Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review
This literature review (2021) explores ketamine's anti-inflammatory properties and tryptophan-kynurenine (KYN) pathway in patients with unipolar and bipolar depression as well as in animal models of depression. It found that ketamine induces anti-inflammatory effects in at least a proportion of patients with depression and decreased activation of the KYN pathway's neurotoxic arm.
Authors
- Kopra, E.
- Mondelli, V.
- Pariante, C.
Published
Abstract
Background
Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest.
Aim
This systematic review examined the effect of ketamine on inflammatory markers and TRP-kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression.
Methods
MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020).
Results
Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway.
Conclusion
Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.
Research Summary of 'Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review'
Introduction
Major depressive disorder and bipolar depression remain major causes of disability, with a substantial proportion of patients not responding adequately to conventional monoaminergic antidepressants and with slow onset of therapeutic effect. Ketamine, an NMDA receptor antagonist first used as an anaesthetic, has emerged since 2000 as a rapid-acting antidepressant with high response rates reported in treatment-resistant samples and effects that can appear within hours. Interest has grown in ketamine's anti-inflammatory properties because inflammation is implicated in depression and may act via the tryptophan (TRP)–kynurenine (KYN) pathway: pro-inflammatory cytokines activate indoleamine 2,3-dioxygenase (IDO) and KMO, shifting TRP metabolism towards neurotoxic metabolites such as quinolinic acid (QUIN) and 3-hydroxykynurenine (3-HK), while kynurenic acid (KynA) is associated with neuroprotection. Kopra and colleagues set out to systematically review the evidence that ketamine alters inflammatory markers and TRP–KYN pathway metabolites in patients with unipolar or bipolar depression and in animal models of depression. The review aimed to synthesise clinical and preclinical findings to clarify whether ketamine produces anti-inflammatory and neuroprotective metabolic effects that could help explain its antidepressant action and to identify gaps for future research.
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Study Details
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- APA Citation
Kopra, E., Mondelli, V., Pariante, C., & Nikkheslat, N. (2021). Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review. Journal of Psychopharmacology, 35(8), 934-945. https://doi.org/10.1177/02698811211026426
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Cited By (2)
Papers in Blossom that reference this study
Meshkat, S., Cao, B., Teopiz, K. M. et al. · Journal of Affective Disorders (2023)
Nikkheslat, N. · Brain Behavior and Immunity - Health (2021)
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