In this competitive continuation application, the primary goal is to evaluate the antidepressant effects of testosterone compared to fluoxetine in a double-blind randomized placebo controlled clinical trial for HIV-positive patients with major depression as well as clinical symptoms of hypogonadism. In the first 2 years of the ongoing testosterone grant, the investigators treated HIV-positive men with clinical symptoms of hypogonadism in a 12-week open trial followed by a 6-week double-blind placebo controlled discontinuation trial with improved libido as the major outcome criterion. In the discontinuation phase, 79 percent (26/33) randomized to testosterone maintained response, compared to 15 percent (5/34) for placebo. Twenty-seven men in this sample had major depression. Of these, 21 (78 percent) had significantly improved mood after 8 weeks of open treatment. In the ongoing NIMH-supported placebo controlled trial of fluoxetine, 36 patients with major depression have been treated with fluoxetine, and 22 with placebo in a double-blind randomized trial. Response rates to fluoxetine and placebo respectively have been 75 percent and 45 percent. The results, taken together, suggest the value of a study designed to directly compare antidepressant effects of testosterone, fluoxetine, and placebo. The design will be an 8-week double blind 3-arm study of testosterone injections (and placebo capsules), fluoxetine (and placebo injections), and placebo (placebo injections and placebo capsules). The investigators propose a 2:1:1 randomization with 140 patients (70:35:35) completing the 8-week trial. The testosterone arm is the largest since they seek to determine whether an antidepressant effect is secondary to or independent of androgenic (increased libido) or anabolic (increased weight and/or muscle mass) effects. After this trial, treatment will be continued for another 4 months to assess longer-term patient acceptance, side effects, and safety, using HIV RNA viral load to gauge immune effects. The intent is to identify a practical, inexpensive, useful treatment for community settings.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052037-06
Application #
2675193
Study Section
Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
Program Officer
Rausch, Dianne M
Project Start
1993-09-30
Project End
2001-04-30
Budget Start
1998-05-05
Budget End
1999-04-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Rabkin, Judith G; Wagner, Glenn J; McElhiney, Martin C et al. (2004) Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol 24:379-85
Daly, R C; Schmidt, P J; Roca, C A et al. (2001) Testosterone's effects not limited to mood. Arch Gen Psychiatry 58:403-4
Rabkin, J G; Wagner, G J; Rabkin, R (2000) A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry 57:141-7; discussion 155-6
Rabkin, J G; Wagner, G J; Rabkin, R (1999) Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism. J Clin Psychopharmacol 19:19-27
Maguen, S; Wagner, G J; Rabkin, J G (1998) Long-term testosterone therapy in HIV-positive men: side-effects and maintenance of clinical benefit. AIDS 12:327-8
Wagner, G; Rabkin, J; Rabkin, R (1998) Exercise as a mediator of psychological and nutritional effects of testosterone therapy in HIV+ men. Med Sci Sports Exerc 30:811-7
Wagner, G J; Rabkin, J G; Rabkin, R (1998) Testosterone as a treatment for fatigue in HIV+ men. Gen Hosp Psychiatry 20:209-13
Wagner, G J; Rabkin, J G (1998) Testosterone therapy for clinical symptoms of hypogonadism in eugonadal men with AIDS. Int J STD AIDS 9:41-4
Wagner, G J; Maguen, S; Rabkin, J G (1998) Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients. Psychiatr Serv 49:239-40
Wagner, G J; Rabkin, J G (1998) Testosterone, illness progression, and megestrol use in HIV-positive men. J Acquir Immune Defic Syndr Hum Retrovirol 17:179-80

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