期研究可能有助于加强氯胺酮在抑郁症治疗中安全有效使用的证据。
