Metyrapone as augmentation strategy in the treatment of major depression

Inhibitors of steroid-synthesis have been reported to exert antidepressive effects. The hypothesis was tested whether addition of metyrapone to standard antidepressants induces a more rapid, more efficacious and sustained treatment response in patients with Major Depression. 63 in-patients with a DSM-IV diagnosis of Major Depression and a baseline score ≥ 18 points on the Hamilton Rating Scale for Depression in a Double-blind, randomized, placebo controlled trial. Random allocation to two treatment groups receiving either placebo or metyrapone (1g/die) for the first 3 weeks during a 5 week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine). Primary outcome criteria were number of responders and time to onset-of-action. Using intent-to-treat analysis, a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared to placebo (day 21: 13 of 30 patients; Fisher’s exact p=0.031; day 35: 10 of 30 patients; Fisher’s exact p=0.047). The clinical course of patients treated with metyrapone showed an earlier onset-of-action (Kaplan-Meier analysis; log-rank test p<0.006) beginning in the first week. Metyrapone is an effective adjunct in the treatment of major depression accelerating the onset of antidepressant action.