Martinotti Giovanni, Chiappini Stefania, Pettorruso Mauro, Mosca Alessio, Miuli Andrea, Di Carlo Francesco, D'Andrea Giacomo, Collevecchio Roberta, Di Muzio Ilenia, Sensi Stefano L, Di Giannantonio Massimo
Department of Neurosciences, Imaging and Clinical Sciences, Università degli Studi G. D'Annunzio, 66100 Chieti-Pescara, Italy.
Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hertfordshire AL10 9AB, UK.
Brain Sci. 2021 Jun 27;11(7):856. doi: 10.3390/brainsci11070856.
The obsessive-compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive-compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords ("ketamine" or "esketamine") AND ("obsessive" OR "compulsive" OR "OCD" OR "SUD" OR "substance use disorder" OR "addiction" OR "craving" OR "eating" OR "anorexia") NOT review NOT animal NOT "in vitro", on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine's use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness.
强迫谱系障碍是指源自多个诊断类别的疾病，这些疾病具有与强迫症（OCD）相关的核心特征，如强迫观念、强迫行为和焦虑。包括这些特征的疾病可根据症状焦点进行分组，例如对身体的过度关注（即饮食失调，ED）或冲动控制（即物质使用障碍，SUD），并且它们在现象学、病因学、病理生理学、患者特征和临床结果方面表现出有趣的相似性。在过去十年积累的数十项小型研究中，非竞争性N-甲基-D-天冬氨酸受体（NMDAr）拮抗剂氯胺酮已被证明在治疗难治性抑郁症、创伤后应激障碍和强迫症患者方面产生显著效果，并且它在治疗SUD和ED方面似乎也很有前景。然而，尽管有许多小型研究，但仍缺乏其用于治疗强迫谱系障碍和成瘾的益处的确凿证据。因此，这篇观点文章的目的是研究氯胺酮和艾氯胺酮在治疗OCD、ED和SUD方面的潜力，这些疾病都涉及反复出现的侵入性思维并产生相关的强迫行为。本文提供了关于氯胺酮和艾氯胺酮药理作用机制以及它们相对于当前治疗方法的治疗优势的全面且更新的文献综述。使用以下关键词（“氯胺酮”或“艾氯胺酮”）AND（“强迫观念的”或“强迫行为的”或“OCD”或“SUD”或“物质使用障碍”或“成瘾”或“渴望”或“饮食”或“厌食症”）NOT综述NOT动物NOT“体外”，在PubMed、Cochrane图书馆和科学网在线数据库上进行了电子检索。该综述是根据系统评价和荟萃分析的首选报告项目（PRISMA）指南进行的。氯胺酮在SUD、ED和OCD中的使用和疗效得到谷氨酸能神经传递失调的支持，这在这些疾病中起重要作用。氯胺酮的使用正在增加，初步数据令人乐观。需要进一步研究以更好地阐明与氯胺酮和艾氯胺酮在SUD、ED和OCD中的使用相关的许多未知因素，并了解它们的长期有效性。
