Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review
Emma I Kopra, Valeria Mondelli, Carmine M. Pariante, N. Nikkheslat
Journal of Psychopharmacology June 26, 2021 DOI: 10.1177/02698811211026426 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Patients with unipolar and bipolar depression and animal models of depression |
| Topics | Depression Esketamine Ketamine |
| Citations | 89 |
| Key findings | Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients, with rodent studies showing strong support for decreases in pro-inflammatory cytokines and human studies showing less robust but consistent decreases in peripheral inflammation. |
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.