In an effort to improve the treatment of individuals with depression, the National Institutes of Mental Health and the Depression Trials Network are conducting the Combination Medication to Enhance Depression Outcomes (CO-MED) Trial. The overall aim of CO-MED is to enhance remission rates for representative, self-declared outpatients with chronic or recurrent nonpsychotic major depressive disorder, treated in primary or psychiatric care settings.

Current evidence indicates that remission, the goal of treatment, is found in only about one-third of representative depressed outpatients treated for up to 14 weeks with an initial SSRI. In addition, even for those who do respond or remit, over one-third relapse in the subsequent 12 months. Combinations of antidepressants are used in practice at the second or subsequent steps when relapse occurs in the continuation phase, or, in some cases, even acutely as a first step when speed of effect is a clinical priority. Pilot studies of combinations suggest acceptable tolerability and higher remission rates than expected. Such combinations could potentially offer higher remission rates, lower attrition, or greater longer-term benefit if used as initial treatments as compared to monotherapy.

CO-MED provide a proof of the concept that two different antidepressant medication combinations used in the first treatment step in a depressive episode will enhance remission rates, be tolerable, and result in acceptable attrition and provide better sustained benefits in the longer term than a single antidepressant medication. If positive, results would likely recommend major revisions in how patients with chronic or recurrent major depressive disorder are treated in practice.


This CO-MED web site was created for and describes the activities of an NIMH-funded collaborative study on the treatment of depression.

If you are seeking immediate help for treatment of depression, we recommend that you contact your clinician or your nearest emergency room. This web site is not intended to provide help or advice to individuals about depression. If you need information about depression, visit the NIMH web site page about depression.