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Oral ketamine may offer a solution to the ketamine conundrum

Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with addition...

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Autores principales: Dutton, Megan, Can, Adem T., Lagopoulos, Jim, Hermens, Daniel F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640543/
https://www.ncbi.nlm.nih.gov/pubmed/37882811
http://dx.doi.org/10.1007/s00213-023-06480-x
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author Dutton, Megan
Can, Adem T.
Lagopoulos, Jim
Hermens, Daniel F.
author_facet Dutton, Megan
Can, Adem T.
Lagopoulos, Jim
Hermens, Daniel F.
author_sort Dutton, Megan
collection PubMed
description Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.
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spelling pubmed-106405432023-11-14 Oral ketamine may offer a solution to the ketamine conundrum Dutton, Megan Can, Adem T. Lagopoulos, Jim Hermens, Daniel F. Psychopharmacology (Berl) Review Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review. Springer Berlin Heidelberg 2023-10-26 2023 /pmc/articles/PMC10640543/ /pubmed/37882811 http://dx.doi.org/10.1007/s00213-023-06480-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Dutton, Megan
Can, Adem T.
Lagopoulos, Jim
Hermens, Daniel F.
Oral ketamine may offer a solution to the ketamine conundrum
title Oral ketamine may offer a solution to the ketamine conundrum
title_full Oral ketamine may offer a solution to the ketamine conundrum
title_fullStr Oral ketamine may offer a solution to the ketamine conundrum
title_full_unstemmed Oral ketamine may offer a solution to the ketamine conundrum
title_short Oral ketamine may offer a solution to the ketamine conundrum
title_sort oral ketamine may offer a solution to the ketamine conundrum
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640543/
https://www.ncbi.nlm.nih.gov/pubmed/37882811
http://dx.doi.org/10.1007/s00213-023-06480-x
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