Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 27, 2026
Chris H. Miller, Angela Hickman, Caitlin Baten et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a novel treatment for major depressive disorder (MDD) and treatment-resistant depression (TRD). Its antidepressant properties were discovered serendipitously, leading to FDA approval for TRD and MDD with suicidal ideation. The drug acts primarily as an NMDA receptor antagonist, triggering a paradoxical AMPA-mediated glutamate surge that promotes synaptogenesis and neuroplasticity. Intravenous ketamine and intranasal esketamine differ in dosing, bioavailability, and onset. Common adverse effects include dissociation, sedation, and hypertension. Efficacy studies show mixed-to-positive results, with non-inferiority to established treatments like electroconvulsive therapy. Future research aims to develop predictive markers for personalized medicine.
Biological psychiatry. Cognitive neuroscience and neuroimaging
January 13, 2026
Caitlin Baten, Gladys Zamora, Amanda M Klassen et al.
A meta-analysis of 135 fMRI studies involving 6,391 participants found that youth and adults with major depressive disorder (MDD) show different patterns of brain activation during tasks. Compared to adults with MDD, youth with MDD had distinct activation differences in the subgenual anterior cingulate cortex (sgACC) and dorsolateral prefrontal cortex (dlPFC). After controlling for illness duration, youth showed less activation than adults with shorter-duration MDD in regions like the sgACC. Among adults, those with longer-duration MDD showed less activation in the dlPFC compared to those with shorter-duration MDD. These results suggest that both age and length of illness matter for understanding brain changes in depression.
European Psychiatry
April 1, 2024
A. M. Klassen, C.t.m. Baten, J. H. Shepherd et al.
Repeated-dose intravenous ketamine is an effective rapid-acting treatment for treatment-resistant depression. In a large-scale analysis of 1,182 participants across 51 primary studies, intravenous ketamine produced statistically significant reductions in depression symptoms compared to placebo and other control conditions, as measured by standardized clinician and self-report scales. The findings provide quantitative support for ketamine's effectiveness in treatment-resistant depression and highlight variations in treatment parameters across the literature.
European Psychiatry
April 1, 2024
J. H. Shepherd, A. Hickman, C.t.m. Baten et al.
Acute ketamine administration alters neural activation in multiple cortical and subcortical regions in healthy people, as shown by a meta-analysis of 18 fMRI studies with 306 participants. The analysis used multilevel kernel density analysis and ensemble thresholding to minimize bias. These findings help map the functional neuroanatomical effects of ketamine, which may inform its therapeutic use for psychiatric and neurological conditions. Future research should examine both short- and long-term neural effects in clinical populations.