Systematic review · 2025
Review of brain-imaging studies on ketamine, reward circuits and depression
- Original title
- Effects of glutamatergic modulators on striatal activation, functional connectivity and reward in persons with major depressive disorder and healthy controls: A systematic review of fMRI studies.
- Authors
- Teopiz KM, Wong S, Le GH, et al.
- Journal
- Journal of affective disorders, 2025
- Molecules
- Ketamine, Other
- Conditions
- Depression, Treatment-resistant depression, Healthy volunteers
- Evidence grade
- Low
- Source
- Read the original paper
The question
Do drugs that act on the brain’s glutamate system, such as ketamine, change activity and connections in the brain circuits linked to reward and pleasure in people with major depression?
What they did
The authors searched four research databases (PubMed, OVID, Scopus, Web of Science), plus reference lists and Google Scholar, from the earliest records up to 22 July 2025. They looked for studies that used functional MRI, a scan that tracks blood flow as a marker of brain activity, to measure changes in the frontostriatal system (a set of connections between the frontal lobes and deeper reward-related regions) after people were given a glutamate-acting drug with possible antidepressant effects. Participants were either people with major depressive disorder or healthy volunteers.
What they found
Eleven fMRI studies met the criteria. Nine tested ketamine, one tested nitrous oxide and one tested memantine. The authors describe the evidence as preliminary: intravenous ketamine may alter functional connectivity in striatal brain regions in ways that could relate to improved reward processing in people with treatment-resistant depression. No pooled effect sizes or combined participant numbers were reported in the abstract.
The fine print
Only 11 studies were found, and most looked at one drug, so conclusions rest on a thin and uneven evidence base. The abstract does not report how many people were included, study designs, doses, or whether results were consistent across studies, and no statistical pooling was done. Brain-scan changes are surrogate markers, not proof of symptom improvement. This summary is based on the abstract alone.
What it means
Early brain-imaging work hints that ketamine may shift activity in reward-related brain circuits in depression, but the evidence is too limited and too varied to draw firm conclusions.
Evidence grade: Low. A narrative systematic review of only 11 small brain-imaging studies, with no pooled statistical analysis and no participant totals reported.
This summary is based on the study’s published abstract.