Twenty-three men and 23 women (aged 45-65 years) with midlife-onset major or minor depression who were not receiving antidepressant medications were randomly assigned to receive, in double-blind fashion, DHEA or placebo for 6 weeks. After a washout period of 1-2 weeks, each person received the alternate treatment for an additional 6 weeks. The dose of DHEA was 30 mg 3 times a day for 3 weeks, followed by 150 mg 3 times a day for 3 weeks. The mean score on the 17-Item Hamilton Depression Rating Scale (lower scores indicate less depression) was 13.5 at baseline, 7.5 after DHEA treatment, and 11.5 after placebo (p < 0.01 for the comparison of DHEA with both baseline and placebo). Similar results were seen using the Center for Epidemiologic Studies Depression Scale ratings. DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo. Thirteen patients who responded to DHEA elected to continue with an open-label trial of over-the-counter DHEA at a dose of 25-50 mg/day for 6-12 months. Of these 13 patients, 10 remained free of depression. No adverse effects were seen, with the exception of 1 woman who experienced a moderate increase in oily skin.

Comment: These results indicate that DHEA is an effective treatment for some patients with midlife-onset major or minor depression. The doses used in this study were extremely large relative to the presumed physiological requirement of approximately 5-15 mg/day for women and 10-30 mg/day for men. The long-term safety of such large doses has not been demonstrated, and there is the theoretical possibility that high-dose DHEA could promote the development of hormone-dependent cancers, such as breast and prostate cancer. Fortunately, doses closer to the physiological range were effective in the open-label portion of this trial, and also in some previous clinical trials, so it is probably not necessary to initiate treatment with supraphysiological doses.

DHEA does not appear to function as an antidepressant per se. However, if clinical depression is associated with DHEA deficiency, then supplementation with DHEA may be relieve the depression. As DHEA levels decline with age, it is reasonable to expect that some cases of midlife-onset depression are due to DHEA deficiency.

Schmidt PJ, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005;62:154-162.