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Harm related to recreational ketamine use and its relevance for the clinical use of ketamine. A systematic review and comparison study

Jan Van Amsterdam, Wim van den Brink

Expert Opinion on Drug Safety June 26, 2021 DOI: 10.1080/14740338.2021.1949454 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Population Heavy recreational (non-medical) ketamine users and patients treated with ketamine
Intervention Ketamine
Topics Esketamine Ketamine
Citations 42
Key findings The authors conclude that ketamine treatment is not associated with ketamine dependency or serious adverse events, whereas heavy recreational use, with over 90 times greater cumulative exposure, was often dose-dependently associated with dependency, cognitive and mental disorders, and gastrointestinal and urinary symptoms that resolved upon marked reduction of use. They caution that long-term clinical data are lacking.

Abstract

BACKGROUNDS: Ketamine is a dissociative anesthetic that is currently considered for several new indications.

Aim: To deduce the safety of long-term ketamine treatment using the harm of heavy recreational (non-medical) ketamine use as a proxy for maximal possible harm of ketamine treatment.

Methods: Systematic literature review according to PRISMA guidelines to identify controlled studies on ketamine-related harm in heavy recreational ketamine users. Results were compared with serious adverse events (SAEs) in patients treated with ketamine according to three systematic reviews considering dosing regimen and cumulative dose.

Results: The systematic search yielded 25 studies. Heavy recreational ketamine use can escalate to ketamine dependency and was often dose-dependently associated with other SAEs, including cognitive and mental disorders, and gastrointestinal and urinary tract symptoms, which disappeared upon marked reduction of ketamine use. Heavy ketamine users have a much higher cumulative exposure to ketamine than ketamine treated patients (>90 times), which may explain why SAEs in the clinical context are mostly mild and reversible and why ketamine dependence was not reported in these patients.

Conclusion: Treatment of patients with ketamine is not associated with ketamine dependency or SAEs. However, caution is needed since data on long-term clinical ketamine use with a long-term follow-up is lacking.

Comparable studies

Other systematic reviews and meta-analyses on ketamine, most cited first.

Study Year Design Participants
The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline 2017 Systematic review and individual participant data meta-analysis n = 167
Ketamine use: a review Ketamine users 2011 Systematic review
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries 2004 Systematic review n = 2,839
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review

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