key: cord-1050721-is7gql2m
authors: Akinosoglou, Karolina; Gogos, Athanasios; Papageorgiou, Charalambos; Angelopoulos, Elias; Gogos, Charalambos
title: Ketamine in COVID‐19 patients: Thinking out of the box
date: 2020-12-01
journal: J Med Virol
DOI: 10.1002/jmv.26681
sha: ea7b779107483f0e71bb27de81002d70fa5a3fb5
doc_id: 1050721
cord_uid: is7gql2m

COVID-19, identified as the disease caused by SARS-CoV-2, was recognized as a public health emergency by World Health Organization, and declared a pandemic on March 11, 2020. This article is protected by copyright. All rights reserved.

Ketamine, on the other hand, has been long used in the management of treatment-resistant-depression, as a nonselective NMDA receptor antagonist, utilising both its intranasal and intravenous form, even though the latter showing better efficacy. [5] [6] [7] Recent data have come to show that, it effectively treats both typical/melancholic and atypical depressive symptoms, even though, the exact mechanism underlying its efficacy remains unclear. 5 Previous animal studies have unveiled that, ketamine generates an anti-inflammatory effect that could contribute to its antidepressant action. 8 After all, lowgrade inflammation, characterized by an increase in serum proinflammatory cytokines, including IL-6, IL-1β, CRP, and so forth, may play a role in depression pathogenesis and represents a good predictor of clinical response. 8, 9 Apparently, patients with an activated inflammatory state, need a step up to dopaminergic or glutaminergic drug like ketamine, to avoid aggravated alteration in neurotransmitter metabolism, 9 that blunts response to first-line drugs. In clinical models, ketamine downregulates the level of several inflammatory cytokines, including IL-6, while changes at their level significantly correlate with symptom improvement on day 13. 8 What the exact path and timing from micro-molecular changes to symptom improvement remains under investigation. 8 Further evidence shows that, it may actually exert both its beneficial anti-depressant and toxic effects via the same IL-6 blockade in a dose-dependent manner; even though, exact timing remains elusive.

Even though, the need for more extensive prospective studies for the establishment of causality relationships and safer conclusions to be drawn is pivotal, the role of antidepressants and especially ketamine is worth to explore in COVID-19 with presenting or the previous history of mental disease and/or depressive symptoms.

Given its suggested role in the treatment of certain mental health disorders and its anti-inflammatory effect, the role of ketamine in SARS-Cov-2 patients presenting with specific neuropsychiatric symptoms including depression should be put into trial. It would be interesting to explore whether, presenting symptoms and concurrent administration of neuropsychiatric regimens, including ketamine could have an impact on outcome in this cohort of patients having a history of or presenting with the neuropsychiatric disease, potentially offering an alternative to high-cost tocilizumab in the future immunomodulatory interventions. Of note, as one might expect from previous experience, its cardiovascular and neurological side effects, could limit its utility. Nonetheless, even though, the intravenous form is better used in hospital environment, its intranasal counterpart (esketamine), avoiding systemic toxicity and allowing for administration of lower dosages, could represent a safe regimen for controlled community use. 6 Amid results from clinical trials and drug repurposing, we should consider the possibility that COVID-19 patients with increased levels of IL-6 and/or history or presentation of depressive symptoms could represent candidates of a new "Special K" population.

Spectrum of neuropsychiatric manifestations in COVID-19

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Immunology of COVID-19: current state of the science

Complex immune dysregulation in COVID-19 patients with severe respiratory failure

The effects of ketamine on typical and atypical depressive symptoms

Rapid-acting antidepressant ketamine, its metabolites and other candidates: a historical overview and future perspective

Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

lLow-grade inflammation as a predictor of antidepressant and antiinflammatory therapy response in MDD patients: a systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME Consortium