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DOI: 10.1055/s-0029-1240192
Modulation of the mineralocorticoid receptor as add-on treatment in depression: a randomized, double-blind, placebo-controlled proof-of-concept study
Preclinical and clinical studies have suggested a role of the mineralocorticoid receptor (MR) in the response to antidepressants. We tested in a proof-of-concept study whether adding fludrocortisone (an MR agonist) or spironolactone (an MR antagonist) accelerates onset of action and improves efficacy of escitalopram in patients with major depression. We included 64 in- and outpatients with major depression in a double-blind, randomized, placebo-controlled trial. Patients were randomized in a 2:2:1 fashion to fludrocortisone (0.2mg/d, n=24) or spironolactone (100mg/d, n=27) or placebo (n=13) for the first 3 weeks during a 5-week treatment with escitalopram. More patients treated with fludrocortisone responded at day 7 compared with spironolactone or placebo (p=0.08). Further, among the responders, patients treated with fludrocortisone responded faster (p=0.05). The mean number of days to response was 16.0±2.6 days vs. placebo 22.2±2.0 vs. spironolactone 22.6±2.3 (p=0.03). Plasma cortisol increased during spironolactone and decreased during fludrocortisone treatment (p=0.04). In patients treated with fludrocortisone, non-responders had elevated cortisol values compared to responders throughout the study period (p=0.04). Stimulation of MR with fludrocortisone as adjunct to escitalopram accelerated the response, especially in the group of responders. A larger randomized controlled trial is warranted.