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 benefitfrom treatment with standard, first-line antidepressant agents. In this paper, alternate antidepressantstrategies are reviewed within the context of a five-stage strategy, ranging from lesser to greater degreesof treatment resistance. The overall strategy recommended progresses from simpler (i.e., an alternatemonotherapy) to more complex strategies (i.e., combination or augmentation regimens), withthe nonselective monoamine oxidase inhibitors (+/- lithium salts) and electroconvulsive therapy typicallyreserved for treatment of Stages III and IV of resistance, respectively. Psychotherapeutic managementalso is an important ingredient in the ongoing treatment of these patients, particularly tocounteract the demoralization and frustration that understandably accompany the failure to respondto so many treatments.