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Testosterone and Depression

Systematic Review and Meta-Analysis

Zarrouf, Fahd Aziz, MD*; Artz, Steven, MD; Griffith, James, MD; Sirbu, Cristian, MD, PhD; Kommor, Martin, MD

Journal of Psychiatric Practice®: July 2009 - Volume 15 - Issue 4 - p 289-305
doi: 10.1097/01.pra.0000358315.88931.fc

Background. Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients.

Objective. The objective of this study was to explore the effect of TT administration on depression using both a systematic review of the literature and a meta-analysis.

Methodology. A search was conducted of MEDLINE, the Clinical Trials Registry, and Cochrane Central for English-language publications concerning randomized, placebo-controlled trials involving use of TT therapy in depressed patients. We searched for additional trials in the individual reference lists of the articles identified in the search. A study was judged to be relevant for inclusion in this review and meta-analysis if it reported original data from a controlled trial comparing use of TT and placebo in patients diagnosed with a depressive disorder according to DSM criteria, and the treatment response was evaluated according to changes on the Hamilton Rating Scale for Depression (HAM-D). We extracted the following data from the identified studies: study source, total number of participants in the study and in each treatment group, participants' ages, number of participants with a diagnosis of hypogonadism or HIV/AIDS, study duration, type of intervention, and change in HAM-D scores in the groups receiving TT versus placebo. The meta-analysis evaluated the effect of TT replacement on response in depressed patients as measured by change in HAM-D scores in the available placebo-controlled, randomized clinical trails.

Results. Seven studies (N=364) were identified that included a placebo-control group in a double-blind design. Eligibility criteria were clearly reported in all trials. Meta-analysis of the data from these seven studies showed a significant positive effect of TT therapy on HAM-D response in depressed patients when compared with placebo (z=4.04, P<0.0001). Subgroup analysis also showed a significant response in the subpopulations with hypogonadism (z=3.84, P=0.0001) and HIV/AIDS (z=3.33, P=0.0009) as well as in patients treated with TT gel (z=2.32, P=0.02).

Conclusions. TT may have an antidepressant effect in depressed patients, especially those with hypogonadism or HIV/AIDS and elderly subpopulations. The route by which TT is administered may play a role in treatment response.

*West Virginia University School of Medicine Charleston Division; currently: Cleveland Clinic-Neurological Institute, Cleveland, OH

West Virginia University School of Medicine Charleston Division

West Virginia University School of Medicine Charleston Division and Charleston Area Medical Center Health Education and Research Institute.

Funding/Support: This project was supported by the Charleston Area Medical Center (CAMC) Health Education and Research Institute, Inc. and the CAMC Foundation, Inc. of Charleston, West Virginia. The funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Please send correspondence and reprint requests to: Fahd Aziz Zarrouf, MD, Cleveland Clinic- Neurological Institute, 9500 Euclid Avenue/FA20, Cleveland OH 44195

We thank Shirley Hicks (West Virginia University); and Dania Zahlouk (University of Charleston) for their assistance. Data from this study were previously presented as a poster at the Annual Meeting of American Psychosomatic Society, in March 2008.

Disclosure: Dr Artz is on the speaker's bureau for Solvay Pharmaceuticals Inc.

Copyright © 2009 Wolters Kluwer Health, Inc. All rights reserved.