Project 458887

Major depressive disorder (MDD) is the second leading cause of disability worldwide. Although there are effective treatments for depression, many patients do not achieve remission, and any significant response usually occurs after a few weeks. To date, the most effective approach for rapid intervention in treatment-resistant depression has been electroconvulsive therapy (ECT) although it holds many downsides such as hospitalization, limited access, and potential memory loss. A new intervention for the treatment of depression is intravenous ketamine. The antidepressant effects of ketamine often occur within a few hours, and peak within 24 hours in treatment-resistant patients. This response that can be obtained within one day with ketamine is comparable to that obtained with standard medications for depression after 8 weeks. While both ECT and ketamine have rapid acting antidepressant effects, the mechanisms underlying their effects remain unknown. The goal of this study is to use fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging to directly compare the underlying mechanisms of each of these treatment strategies as well as those associated with predicting clinical response. We will enroll 30 male and female patients with MDD or bipolar disorder. They will be randomly assigned to either ECT or ketamine. Prior to treatment, participants will undergo an FDG-PET scan to detect changes in glucose metabolism in the brain. Specifically, the FDG-PET scan will help visualize brain activity by measuring glucose uptake, where more active brain regions indicate increased glucose uptake. Participants will receive between 9 to 12 treatments administered three times a week over 3 or 4 weeks. After treatment, participants will undergo a second FDG-PET scan allowing us to identify and compare glucose activity changes with treatment. Ultimately, this study may improve our ability to tailor treatment for patients experiencing treatment-resistant mood disorders.