Abstract
Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability.Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool.Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5–1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects.Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted.Systematic Review Registration: CRD42019137434
Highlights
IntroductionInterest in ketamine, its racemic compound and enantiomers [i.e., S-ketamine (esketamine) (6) and Rketamine (arketamine) (7)], has increased in the literature since 2016
Ketamine has been studied and used for psychiatric purposes for over 20 years (1)
Its rapid and robust antidepressant effect has been reproduced across numerous studies by significantly decreasing the severity of depression, achieving substantial rates of response and remission even for patients that were nonresponsive to previous treatments (1–5)
Summary
Interest in ketamine, its racemic compound and enantiomers [i.e., S-ketamine (esketamine) (6) and Rketamine (arketamine) (7)], has increased in the literature since 2016. This led to FDA approval of intranasal (IN) esketamine for treating depression in 2019 (8, 9).The pharmacokinetic features of ketamine allow for its administration by numerous routes including intravenous (IV) (1–5), subcutaneous (SC) (10), intranasal (IN) (8, 9), oral (11), sublingual (12), and intramuscular (IM) (13). Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use relevant in developing countries. We provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability
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