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.
Psychiatry research
May 1, 2024
Balwinder Singh, Sagar V Parikh, Jennifer L Vande Voort et al.
18 citations
In a nonrandomized, open-label clinical trial, 74 adults with treatment-resistant depression received three intravenous ketamine infusions, with an additional four infusions for those who remitted. After the acute phase, 53% (39/74) experienced remission of depression symptoms. Higher baseline language domain scores on the RBANS cognitive assessment were associated with greater odds of remission. No significant association was found between remission and baseline immediate or delayed memory, visuospatial, or attention scores. During the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. The findings suggest cognitive improvement, not deterioration, with serial ketamine administration.
Journal of affective disorders
September 15, 2025
Brandan K Penaluna, Jennifer L Vande Voort, William V Bobo et al.
4 citations
In people with treatment-resistant depression, intravenous ketamine improved symptoms across four depression subtypes: Sadness, Negative Thoughts, detachment/Interest and Activity, and Neurovegetative. After three infusions over 11 days, 53% of the 75 participants achieved remission. The Negative Thoughts subtype showed the least improvement, and the Neurovegetative subtype was the least responsive overall. Higher baseline Sadness scores were linked to lower remission rates, and a positive Sadness phenotype reduced the odds of remission (odds ratio 0.32). No meaningful sex differences in response were found by the end of treatment.
Psychiatry research
May 1, 2025
Gerard Sanacora, Brian S Barnett, Bo Hu et al.
2 citations
Patients with treatment-resistant depression who preferred ketamine over electroconvulsive therapy (ECT) were more likely to respond to treatment, regardless of which treatment they actually received. Matching patients to their preferred treatment improved response rates for ketamine but not for ECT, and reduced adverse events for ECT-treated patients. Ketamine was the more popular choice overall. The findings suggest that aligning treatment with patient preference can influence effectiveness, safety, and possibly adherence, but these effects vary by treatment modality and context.
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.