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.
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.
European Psychiatry
March 1, 2023
J. H. Shepherd, C.t.m. Baten, A. C. Klassen et al.
Serotonergic psychedelics such as LSD, psilocybin, and MDMA significantly alter neural activation in several regions of the cerebral cortex and basal ganglia. Some effects are common across these drugs, while others are unique to each substance. This meta-analysis combined functional MRI studies of both clinical and healthy participants, using multilevel kernel density analysis with ensemble thresholding. The findings clarify the functional neuroanatomy associated with these drugs and may guide future research into their therapeutic and adverse effects, particularly for emerging psychiatric treatments.