This paper provides an overview of antidepressant nonresponse and the role of augmentation strategies in the management of treatment-resistant depression. When effective, the more widely used augmentation strategies, including lithium salts, thyroid hormones, pindolol, buspirone, and psychostimulants, share two important advantages when compared with "switching" strategies: avoidance of ill effects associated with discontinuing the initial antidepressant and rapidity of onset of action. Ideally, advances in the understanding of the neurobiology of mood disorders and mechanisms of antidepressant response will permit a more efficient and specific matching between patient, initial antidepressant, and subsequent strategy for enhancing response to treatment.
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