Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, Toronto, ON, Canada; Department of Human Biology, University of Toronto, Toronto, ON, Canada.
J Psychiatr Res. 2022 Jul;151:476-496. doi: 10.1016/j.jpsychires.2022.04.035. Epub 2022 May 10.
While ketamine has been used clinically over the past decades, it has only been recently shown to be a promising therapy for treatment-resistant depression (TRD). However, ketamine and related dissociative agents may also be misused recreationally, creating significant concerns for abuse liability when prescribed for depression. Although the abuse potential of ketamine is widely recognized, there is limited evidence on the differential abuse liability of ketamine enantiomers, (S)-ketamine and (R)-ketamine. The current scoping review aims to summarize the extant literature on the abuse liability of (R,S)-ketamine and the enantiomers. A systematic search was conducted on the Embase, Medline, and APA PsycInfo databases from 1947 to July 29, 2021. Clinical and preclinical studies that assessed the abuse potential of (R,S)-ketamine, (S)-ketamine, and (R)-ketamine were screened and assessed for eligibility by two independent reviewers. A total of 65 eligible studies were identified; 55 were preclinical studies and 10 were clinical studies. Only 4 preclinical studies evaluated the abuse liability of ketamine enantiomers. Available preclinical evidence suggests that (R,S)-ketamine and (S)-ketamine have greater risk for abuse compared to (R)-ketamine. (R)-ketamine, at the antidepressant-relevant doses in rodents, appears to be safe with minimal liability for abuse. Although the abuse potential of (R,S)-ketamine is well-established in animals, limited clinical studies indicate that single or repeated ketamine administrations in professionally controlled settings did not result in misuse, dependence, diversion and/or gateway activity in patients with TRD. However, most clinical studies were retrospective and did not systematically evaluate the abuse liability of ketamine via validated psychological scales/questionnaires. Future randomized controlled trials are warranted to ascertain the abuse liability of racemic, (S)- and (R)-ketamine in TRD population, especially among patients with comorbid substance use disorders.
虽然氯胺酮在过去几十年中已在临床上使用，但最近才被证明是治疗抵抗性抑郁症 (TRD) 的一种有前途的疗法。然而，氯胺酮和相关的分离剂也可能被滥用于娱乐，当用于治疗抑郁症时，会引起对滥用倾向的重大关注。尽管氯胺酮的滥用潜力已得到广泛认可，但关于氯胺酮对映异构体（S）-氯胺酮和（R）-氯胺酮的差异滥用倾向的证据有限。目前的范围综述旨在总结关于（R，S）-氯胺酮和对映异构体滥用倾向的现有文献。从 1947 年到 2021 年 7 月 29 日，在 Embase、Medline 和 APA PsycInfo 数据库上进行了系统搜索。通过两名独立审查员筛选并评估了评估（R，S）-氯胺酮、（S）-氯胺酮和（R）-氯胺酮滥用潜力的临床和临床前研究的资格。共确定了 65 项合格研究；其中 55 项为临床前研究，10 项为临床研究。只有 4 项临床前研究评估了氯胺酮对映异构体的滥用倾向。现有临床前证据表明，（R，S）-氯胺酮和（S）-氯胺酮的滥用风险大于（R）-氯胺酮。在啮齿动物中，与抗抑郁相关剂量的（R）-氯胺酮似乎安全，滥用的可能性很小。尽管（R，S）-氯胺酮在动物中的滥用潜力已得到充分确立，但有限的临床研究表明，在专业控制的环境中单次或重复给予氯胺酮不会导致 TRD 患者出现误用、依赖、转移和/或门户活动。然而，大多数临床研究是回顾性的，并未通过经过验证的心理量表/问卷系统地评估氯胺酮的滥用倾向。需要进行随机对照试验以确定 TRD 人群中（R，S）-氯胺酮、（S）-氯胺酮和（R）-氯胺酮的滥用倾向，特别是在合并物质使用障碍的患者中。
