Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study.
Mu-Hong Chen, Cheng-Ta Li, Wei-Chen Lin, Chen‐jee Hong, Pei-Chi Tu, Ya-Mei Bai, Chih-Ming Cheng, Tung-Ping Su
Psychiatry Research November 2018 DOI: 10.1016/j.psychres.2018.08.078 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 71 |
| Population | Patients with treatment-resistant depression |
| Interventions | Ketamine Normal saline |
| Dose | 0.5 mg/kg ketamine, 0.2 mg/kg ketamine |
| Duration | Assessments at baseline, 40 min, 240 min, Day 3, and Day 7 postinfusion |
| Measures | Montgomery-Åsberg Depression Rating Scale (MADRS), C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α |
| Topics | Depression Ketamine Esketamine |
| Keywords | Crp Cytokines Il-6 Tnf-α |
| Key findings | Log-transformed IL-6 and TNF-alpha levels changed significantly over time after infusion. In the 0.5 mg/kg ketamine group, the decrease in TNF-alpha from baseline to 40 minutes was positively correlated with improvement in MADRS depression scores over time. The authors propose that rapid suppression of proinflammatory cytokines may contribute to ketamine's rapid antidepressant effect. |
Abstract
Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized into three groups according to the treatment received: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and normal saline infusion. Proinflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were examined at baseline and at 40 min, 240 min, Day 3, and Day 7 postinfusion. Montgomery-Åsberg Depression Rating Scale (MADRS) was assessed for depressive symptoms across time. Log-transformed IL-6 and TNF-α levels differed significantly over time. The decrease in TNF-α between baseline and 40 min postinfusion was positively correlated with a decrease in MADRS scores across time in the 0.5 mg/kg ketamine group. This is the first clinical study to support a positive correlation between changes in cytokine levels after ketamine infusion and improvements in depressive symptoms with TRD. The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
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- A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Psychopharmacology Bulletin March 4, 2024
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. Journal of Affective Disorders November 1, 2020
- An update on ketamine and its two enantiomers as rapid-acting antidepressants Expert Review of Neurotherapeutics December 4, 2018
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Cites 6
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Translational Psychiatry March 21, 2017
- Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology December 2017
- Ketamine Alleviates Depressive-Like Behaviors via Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice. Biological and Pharmaceutical Bulletin August 1, 2017
- Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action. The Journal of Clinical Psychiatry April 2017
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