The investigators' aim was to conduct the first prospective, randomized, placebo-controlled, double-blind clinical trial of metyrapone as additive treatment in depression. Metyrapone was preferred, since this compound inhibits selectively the 11β-hydroxylase and the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), thereby exerting direct effects within the central nervous system (CNS). The additive approach was applied because the intended inclusion of severely depressed patients made a pure placebo group ethically challenging. Furthermore, the continuous use of an antidepressant allowed a standardized follow up after the double-blind period.