Treatment-resistant depression is a heterogeneous condition that occurs within a psychosocial milieu. The impact of prior pharmacologic interventions may have been adversely affected by a poor therapeutic alliance, low social support, life stress, or chronic adversity and cognitive or personality factors such as neuroticism or pessimism. This article considers the psychosocial factors that predispose to treatment-resistant depression and the psychotherapeutic principles thought to be helpful in both shorter- and longer-term treatment plans. We focus on the interpersonal, cognitive, and behavioral forms of treatment that constitute the depression-focused psychotherapies, which have been studied in major depressive disorder. Also discussed are modifications in treatment planning necessary to take into account the complexity of treatment-resistant depression.
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