When at first you don't succeed: sequential strategies for antidepressant nonresponders

Now, more than ever before, a wealth of options exists for depressed patients who do not benefit from treatment with standard, first-line antidepressant agents. In this paper, alternate antidepressant strategies are reviewed within the context of a five-stage strategy, ranging from lesser to greater degrees of treatment resistance. The overall strategy recommended progresses from simpler (i.e., an alternate monotherapy) to more complex strategies (i.e., combination or augmentation regimens), with the nonselective monoamine oxidase inhibitors (+/- lithium salts) and electroconvulsive therapy typically reserved for treatment of Stages III and IV of resistance, respectively. Psychotherapeutic management also is an important ingredient in the ongoing treatment of these patients, particularly to counteract the demoralization and frustration that understandably accompany the failure to respond to so many treatments.