title: Modulation of the mineralocorticoid receptor as add-on treatment in depression: a randomized, double-blind, placebo-controlled proof-of-concept study.
abstract: 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 (Hamilton Depression Scale-17 score>18) in a double-blind, randomized, placebo-controlled trial. Patients were randomized in a 2:2:1 fashion to fludrocortisone (0.2 mg/d, n=24) or spironolactone (100 mg/d, n=27) or placebo (n=13) for the first 3 weeks during a 5-week treatment with escitalopram. No differences in mean HAMD change scores and in time to response emerged between treatments. However, among the responders, patients treated with fludrocortisone responded faster (Breslow test, 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 (F=3.78, p=0.03). In the whole group, plasma cortisol increased during spironolactone and decreased during fludrocortisone treatment (F=2.4, p=0.04). In patients treated with fludrocortisone, non-responders had elevated cortisol values compared to responders throughout the study period (F=5.1, p=0.04). Stimulation of MR with fludrocortisone as adjunct to escitalopram accelerated the response in the group of responders while no effect emerged in the sample as a whole. A larger randomized controlled trial is warranted.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Germany. otte@uke.uni-hamburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
authors.forename: Kim
authors.initials: K
authors.lastname: Hinkelmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Moritz
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.forename: Holger
authors.initials: H
authors.lastname: Jahn
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D010045:Outpatients; D018161:Receptors, Mineralocorticoid / Q000819:agonists*; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D015283:Citalopram; D013148:Spironolactone; D005438:Fludrocortisone; D006854:Hydrocortisone