Hannover Medical School, Hannover, Germany; Goethe University, Frankfurt/Main, Germany.
Department of Anesthesiology and Intensive Care Medicine, Pain Clinic, Hannover Medical School, Germany.
Eur Neuropsychopharmacol. 2021 Mar;44:92-104. doi: 10.1016/j.euroneuro.2021.01.005. Epub 2021 Jan 21.
Ketamine and its (S)-enantiomer show distinct psychological effects that are investigated in psychiatric research. Its antidepressant activity may depend on the extent and quality of these psychological effects which may greatly differ between the enantiomers. Previous data indicate that the (S)-ketamine isomer is a more potent anesthetic than (R)-ketamine. In contrast, in subanesthetic doses (R)-ketamine seems to elicit fewer dissociative and psychotomimetic effects compared to (S)-ketamine. In this randomized double-blind placebo-controlled trial the effects of (R/S)-ketamine and (S)-ketamine on standardized neuropsychological and psychopathological measures were compared. After an initial bolus equipotent subanesthetic doses of (R/S)- and (S)-ketamine or placebo were given by continuous intravenous infusion to three groups of 10 healthy male volunteers each (n = 30). (R/S)-Ketamine and (S)-ketamine produced significant psychopathology and neurocognitive impairment compared to placebo. No significant differences were found between (R/S)-ketamine and (S)-ketamine. (S)-Ketamine administration did not result in reduced psychopathological symptomatology compared to (R/S)-ketamine as suggested by previous studies. However, this study revealed a somewhat more "negatively experienced" psychopathology with (S)-ketamine, which opens questions about potential "protective effects" associated with the (R)-enantiomer against some psychotomimetic effects induced by the (S)-enantiomer. As the antidepressant effect of ketamine might depend on a pleasant experience of altered consciousness and perceptions and avoidance of anxiety, the ideal ketamine composition to treat depression should include (R)-ketamine. Moreover, since preclinical data indicate that (R)-ketamine is a more potent and longer acting antidepressant compared to (S)-ketamine and (R/S)-ketamine, randomized controlled trials on (R)-ketamine and comparative studies with (S)-ketamine and (R/S)-ketamine are eagerly awaited.
氯胺酮及其（S）对映体表现出不同的心理效应，这些效应在精神病学研究中得到了研究。其抗抑郁活性可能取决于这些心理效应的程度和质量，而这些效应在对映体之间可能有很大的差异。先前的数据表明，（S）-氯胺酮异构体是一种比（R）-氯胺酮更强效的麻醉剂。相比之下，在亚麻醉剂量下，（R）-氯胺酮似乎比（S）-氯胺酮引起的分离和精神病样效应更少。在这项随机、双盲、安慰剂对照试验中，比较了（R/S）-氯胺酮和（S）-氯胺酮对标准化神经心理学和精神病理学测量的影响。在三组各 10 名健康男性志愿者中，每组志愿者均先给予初始推注等效亚麻醉剂量的（R/S）-和（S）-氯胺酮或安慰剂，然后通过连续静脉输注给予（n=30）。与安慰剂相比，（R/S）-氯胺酮和（S）-氯胺酮均显著引起精神病理学和神经认知障碍。（R/S）-氯胺酮和（S）-氯胺酮之间未发现显著差异。与先前的研究表明的（S）-氯胺酮相比，（S）-氯胺酮给药并未导致精神病理学症状减轻。然而，本研究显示（S）-氯胺酮引起的精神病理学更为“负面体验”，这引发了关于与（R）-对映体相关的潜在“保护作用”的问题，这种“保护作用”可能对抗由（S）-对映体引起的一些精神病样效应。由于氯胺酮的抗抑郁作用可能依赖于改变意识和感知的愉快体验以及避免焦虑，因此治疗抑郁症的理想氯胺酮成分应包括（R）-氯胺酮。此外，由于临床前数据表明，（R）-氯胺酮比（S）-氯胺酮和（R/S）-氯胺酮具有更强的抗抑郁作用和更长的作用持续时间，因此人们急切期待着关于（R）-氯胺酮的随机对照试验以及与（S）-氯胺酮和（R/S）-氯胺酮的比较研究。
