Abstract

BACKGROUND:

Treatment-resistant depression is a persistent clinical problem. Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement, although this strategy has received limited systematic study.

OBJECTIVE:

The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression.

METHOD:

Twenty-six healthy adult men with major depressive disorder, partial or nonresponse to 2 adequate antidepressant trials during the current episode, and currently using a selective serotonin reuptake inhibitor were randomized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo, in addition to their existing selective serotonin reuptake inhibitor regimen, for 6 weeks. The main outcome measure was the Hamilton Rating Scale for Depression score.

RESULTS:

The mean age was 46.4 +/- 10.8 years; mean total testosterone level, 417.5 +/- 197 ng/dL; mean baseline Hamilton Rating Scale for Depression score, 22.2 +/- 5.2; and median duration of the current depressive episode, 6.3 +/- 10.6 years. Hamilton Rating Scale for Depression scores decreased significantly in both testosterone (8.4) and placebo (7.4) groups. Antidepressant response, defined as a 50% decline in Hamilton Rating Scale for Depression score, was achieved by 53.8% (7/13) in the testosterone group and 23.1% (3/13) in the placebo group (P = 0.226).

CONCLUSION:

Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression.