Antidepressant Effect of Ketamine on Inflammation‐Mediated Cytokine Dysregulation in Adults with Treatment‐Resistant Depression: Rapid Systematic Review
Shiryn D. Sukhram, Grozdena Yilmaz, Jianying Gu
Oxidative Medicine and Cellular Longevity 2022 DOI: 10.1155/2022/1061274 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression (TRD) |
| Intervention | Ketamine infusion |
| Topics | Anxiety Ketamine Depression Esketamine |
| Keywords | Antidepressant Depression economics Inflammation Cytokine Meta-analysis Pharmacology Immunology |
| Citations | 26 |
| Key findings | Ketamine infusion may reduce depressive symptoms in TRD patients, with a 56% response rate based on MADRS and HAM-D scores, but its rapid antidepressant effect remains inconsistent. |
Abstract
Background . Major depressive disorder (MDD) and treatment‐resistant depression (TRD) represent a global source of societal and health burden. To advise proper management of inflammation‐related depression among TRD patients, it is important to identify therapeutic clinical treatments. A key factor is related to proinflammatory cytokines such as interleukin‐ (IL‐) 1 β , IL‐6, and tumor necrosis factor‐ (TNF‐) α which have been implicated in the pathogenesis of depressive symptoms in MDD patients. Ketamine may provide an anti‐inflammatory therapeutic strategy by targeting proinflammatory pathways associated with depressive disorders, which may be exacerbated in the ageing population with TRD. Objective . Despite a burgeoning body of literature demonstrating that inflammation is linked to TRD, there is still a lack of comprehensive research on the relationship between proinflammatory biomarkers and ketamine’s antidepressant effect on TRD patients. Method . The Cochrane Library and PubMed/MEDLINE databases were systematically searched from inception up to February 1, 2022, adopting broad inclusion criteria to assess clinical topics related to the impact of ketamine on inflammatory cytokines in TRD patients. The present work is in compliance with the World Health Organization Rapid Review Guide. Results . Five out of the seven studies examined in this review show that ketamine infusion may reduce depressive symptoms with a quick start of effect on TRD patients. Based on the Montgomery‐Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM‐D) scores, the overall response rate for ketamine was 56%; that is, 56% of those treated with ketamine had MADRS/HAM‐D scores decreased by at least 50%. Conclusions . While the anti‐inflammatory effects of ketamine modulate specific proinflammatory cytokines, its rapid antidepressant effect on TRD patients remains inconsistent. However, our study findings can provide a reliable basis for future research on how to improve systemic inflammatory immune disorders and mental health. We suggest that ketamine infusion may be part of a comprehensive treatment approach in TRD patients with elevated levels of depression‐specific inflammatory biomarkers.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for anxiety, most cited first.
Citations in the library
Cited by 8
- Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects? Molecular Psychiatry September 1, 2024
- Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway. The International Journal of Neuropsychopharmacology October 1, 2024
- Assessment of complement cascade components in patients with major depressive disorder. Brain, Behavior, and Immunity July 1, 2025
- Modulation of ER Stress and Inflammation by S-Ketamine, R-Ketamine, and Their Metabolites in Human Microglial Cells: Insights into Novel Targets for Depression Therapy. Cells June 3, 2025
- Ketamine for Adults With Treatment-Resistant Depression or Posttraumatic Stress Disorder: A 2023 Update Canadian Journal of Health Technologies January 17, 2024
and 3 more in the library
Cites 14
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review Therapeutic Advances in Chronic Disease April 13, 2015
- Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Translational Psychiatry March 21, 2017
- Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review Journal of Psychopharmacology June 26, 2021
and 9 more in the library