The safety of repeated ketamine dosing in paediatrics: A systematic review

Background:Ketamine is emerging as an effective, rapidly acting antidepressant in adult research. Hypothetical concerns about its long-term safety and impact on the developing brain are limiting its research in children. However, a wealth of paediatric safety and dosing data exists for ketamine, given its extensive use globally as an anaesthetic, analgesic and sedative agent. Aims:To evaluate the safety of repeat dosing of ketamine in children. Methods:A systematic search of EMBASE, MEDLINE, PsycINFO, Cochrane Library and PubMed from inception to 13 April 2023 was conducted. Included studies were those reporting adverse events when ketamine was given repeatedly to children aged 5-18, for any condition. No language restrictions were applied. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and Joanna Briggs Institute Critical Appraisal Tools Checklist for study quality assessment were used. The review process was performed independently by two reviewers. Results:Five observational studies (87 patients) were included. The maximum number of doses per patient was 42, over a maximum of 4 months. There were no serious adverse events. There was no evidence of needing higher doses with time to indicate tolerance. The longest follow-up period was 6 months. There were no long-term consequences (including neurocognitive) reported within this time frame. Conclusions:These results suggest that, despite methodological limitations of the studies, ketamine is well tolerated and safe for use in children, even when given repeatedly in regimens analogous to those used for the treatment of depression in adults. This finding supports the expansion of research into the use of ketamine as a novel antidepressant in children.