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.

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.”

Authors: Emma Kopra, Valeria Mondelli, Carmine Pariante & Naghmeh Nikkheslat