Treating depression with atypical features.

Depression with atypical features was first recognized in a subset of patients with depression who preferentially responded to the monoamine oxidase inhibitor (MAOI) phenelzine, in contrast to patients with melancholic depression. This article reviews the history of approaches in treating depression with atypical features. Initial studies in the early 1980s focused on phenelzine, but an unfavorable adverse effect profile limits its clinical use. Despite such difficulties, phenelzine remains the gold standard in eliciting high response rates in nearly two thirds of patients with atypical depression. Searches for agents with improved safety profiles led to studies of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), chromium, and cognitive therapy approaches. Of these, TCAs showed inferior efficacy to MAOIs but also had cumbersome adverse effects. SSRIs have reported efficacy, but a lack of direct comparative studies limits clinical decision making. Cognitive strategies have shown promise, but demonstrating efficacy in comparison with an MAOI and placebo is limited to a single study. Despite advances in agents for melancholic depression, treatment for atypical depression remains dependent upon older agents for the greatest efficacy.