Vekhova Ksenia A, Namiot Eugenia D, Jonsson Jörgen, Schiöth Helgi B
Functional Pharmacology and Neuroscience, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.
Ketamine has a long and very eventful pharmacological history. Its enantiomer, esketamine ((S)-ketamine), was approved by the US Food and Drug Administration (FDA) and EMA for patients with treatment-resistant depression (TRD) in 2019. The number of approved indications for ketamine and esketamine continues to increase, as well as the number of clinical trials. This analysis provides a quantitative overview of the use of ketamine and its enantiomers in clinical trials during 2014-2024. A total of 363 trials were manually assessed from clinicaltrial.gov with the search term "Ketamine." The highest number of trials were found for the FDA-approved indications: anesthesia (22%) and pain management (28%) for ketamine and TRD for esketamine (~29%). Clinical trials on TRD for both ketamine and esketamine also comprised a large proportion of these trials, and interestingly, have reached phase III and phase IV status. Combinatorial treatment of psychiatric disorders and non-psychiatric conditions with pharmacological and non-pharmacological combinations (electroconvulsive therapy, psychotherapeutic techniques, virtual reality, and transcranial magnetic stimulation) is prevalent. Sub-anesthetic doses of ketamine may represent novel therapeutic avenues in neuropsychiatric conditions, that is, major depression, schizophrenia, and bipolar disorder, where glutamate excitotoxicity and oxidative stress are likely to be involved. The study suggests that the number of ketamine studies will continue to grow and possible ketamine variants can be approved for treatment of additional indications.
氯胺酮有着悠久且极为丰富的药理史。其对映体艾氯胺酮（(S)-氯胺酮）于2019年获美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准用于治疗抵抗性抑郁症（TRD）患者。氯胺酮和艾氯胺酮获批的适应症数量以及临床试验数量都在持续增加。本分析提供了2014年至2024年期间氯胺酮及其对映体在临床试验中使用情况的定量概述。通过在clinicaltrial.gov上使用搜索词“氯胺酮”手动评估了总共363项试验。发现FDA批准适应症的试验数量最多：氯胺酮用于麻醉（约22%）和疼痛管理（约28%），艾氯胺酮用于TRD（约29%）。氯胺酮和艾氯胺酮针对TRD的临床试验在这些试验中也占很大比例，有趣的是，已进入III期和IV期。使用药物和非药物组合（电休克疗法、心理治疗技术、虚拟现实和经颅磁刺激）对精神疾病和非精神疾病进行联合治疗很普遍。亚麻醉剂量的氯胺酮可能代表神经精神疾病（即重度抑郁症、精神分裂症和双相情感障碍）中的新型治疗途径，这些疾病可能涉及谷氨酸兴奋性毒性和氧化应激。该研究表明氯胺酮研究数量将继续增长，并且可能有更多氯胺酮变体获批用于其他适应症的治疗。
