A Scoping Review of the Use of Arketamine in Humans
Creators: name: LEAL, GUSTAVO CARNEIRO GOMES
Publisher: name: Open Science Framework
Year: 2023
Subjects: subject: Medicine and Health Sciences
subject: Pharmacy and Pharmaceutical Sciences
subject: Mental Disorders
subject: Medical Pharmacology
subject: Medical Sciences
subject: Neurosciences
subject: FOS: Clinical medicine
subject: Psychiatry and Psychology
subject: arketamine
subject: R-ketamine
subject: ketamine
subject: NMDA antagonist

description: Background: Arketamine, an enantiomer of ketamine, has emerged as a potential alternative for treating depression and other psychiatric disorders. While extensive research has been conducted on racemic ketamine and the other enantiomer, esketamine, there is a notable lack of studies exploring the use of arketamine in humans. This scoping review aims to address this gap by conducting a comprehensive analysis of published and gray literature on arketamine use in humans, following the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Objective: The objective of this scoping review is to provide an extensive historical overview of arketamine use in humans, encompassing its effects, outcomes, adverse events, and potential indications. Methods: Our review will employ a rigorous approach, incorporating various sources of evidence to ensure a comprehensive and reliable analysis. To achieve this, we will conduct a systematic search utilizing the PRISMA-ScR guidelines. We will begin by searching published literature, encompassing peer-reviewed articles, but also gray literature. The electronic databases PubMed and Embase will serve as our primary sources for published literature. Within the Embase database, we will also search for conference proceedings and to identify relevant ongoing or unpublished clinical trials, we will search the ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, by this way covering important sources of what is considered gray literature. Furthermore, to ensure a comprehensive examination of the topic, we will conduct a thorough review of the reference lists of all included documents. This approach will help us identify any additional relevant materials that might not have been captured through our previous searches. Our search terms will primarily consist of: arketamine OR R-ketamine OR "(R)-ketamine" OR "R(-) ketamine," tailored to the search mechanisms of each respective database. We will include all studies, case reports, and clinical trials reporting on the use of arketamine in humans, regardless of the indication. Epidemiological and preclinical studies will be excluded. Two independent reviewers will be involved in the screening and selection process of studies. Both reviewers will independently assess the titles and abstracts of identified articles to determine their eligibility for inclusion. Any discrepancies in the selection were resolved through discussion and consensus.The following "PCC'' framework provides a detailed outline of our inclusion criteria: - Population: Human beings of any age, sex, or clinical condition. - Concept: Any information on the effects of arketamine administration, including but not limited to: - Physiological effects - Pharmacodynamics and pharmacokinetics - Therapeutic efficacy for physical or psychological symptoms - Adverse effects and safety data - Context: No restrictions. - Studies may originate from any geographic location and be published in any language. We will encompass all available literature, such as primary research studies, systematic reviews, meta-analyses, letters, websites, and poster presentations. - If possible, we will attempt to contact the research teams of clinical trials registries for any unpublished data. Data Extraction: We will extract the following study information from each included study: author(s), year of publication, origin/country of origin, aims/purpose, study population and sample size (if applicable), methodology/methods, intervention type/duration, comparator, outcome measures (if applicable), outcomes and details of these (e.g., measurement methods) (if applicable), and key findings relevant to the scoping review question. Both reviewers will independently extract the data and any discrepancies will be resolved through discussion and consensus. Data Analysis: A descriptive approach, following PRISMA-ScR guidelines, will be utilized to summarize the findings of the included studies. We will present the data using tables and charts, accompanied by a narrative synthesis of the results. Ethics and Dissemination: This study does not involve human participants or data. Before commencing the review, we will publish the protocol on https://osf.io/, adhering to PRISMA-ScR recommendation. The results of this scoping review will be disseminated through a peer-reviewed publication and presented at conferences. Additionally, we will make the results available on https://osf.io/, in accordance with PRISMA-ScR guidelines. Conclusion: This scoping review will offer a comprehensive overview of arketamine use in humans, including its effects, outcomes, adverse events, and potential indications, while adhering to PRISMA-ScR guidelines. The findings of this study may provide valuable insights for future research and clinical practice concerning the use of arketamine. References: Zhang JC, Li SX, Hashimoto K. R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav. 2014;116:137-141. doi:10.1016/j.pbb.2013.11.033 Zhang JC, Yao W, Hashimoto K. Arketamine, a new rapid-acting antidepressant: A historical review and future directions. Neuropharmacology. 2022;218:109219. doi:10.1016/j.neuropharm.2022.109219 Leal GC, Souza-Marques B, Mello RP, et al. Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study. J Affect Disord. 2023;330:7-15. doi:10.1016/j.jad.2023.02.151 Leal GC, Bandeira ID, Correia-Melo FS, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci. 2021;271(3):577-582. doi:10.1007/s00406-020-01110-5 Tricco, A.C. et al. (2018) ‘Prisma extension for scoping reviews (PRISMA-SCR): Checklist and explanation’, Annals of Internal Medicine, 169(7), pp. 467–473. doi:10.7326/m18-0850.