Treatment of Atypical Depression: Phenelzine, Imipramine, and Placebo

The concept of atypical depression dates back to the late 1950s, when British investigators at St. Thomas’s Hospital in London attempted to characterize patients responding to the newly available antidepressant drug iproniazid. In an open clinical series, iproniazid, the first available monoamine oxidase inhibitor (MAOI), helped depressed patients who manifested prominent anxiety, hysterical features, phobic anxiety, emotional over-reactivity, assorted psychophysiological symptoms, fatigue, initial insomnia, reverse diurnal variation, poor ECT response, and adequate premorbid personality (West and Dally 1959). These patients appeared distinct from the endogenous and melancholic depressives, who were highly ECT responsive. Sargant (1961) also noted precipitating stress, irritability, tendency to blame others, weight loss, and difficulty in coping as features of this atypical depressive group.