Quintero Jose Manuel, Bustos Rosa Helena, Lechtig-Wassermann Sharon, Beltran Stephania, Zarate Carlos A
Department of Clinical Pharmacology, Evidence-Based Therapeutics Group, Faculty of Medicine, https://ror.org/02sqgkj21Universidad de La Sabana and Clínica Universidad de La Sabana, Chía, Colombia.
Doctoral Programme of Biosciences, Universidad de La Sabana, Chía, Colombia.
CNS Spectr. 2025 Jun 30;30(1):e51. doi: 10.1017/S1092852925100333.
Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry, ketamine remains a valuable anesthetic and analgesic agent with applications in acute and chronic pain management. Its anti-inflammatory, neuroprotective, and potential antitumor properties further underscore its versatility in clinical medicine. Despite its therapeutic promise, ketamine poses challenges due to its dissociative and hallucinogenic effects, contributing to widespread recreational use. Chronic misuse is associated with adverse health outcomes, including bladder dysfunction and hepatobiliary complications. As a result, ketamine has been subject to increasing regulatory scrutiny, balancing its medical utility with concerns about abuse potential. The rediscovery of ketamine's antidepressant effects in the early 2000s has revolutionized psychiatric treatment, particularly in TRD and suicidality. Recent studies have also explored its efficacy in bipolar depression, posttraumatic stress disorder, obsessive-compulsive disorder, and substance use disorders, expanding its therapeutic applications. Additionally, ongoing research aims to elucidate its long-term effects and optimize dosing regimens to maximize clinical benefits while minimizing risks. This review highlights ketamine's multifaceted pharmacological properties, its evolution from an anesthetic to a novel psychiatric treatment, and its broader medical applications. As research advances, a comprehensive understanding of ketamine's mechanisms and clinical implications will be crucial for optimizing its therapeutic potential while mitigating its risks.
氯胺酮于1962年首次合成，因其在难治性抑郁症（TRD）中具有快速且持久的抗抑郁作用而受到越来越多的关注。与传统抗抑郁药不同，氯胺酮作用于多个神经递质系统，包括N-甲基-D-天冬氨酸（NMDA）受体拮抗和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体增强，为情绪调节提供了一种新机制。除了精神病学领域，氯胺酮仍然是一种有价值的麻醉和镇痛药，可用于急性和慢性疼痛管理。其抗炎、神经保护和潜在的抗肿瘤特性进一步凸显了其在临床医学中的多功能性。尽管氯胺酮具有治疗前景，但由于其解离和致幻作用，导致其被广泛用于娱乐，带来了挑战。长期滥用与不良健康后果相关，包括膀胱功能障碍和肝胆并发症。因此，氯胺酮受到了越来越多的监管审查，需要在其医疗效用与滥用可能性之间进行权衡。21世纪初氯胺酮抗抑郁作用的重新发现彻底改变了精神病学治疗，尤其是在难治性抑郁症和自杀倾向方面。最近的研究还探讨了其在双相抑郁症、创伤后应激障碍、强迫症和物质使用障碍中的疗效，扩大了其治疗应用范围。此外，正在进行的研究旨在阐明其长期影响并优化给药方案，以在将风险降至最低的同时最大化临床益处。本综述强调了氯胺酮多方面的药理特性、其从麻醉剂到新型精神病学治疗药物的演变以及其更广泛的医学应用。随着研究的进展，全面了解氯胺酮的作用机制和临床意义对于优化其治疗潜力同时降低风险至关重要。
