Ketamine for Depression Relapse Prevention Following ECT

Depression affects up to 20% of people in their lifetime and can be a severe debilitating illness. Indeed, the World Health Organisation has estimated that depression will soon be the second leading contributor to the burden of disease worldwide. One of the big problems for patients and doctors is that currently available antidepressant drugs and psychotherapies do not work for 30% of people. However, about 60% of such treatment-resistant patients will recover fully with electroconvulsive therapy (ECT). Even though it was developed over 75 years ago, ECT continues to be the most powerful treatment for severe, often life-threatening, depression. Despite that, we have recently reported that severe depression symptoms return (called a "relapse") in nearly 40% of such responders within six months of completing a course of ECT. Actually, such high relapse rates are seen for all patients with treatment-resistant depression, irrespective of what treatment they have received. There is thus an urgent need for better treatments to prevent relapse and one such possibility is an old drug called ketamine. Ketamine blocks the activity of glutamate, one of the major chemical messenger systems in the brain. Because of this effect it is sometimes used as an anaesthetic but it can also make you feel a bit "high" and so is sometimes abused as a recreational drug. Fortunately, in small doses it is quite safe. Recently, it has been found that ketamine has a remarkably rapid, but brief, antidepressant effect, including reducing suicidal thoughts. We wish to evaluate ketamine as a way to reduce relapse rates in people who have just been treated successfully with ECT for severe depression. Developing such a new treatment, and understanding how it works, would be of tremendous benefit to persons with severe depression, their families, and the wider society.