The lancet. Psychiatry
October 1, 2023
Gustavo C Medeiros, Malcolm Matheson, Isabella Demo et al.
38 citations
A systematic review of 69 neuroimaging studies (1751 participants) found no well-replicated biomarker for ketamine's antidepressant response, but identified several promising candidates. Response to ketamine was associated with post-treatment increases in gamma power in frontoparietal regions, increased functional connectivity within the prefrontal cortex, and increased functional activation of the striatum. The review highlights substantial methodological heterogeneity across studies and calls for further investigation of these biomarkers.
Translational psychiatry
November 29, 2024
Gustavo C Medeiros, Isabella Demo, Fernando S Goes et al.
32 citations
Treatment-resistant depression accounts for a large share of the burden of major depressive disorder. Intravenous ketamine and intranasal esketamine are rapid-acting antidepressants that can effectively treat this condition, but response varies. Reliable predictors of response are urgently needed. Clinical predictors of a robust response to ketamine include a family history of alcohol use disorder and a history of childhood trauma. A promising brain-based biomarker is an increase in gamma power in frontoparietal regions measured by EEG. Blood-based biomarkers have shown limited usefulness, with small-effect increases in BDNF being the most consistent indicator. Dissociative symptoms during treatment are not typically associated with response. Most predictors have modest effect sizes, so multivariate models will be needed.
Journal of affective disorders
March 15, 2025
Polymnia Georgiou, Cristan A Farmer, Gustavo C Medeiros et al.
24 citations
Baseline levels of stress-related hormones (CRF, ACTH, and cortisol) did not significantly influence how well ketamine worked as an antidepressant in people with treatment-resistant depression. However, higher levels of ACTH and CRF were associated with longer overall duration of depressive episodes, suggesting these hormones might serve as biomarkers for chronic depression. Additionally, people who developed depression at a younger age tended to have more severe depressive symptoms, indicating that earlier onset may lead to greater cumulative stress on the brain and body. The study involved 42 participants in a randomized, placebo-controlled, crossover trial.
Neuron
November 19, 2025
Kyle A Brown, Musa I Ajibola, Gustavo C Medeiros et al.
6 citations
Ketamine, a rapid-acting antidepressant, relieves depression symptoms for days after the drug leaves the body, and repeated doses produce longer-lasting effects. This review proposes that ketamine and similar drugs act as synaptic primers, making synapses more responsive to subsequent doses, a process derived from metaplasticity. The indirect relationship between ketamine's pharmacokinetics and sustained pharmacodynamics defines a dosing model called primer pharmacology, which can optimize therapeutic outcomes. The plasticity mechanisms engaged by antidepressants overlap with those triggered by stress and psychotherapy, suggesting combined treatment strategies. Emerging primers like psilocybin also fit this framework, offering a model to guide clinical and translational psychiatry.
Biological psychiatry global open science
July 1, 2025
Stephen A Murata, Zachary B Madaj, Colt D Capan et al.
1 citation
Higher baseline levels of anthranilic acid (AA), a metabolite in the kynurenine pathway, predicted remission in patients with treatment-resistant depression receiving intravenous ketamine. In an open-label trial of 74 patients, 52% achieved remission after three infusions. Composite ratios of AA to intercellular adhesion molecule-1 and AA to tryptophan improved predictive accuracy over AA alone. The findings suggest that immunometabolic biomarkers could guide personalized ketamine treatment.