Abstract
Despite the introduction of a wide range of antidepressant drugs since the late 1950s, approximately 30–50% of depressed subjects do not respond to these agents. Various treatment strategies, both pharmacological and non-pharmacological, have been proposed for treatment-resistant depression. This paper critically reviews the studies of single and combined pharmacological treatments for tricyclic-resistant patients, with a particular discussion of lithium augmentation. The major inadequacies of these studies have been the frequent lack of definitions of treatment resistance, the heterogeneity of the depressed samples, and the infrequent use of double-blind, placebo-controlled designs. Two central issues, definition of treatment resistance and clinical predictors of response to pharmacological treatments, are discussed in detail. Finally, a suggested guideline for the management of tricyclic-resistant depression is proposed.