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May 25, 2019

Approximately 2/3 of patients with major depressive disorder (MDD) do not achieve remission despite adequate treatment with an antidepressant. It would be of utmost benefit to clinicians to be able to predict which patients would do better with which specific next-step treatment strategies -whether it be switching to a different antidepressant, combination of two antidepressants, or augmentation with a psychotropic from another drug class -rather than relying on trial and error. In this US Department of Veterans Affairs study (the VA Augmentation and Switching Treatments for Improving Depression Outcomes; VASTD), the authors sought to investigate which demographic and clinical features may help predict remission from depression and also determine which next-step treatment may be right for the individual patient. In this particular trial, patients with MDD who were non-responsive to an antidepressant were either switched from their current antidepressant to bupropion (switching strategy), had bupropion added to their current antidepressant treatment (combination strategy), or had their current antidepressant augmented with aripiprazole (augmentation strategy). The data showed that several factors predicted non-remission even after any of these next-step strategies: unemployment, health-related quality of life, severity of depression, anxiety, chronicity of depression, shorter duration of index medication treatment, childhood adversity, complicated grief, impaired baseline quality of life and functioning, and lack of positive mental health. Interestingly, 2 factors were found to predict optimal next-step strategies: age and presence of mixed features (hypomania during major depressive episode) (Figure). It was found that individuals with non-remitting MDD may do best with the next-step strategy of augmentation with aripiprazole compared to switching to bupropion and individuals with mixed features have a higher chance of remission if either augmented with aripiprazole or combination with bupropion. These data are especially meaningful given that the treatment guidelines for treating depression with mixed features support the use of select second generation antipsychotics (including aripiprazole). There are many switching, combination, and augmentation strategies involving psychotropics other than bupropion and aripiprazole; however, these data offer a useful, albeit somewhat limited, set of evidence for what the next-step treatments may be in select patients.