DHEA for Depression
Abstract & Commentary
Source: Wolkowitz OM, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Amer J Psychiatry 1999;156:646-649.
This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans. Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, re-ceived either DHEA (maximum dose = 90 mg/d) or placebo for six weeks in a double-blind manner. Assessment was repeated at baseline and at the end of the six weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone. DHEA was associated with a significantly greater decrease in Hamilton Depression Scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms. These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.
Comment by John LaPuma
The authors of this thoughtful, well-referenced pilot studyhnote that despite the epidemiological evidence for a direct relationship between DHEA and DHEA-S levels and positive mood, reports of levels in patients with major depression are inconsistent. Potential mechanisms include DHEA metabolism to testosterone and estrogen, modulation of testosterone bioavailability, and cortisol antagonism. These actions may also, of course, exacerbate hormone-mediated tumors, including breast, prostrate, uterus, and cervix.
Supported by a grant from the National Alliance for Research in Schizophrenia and Affective Disorders, these UCSF and City of Hope investigators randomized 20 unipolar and two bipolar type II patients (12 males, 10 female, mean age 44 years) to DHEA or placebo. Seven subjects (three in the DHEA group and four in the placebo group) were medication free; the others were on stable doses of antidepressants for at least two months. DHEA was given 30 mg once daily for the first two weeks, then twice daily for two weeks and then three times daily for two weeks. The dosage was chosen to give the high end of the physiological range of healthy young adults. All subjects began with a Hamilton Depression Scale score of 16 or greater.
No one dropped out because of side effects; the drug was equally effective in medication-free subjects and those continuing treatment with antidepressants. The authors note that oily skin, acne, hirsutism, and voice-deepening are reported side effects, together with anecdotal reports of significant negative mood changes.
Recommendation
DHEA for depression has real therapeutic possibilities, though its endo-crinologic effects are worrisome and not all known. Patients who want to try it should be closely monitored and should be enrolled by a research protocol. DHEA should not be recommended without better long-term data.
(Editor’s note: As with all putative antidepressants, DHEA has been associated with treatment-emergent mania and should not be used as a monotherapy for patients with bipolar disorder.
-- Lauren Marangell, MD)
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