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In two thirds of patients, depression fails to remit with the initial antidepressant. In those whose depression does not remit after a second medication trial, response to subsequent single or combination agents is low (see STAR*D). Controlled trials have shown improved response after augmentation of antidepressants with other antidepressants, lithium, or thyroid hormone. The benefit of using atypical antipsychotics, which can have problematic metabolic effects, for this off-label indication is less clear; several small trials have had positive results, but the two largest trials had negative results. This similarly large, manufacturer-sponsored trial tested the efficacy of the atypical antipsychotic, aripiprazole, which has few metabolic e…