This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wolkowitz, O. M. Articles by Reus, V. I. Search for Related Content PubMed PubMed Citation Articles by Wolkowitz, O. M. Articles by Reus, V. I. Related Collections Endocrinology Pharmacology Depression Reviews

Treatment of Depression With Antiglucocorticoid Drugs

From the Department of Psychiatry (O.M.W., V.I.R.), University of California, San Francisco, School of Medicine, San Francisco, CA.

Address reprint requests to: Owen M. Wolkowitz, MD, Department of Psychiatry, University of California, San Francisco, School of Medicine, 401 Parnassus Ave., San Francisco, CA 94143-0984. Email: owenw{at}itsa.ucsf.edu

OBJECTIVE: The theoretical and empirical rationales for the potential therapeutic use of antiglucocorticoid agents in the treatment of depression are reviewed.

METHOD: Individual case reports, case series, open-label, and double-blind, controlled trials of the usage of cortisol-lowering treatments in Cushing’s syndrome and major depression are evaluated and critiqued.

RESULTS: In each of the 28 reports of antiglucocorticoid treatment of Cushing’s syndrome, antidepressant effects were noted in some patients; the largest two series document a response rate of 70% to 73%. Full response, however, was at times erratic and delayed. Across the 11 studies of antiglucocorticoid treatment of major depression, some degree of antidepressant response was noted in 67% to 77% of patients. Antidepressant or antiobsessional effects of antiglucocorticoid augmentation of other psychotropic medications have also been noted in small studies of patients with treatment-resistant depression, obsessive-compulsive disorder, and schizoaffective disorder or schizophrenia.

CONCLUSIONS: These promising results with antiglucocorticoid treatment must be interpreted cautiously because of the small sample sizes and heterogeneity of the studies reviewed, the bias favoring publication of positive results, and the open-label nature of most of the studies. Although definitive controlled trials remain to be conducted, there is a consistent body of evidence indicating that cortisol-lowering treatments may be of clinical benefit in select individuals with major depression and other hypercortisolemic conditions.

Key Words: antiglucocorticoid • depression • cortisol • Cushing’s syndrome • Cushing’s disease • antidepressant

Abbreviations: ACTH = adrenocorticotropic hormone; CRH =corticotropin-releasing hormone; DST = dexamethasone suppressiontest; HDRS = Hamilton Depression Rating Scale; LHPA =limbic-hypothalamic-pituitary-adrenal; PRL = prolactin; UFC =urinary free cortisol; 5HT = serotonin.

This article has been cited by other articles:

				E. A. Lawson, D. Donoho, K. K. Miller, M. Misra, E. Meenaghan, J. Lydecker, T. Wexler, D. B. Herzog, and A. Klibanski Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa J. Clin. Endocrinol. Metab., December 1, 2009; 94(12): 4710 - 4716. [Abstract] [Full Text] [PDF]

				F. M. Horne and D. L. Blithe Progesterone receptor modulators and the endometrium: changes and consequences Hum. Reprod. Update, November 1, 2007; 13(6): 567 - 580. [Abstract] [Full Text] [PDF]

				X.-M. Ou, K. Chen, and J. C. Shih Glucocorticoid and Androgen Activation of Monoamine Oxidase A Is Regulated Differently by R1 and Sp1 J. Biol. Chem., July 28, 2006; 281(30): 21512 - 21525. [Abstract] [Full Text] [PDF]

				A. Kier, J. Han, and L. Jacobson Chronic Treatment with the Monoamine Oxidase Inhibitor Phenelzine Increases Hypothalamic-Pituitary-Adrenocortical Activity in Male C57BL/6 Mice: Relevance to Atypical Depression Endocrinology, March 1, 2005; 146(3): 1338 - 1347. [Abstract] [Full Text] [PDF]

				H. Jahn, M. Schick, F. Kiefer, M. Kellner, A. Yassouridis, and K. Wiedemann Metyrapone as Additive Treatment in Major Depression: A Double-blind and Placebo-Controlled Trial Arch Gen Psychiatry, December 1, 2004; 61(12): 1235 - 1244. [Abstract] [Full Text] [PDF]

				L. R. Rappa, M. Larose-Pierre, E. Branch III, A. J. Iglesias, D. A. Norwood, and W. A. Simon Desperately Seeking Serendipity: The Past, Present, and Future of Antidepressant Therapy Journal of Pharmacy Practice, December 1, 2001; 14(6): 560 - 569. [Abstract] [PDF]

				R. McQUADE and A. H. Y. YOUNG Future therapeutic targets in mood disorders: the glucocorticoid receptor The British Journal of Psychiatry, November 1, 2000; 177(5): 390 - 395. [Abstract] [Full Text] [PDF]

				Y. Dwivedi, H. S. Rizavi, J. S. Rao, and G. N. Pandey Modifications in the Phosphoinositide Signaling Pathway by Adrenal Glucocorticoids in Rat Brain: Focus on Phosphoinositide-Specific Phospholipase C and Inositol 1,4,5-Trisphosphate J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 244 - 254. [Abstract] [Full Text]

				Y. Dwivedi and G. N. Pandey Adrenal Glucocorticoids Modulate [3H]Cyclic AMP Binding to Protein Kinase A (PKA), Cyclic AMP-Dependent PKA Activity, and Protein Levels of Selective Regulatory and Catalytic Subunit Isoforms of PKA in Rat Brain J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 103 - 116. [Abstract] [Full Text]

				P. C. Trask, P. Esper, M. Riba, and B. Redman Psychiatric Side Effects of Interferon Therapy: Prevalence, Proposed Mechanisms, and Future Directions J. Clin. Oncol., June 11, 2000; 18(11): 2316 - 2326. [Abstract] [Full Text] [PDF]

				O. G. Cameron Psychopharmacology Psychosom Med, September 1, 1999; 61(5): 585 - 590. [Full Text] [PDF]