Grant: Operating Grant

At least 50% of older adults with depression fail to improve with first-line antidepressant treatment and there are limited clinical trial data to guide management of patients who develop treatment resistance. Our centre is involved in a large academic clinical trial. All patients coming to this study receive a 3 month course of an antidepressant. This study creates an opportunity to advance our understanding of the biological mechanisms underlying treatment-resistance and how to predict treatment response in late-life depression (LLD). Cortical inhibition (CI) is an important brain function that shows a specific pattern of disturbance in younger patients with treatment-resistant depression. As the aging process leads to a decrease in CI, this may be of particular importance in treatment-resistant late-life depression. Yet, this has not been studied. Using a non-invasive neurophysiological technique called transcranial magnetic stimulation (TMS), CI can be measured in a reliable and accurate manner. Therefore, the proposed study will take advantage of the clinical trial platform to evaluate CI in a sample of older depressed adults. We aim to determine if CI deficits at baseline predict treatment resistance to venlafaxine XR. In addition, we will compare CI in depressed older adults to a group of age- and sex- matched, non-depressed older adults. Insights generated by this research will add to the understanding of treatment resistance in LLD in several important ways. First, these findings will help to clarify the biological mechanisms of depression in older adults. Second, these findings may serve to provide early identification of patients who will not respond to medications, ultimately leading to more personalized treatment decisions.