Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy.
Andrew P. Allen, Maura Naughton, J. Dowling, Aaron M. Walsh, R. O’shea, G. D. Shorten, L. Scott, Declan M. Mcloughlin, John F Cryan, Gerard Clarke, Timothy G Dinan
Journal of Psychiatric Research February 10, 2018 DOI: 10.1016/j.jpsychires.2018.02.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression and gender-matched healthy controls |
| Interventions | Ketamine infusion Electroconvulsive therapy |
| Topics | Depression Esketamine Ketamine |
| Citations | 53 |
| Key findings | Ketamine and ECT improved depressive symptoms, but only ECT was associated with significant changes in the cortisol awakening response, while ketamine did not significantly alter measured biomarkers. |
Abstract
Current first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required. We assessed the potential impact of ketamine infusion on neurobiological drivers of kynurenine pathway metabolism in major depression (HPA axis hyperactivity, inflammation) in patients with treatment-resistant depression compared to gender-matched healthy controls. Furthermore, we assessed these biomarkers before and after electroconvulsive therapy (ECT), which is currently the gold standard for management of treatment-resistant depression. As previously demonstrated, treatment with ketamine and ECT was associated with improved depressive symptoms in patients. At baseline, waking cortisol output was greater in the ECT cohort, kynurenine was greater in the ketamine cohort, and kynurenic acid was lower in patients compared to healthy controls, although inflammatory markers (IL-6, IL-8, IL-10 or IFN-γ) were similar in patients and controls. Furthermore, in patients who responded to ECT, the cortisol awakening response was decreased following treatment. Despite a trend towards reduced kynurenine concentrations in those who responded to ketamine, ketamine was not associated with significant alterations in any of the biomarkers assessed.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |