Original ContributionsEffects of Testosterone Replacement in Middle-Aged Men With Dysthymia A Randomized, Placebo-Controlled Clinical TrialSeidman, Stuart N. MD*†; Orr, Guy MD‡; Raviv, Gil MD§∥; Levi, Rachel BA‡; Roose, Steven P. MD*†; Kravitz, Efrat BSc‡∥; Amiaz, Revital MD‡∥; Weiser, Mark MD‡∥ Author Information From the *Department of Psychiatry, College of Physicians and Surgeons of Columbia University; †New York State Psychiatric Institute, New York, NY; Departments of ‡Psychiatry and §Urology, Chaim Sheba Medical Center, Tel Hashomer; and ∥Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Received November 24, 2008; accepted after revision March 2, 2009. Reprints: Stuart N. Seidman, MD, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr Unit 98, New York, NY 10032 (e-mail: [email protected]). This research was funded by grants to S.N.S. from the National Institute of Mental Health (MH01740) and from the National Alliance for Research on Schizophrenia and Depression (Young Investigator Award). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML andPDF versions of this article on the Journal's Website (www.psychopharmacology.com). Journal of Clinical Psychopharmacology: June 2009 - Volume 29 - Issue 3 - p 216-221 doi: 10.1097/JCP.0b013e3181a39137 Buy SDC Metrics Abstract Mid-life onset male dysthymic disorder (DD) seems to be a distinct clinical condition with limited therapeutic options. Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy, though this strategy has received limited systematic study. We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone (T) level (i.e, screening total serum testosterone <350 ng/dL). Enrolled men were randomized to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days. The primary outcome measures were the Clinical Global Impression (CGI) improvement score and the 21-item Hamilton Depression Rating Scale (HDRS) score. Twenty-three patients were randomized. The mean (SD) age of the enrolled patients was 50.6 (7.0) years and that of total testosterone level was 339 (93) ng/dL. The median duration of the current dysthymic episode was 3.6 (2.3) years, and the mean (SD) HDRS was 14.0 (2.9). After the intervention, the mean HDRS score decreased significantly more in the testosterone group (7.46 [4.56]) than in the placebo group (1.8 [4.13], t21 = −3.07, P = 0.006). Remission, defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8, was achieved by 7 (53.8%) of 13 in the testosterone group and 1 (10%) of 10 in the placebo group (P = 0.03). Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia. © 2009 Lippincott Williams & Wilkins, Inc.