Abstract
RationaleKetamine is the first widely used substance with rapid-onset antidepressant action. However, there are uncertainties regarding its potential urothelial toxicity, particularly after repeated application. In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported. It is assumed that ketamine interacts with bladder urothelial cells and induces apoptosis.ObjectivesThis study aimed to assess whether single or repeated doses of esketamine used in an antidepressant indication are associated with urinary toxicity.MethodsWe included male and female inpatients with a current episode of depression and a diagnosis of recurrent depressive disorder, bipolar disorder or schizoaffective disorder according to ICD-10 criteria (n = 25). The esketamine treatment schedule involved a maximum of 3× weekly dosing at 0.25–0.5 mg/kg i.v. or s.c. The primary outcome was the change in urine toxicity markers (leukocytes, erythrocytes, protein and free haemoglobin). Description of demographic, clinical and laboratory data was conducted using means, standard deviations, frequencies and percentages. Changes in urinary toxicity markers over time were evaluated using linear mixed models with gender as a covariate.ResultsThe participants received an average of 11.4 (SD 8) esketamine treatments, and an average number of 11.2 (SD 8) urine samples were analysed over the course of treatment. Neither urinary leukocyte concentration (F(20; 3.0) = 3.1; p = 0.2) nor erythrocyte concentration (F(20;2.2) = 4.1; p = 0.2) showed a significant trend towards increase during the course of esketamine treatment. Similarly, free haemoglobin and protein concentrations, which were analysed descriptively, did not display a rise during treatment. There was a significant improvement in depression ratings after esketamine treatment (p < 0.001).ConclusionsThis study is, to the best of our knowledge, the first to focus on urothelial toxicity of esketamine used in antidepressant indication and dose. The results indicate that the use of single or repeated doses of esketamine is unlikely to cause urothelial toxicity. The results are in need of confirmation as sample size was small.
Highlights
Ketamine has been successfully used in anaesthesia and emergency medicine as a rapid-onset and short-duration analgesicElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.and narcotic substance since the 1960s
Patients who had received at least one treatment with esketamine in an antidepressant indication and dose (0.25–0.5 mg/kg body weight) during the period of March 2017–June 2019 were included in the analysis
The esketamine treatment schedule involved a maximum of 3× weekly dosing (Ritter et al 2020)
Summary
Ketamine has been successfully used in anaesthesia and emergency medicine as a rapid-onset and short-duration analgesic. Ketamine and its S-isomer esketamine, which is assumed to have a greater analgesic and anaesthetic activity with less psychotomimetic effects than the racemic mixture or its R-isomer (Muller et al 2016), are the first widely used substances with rapid-onset. Their efficacy in subanaesthetic doses has been established in numerous studies (Romeo et al 2015; Muller et al 2016) including both single-dose (Berman et al, 2000; Zarate et al 2006) and repeated-dose application (Rasmussen et al 2013; Murrough et al 2013b; Shiroma et al 2014). Doubts regarding its potential urothelial toxicity, after repeated application, remain (Short et al 2018)
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