Ketamine as an Augmentation Strategy for Electroconvulsive Therapy (ECT) in Depression

The study aims to compare outcomes of Electroconvulsive Therapy (ECT) using ketamine versus methohexital anesthesia in depressed patients. The investigators hypothesize that patients who receive ketamine anesthesia during ECT will achieve remission status faster than those receiving methohexital anesthesia. Also, at the end of the ECT course subjects will display fewer cognitive side effects compared to those treated with methohexital anesthesia.

Despite major advances in the treatment of mood disorders, depression remains a serious public health problem. Delayed onset of response and lack of efficacy in a significant portion of patients are the limitations of pharmacotherapy. Electroconvulsive therapy (ECT) has been shown to provide fast amelioration of depressive symptoms and its efficacy is reported to be 65 to 85%. However, one of the main limiting factors for its use is the cognitive impairment, which is directly related to the number of ECT sessions. There is increased evidence for the mediation of glutamate in the pathophysiology of depression, as suggested by the potential antidepressant effect of drugs that modulate glutamate transmission. Open studies and recent case reports demonstrate a rapid antidepressant effect of intravenous ketamine - a non-competitive antagonist at the glutamate N-methyl-D-aspartate (NMDA) receptor. Ketamine is a general anesthetic used commonly for procedural sedation. Ketamine has no anticonvulsant properties. It is used as an alternative to methohexital - a barbiturate with anticonvulsant properties - in patients with high seizure threshold. A recent open non-randomized trial by Okamoto shows a faster response when ECT is given with ketamine anesthesia. In a recent review Gregory-Roberts et al suggest that available evidence in animals and humans supports the prediction that ketamine could effectively prevent ECT -induced persistent retrograde amnesia and improve or hasten therapeutic response. We propose a double-blind randomized controlled pilot study to measure both therapeutic efficacy and cognitive side effects of ECT using ketamine compared to methohexital - the gold standard anesthetic in ECT - in depressed patients. Thirty patients who are scheduled to receive an acute course of ECT for major depressive episode. Inpatients and outpatients will be screened by the ECT psychiatrists who participate in this study. Patients who are able and willing to provide written informed consent will be randomly assigned on a 1:1 ratio to receive either a course of bifrontal ECT using ketamine 1-2 mg/kg or methohexital anesthesia0.5-1.0 mg/kg. Subjects will receive a standard acute course of ECT (3X/week. Raters and subjects will be masked to group assignment. Parallel with these procedures we will also collect magnetic resonance imaging (MRI) data on these subjects. The timeline of neuroimaging and it relation to ECT is a baseline MRI prior to first ECT, and then a follow up MRI after the first ECT (\< 36hrs after), and a final MRI after 9 ECTs or if patient remits. All subjects will receive structural (i.e. diffusion tensor imaging and spectroscopy) and functional MRI exams. In addition to the imaging procedures detailed above, we also plan to acquire imaging data on healthy individuals with similar timeline. Healthy volunteers will be scanned three times; the first and second scans will be 24-48 hours apart, while the second and third scans will be two weeks apart. The imaging sessions will follow the same protocol as in the patients. The collection of control data is necessary in order to demonstrate that imaging findings are not due to acclimatization to scanner environment or other confounding sources. Compensation for participating in the MRI component is $75 per MRI.