Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)

Some people with depression respond well to an antidepressant but others require a combination of two medications to get better. The current standard practice is to prescribe an antidepressant first, wait 8 weeks for response and then prescribe an additional medication to those who did not respond to the antidepressant. New findings show that we can predict who is likely to need combined treatment, based on patterns of depressive symptoms and brain activity. The OPTIMUM-D study will test whether giving combined medication at the start of treatment, rather than waiting 8 weeks, improves depression treatment outcomes overall, or specifically for individuals who are predicted to not respond to an antidepressant alone. OPTIMUM-D will enroll 704 adults with depression across 8 Canadian sites. The participants will be randomly divided into two equal groups. Participants in the first group will be given treatment with an antidepressant alone. Participants in the second group will be given a combined treatment including an antidepressant and an add-on medication that enhances the antidepressant effect. We will also measure symptoms and brain activity that predicted response and non-response to antidepressants in previous trials. After 8 weeks of treatment, we will measure outcomes. At the end of the study, we will answer two questions: Does combined treatment lead to better outcomes than antidepressant alone? Do people with a symptom and brain activity profile predictive of antidepressant non-response benefit more from combined treatment? If the answer to either question is positive, it will change how depression is treated in practice.