An 8-Week Open-Label Trial of a 6-Day Course of Mifepristone for the Treatment of Psychotic Depression

George M. Simpson, M.D.; Adel El Sheshai, M.D.; Nasser Loza, M.D.; Steven J. Kingsbury, M.D., Ph.D.; Mohamed Fayek, M.D.; Ahmed Rady, M.D.; and Waleed Fawzy, M.D.

Objective: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications.

Method: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003.

Results: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance.

Conclusion: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study.

(J Clin Psychiatry 2005;66:598-602)

Received May 18, 2004; accepted Nov. 8, 2004. From the Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles (Drs. Simpson, Kingsbury, and Fayek); the Department of Psychiatry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt (Drs. El Sheshai and Rady); and Behman Psychiatric Hospital, University of Cairo, Cairo, Egypt (Drs. Loza and Fawzy).

Dr. Simpson serves as a consultant to Pfizer and Janssen and has received grant support from Pfizer, Janssen, and AstraZeneca. Dr. El Sheshai serves as a consultant to Pfizer and Janssen. Dr. Fayek has received grant/research support from Pfizer, AstraZeneca, and SmithKline and has served on the speakers or advisory boards for Pfizer, Eli Lilly, and Bristol-Myers. All other authors report no financial affiliation or other relationship relevant to the subject matter of this article.

Corresponding author and reprints: George M. Simpson, M.D., Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, 2020 Zonal Avenue, IRD 202, Los Angeles, CA 90033 (e-mail: gsimpson@usc.edu).