Na Kyoung-Sae, Kim Yong-Ku
Department of Psychiatry, Gachon University Gil Medical Center, Incheon, Republic of Korea.
Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110060. doi: 10.1016/j.pnpbp.2020.110060. Epub 2020 Aug 7.
Ketamine was initially used as an anesthetic which could induce cognitive impairment and psychomimetic effects. In initial randomized controlled trials (RCTs) that mostly included a small sample size and were investigator-initiated, ketamine reportedly exerted antidepressant effects 1 to 2 h after a single intravenous infusion in patients with major depressive episodes, particularly treatment-resistant depression (TRD). Interest in ketamine was reported in systematic reviews and meta-analyses, however, many were primarily focused on the rapid onset of ketamine effects without equal attention to its safety and tolerability. Furthermore, several meta-analyses were based on many duplicated RCTs. The initial trends emphasized the clinical utility of ketamine as an antidepressant. The development of esketamine nasal spray by a pharmaceutical company led to an RCT with a large sample size and segmented therapeutic strategy, which provided results applicable to patients with TRD in the real-world clinical environment. However, possible effects of ketamine on cognitive function have not yet been investigated in RCTs. In numerous studies, chronic, recreational use of ketamine reportedly substantially impaired cognitive function in most domains. Although results of several human and animal studies indicated the therapeutic use of ketamine for treatment of depression did not induce cognitive impairment, this issue should be further investigated. Based on the current knowledge about ketamine, future antidepressants are expected to be glutamatergic drugs without ketamine-like adverse events (e.g., psychomimetic symptoms and cognitive impairment), but having only ketamine-like therapeutic properties (e.g., rapid antidepressants effects without time lag).
氯胺酮最初用作麻醉剂，可导致认知障碍和拟精神病效应。在最初的随机对照试验（RCT）中，大多样本量较小且由研究者发起，据报道，氯胺酮在单次静脉输注1至2小时后对重度抑郁发作患者，尤其是难治性抑郁症（TRD）患者发挥抗抑郁作用。系统评价和荟萃分析报道了对氯胺酮的兴趣，然而，许多研究主要关注氯胺酮效应的快速起效，而对其安全性和耐受性未给予同等关注。此外，一些荟萃分析基于许多重复的随机对照试验。最初的趋势强调了氯胺酮作为抗抑郁药的临床效用。一家制药公司开发的艾氯胺酮鼻喷雾剂促成了一项大样本量和分段治疗策略的随机对照试验，该试验提供了适用于真实临床环境中TRD患者的结果。然而，氯胺酮对认知功能的可能影响尚未在随机对照试验中进行研究。在众多研究中，据报道长期、娱乐性使用氯胺酮会在大多数领域严重损害认知功能。尽管一些人和动物研究结果表明，氯胺酮用于治疗抑郁症的治疗用途不会导致认知障碍，但这个问题仍应进一步研究。基于目前对氯胺酮的了解，未来的抗抑郁药有望是谷氨酸能药物，没有类似氯胺酮的不良事件（如拟精神病症状和认知障碍），但仅具有类似氯胺酮的治疗特性（如无时间延迟的快速抗抑郁作用）。
