Effect of ketamine on task-based functional magnetic resonance imaging findings in major depressive disorder: A mini-review

Background: Over the last two decades, ketamine has gained significant interest in psychiatry as a potential treatment for major depressive disorder (MDD), especially in individuals who are resistant to traditional therapies or are at a high risk of suicide. Task-based functional magnetic resonance imaging (fMRI) studies can provide insight into how ketamine alters brain function and contributes to its antidepressant properties. Methods: This mini-review followed the MOOSE guidelines for systematic reviews of observational studies. We conducted a literature search in PubMed, Web of Science, and Scopus aiming at identifying fMRI studies investigating the effect of ketamine on brain function in MDD. Results: Eight articles were included in the study. Results showed that ketamine affects brain activity in MDD, especially in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, and amygdala. Interestingly, the majority of the reviewed studies showed a correlation between the changes in brain activity induced by ketamine and improvements in clinical depressive symptoms. These correlations involved the prefrontal cortex, ACC, and cortico-cerebellar circuits. Limitations: Lack of longitudinal data on the lasting effects of ketamine on brain activity and the small number of studies. Conclusions: This review identifies key research areas that can enhance our understanding of ketamine's effects on the brain in MDD. It calls for studies on ketamine's mechanisms of action, long-term impact, dose-response optimization, and comparisons with other fast-acting antidepressants. Addressing these areas can optimize ketamine's therapeutic use and reveal new treatment targets.