DHEA for Depression and Schizophrenia?

I almost did not write this, because it might appear that I am promoting the use of DHEA for treatment of mental illness.  Just to be clear, I am not promoting the use of DHEA for any purpose whatsoever.  

Medscape has a couple of brief articles about the use of DHEA.  (Free registration required)  One is a report on a study of the use of DHEA for mild to moderate depression; the other is a report of a study testing DHEA for the alleviation of symptoms of schizophrenia.  The depression article offers 0.25 CME credits.

DHEA May Be Effective for Midlife-Onset Minor and Major Depression

Feb. 8, 2005 — Dehydroepiandrosterone (DHEA) can be effective for midlife-onset minor and major depression, according to the results of a placebo-controlled, randomized trial published in the February issue of the Archives of General Psychiatry.

"Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants," write Peter J. Schmidt, MD, from the National Institute of Mental Health in Rockville, Maryland, and colleagues. "The adrenal androgen and neurosteroid DHEA is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects." [...]

DHEA treatment for six weeks was associated with improvement in both primary outcome measures compared with both baseline (P < .01) and with six weeks of placebo (P < .01). After DHEA treatment, 23 subjects had a 50% or greater reduction in baseline HDRS-17 scores, as did 13 subjects after placebo treatments. DISF scores relative to baseline and placebo conditions also improved significantly after six weeks of DHEA treatment. The treatment with DHEA was well-tolerated.

The article pertaining to schizophrenia is older (2003):

DHEA Augmentation Improves Schizophrenic Symptoms

Feb. 13, 2003 — Dehydroepiandrosterone (DHEA) augmentation markedly improved negative, depressive, and anxiety symptoms in patients with schizophrenia, according to the results of a small, randomized, double-blind trial reported in the February issue of the Archives of General Psychiatry.

"In humans, DHEA has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence, and activity levels in various populations," write Rael D. Strous, MD, from the Beer Yaakov Mental Health Center in Israel, and colleagues. "The findings from this study raise important issues regarding the role of neurosteroids in general, and DHEA in particular, in the ongoing symptomatology and pharmacotherapy of schizophrenia." [...]

Why not rush to recommend DHEA for patients in the respective populations?  First of all, DHEA is metabolized to androgenic and estrogenic compounds, and may affect sex steroid-sensitive tumors.  

DHEA has the potential to cause virilization: oily skin, acne, voice deepening, and increase facial and body hair.  So it is basically a hormone treatment.  That is not to say that it should not be used, but it does mean that there are theoretical reasons to think it may have more serious adverse effects.  As was the case with hormone replacement therapy for women, it would take a large, careful study to evaluate the risk-benefit ratio.  Neither DHEA study was anywhere near large enough, nor long enough, to detect problems that would occur at a low incidence, or that would occur after a long period of treatment.

Hormones tend to be powerful drugs, and should be used with great caution.  The fact that DHEA is derived from natural sources, rather than being made in a factory, should not be taken as an indication of safety.  The fact that the FDA does not regulate the sale of DHEA, likewise, should not be taken as an indication of safety.  Furthermore, the doses used in the studies were above that which would provide a normal level of hormones.  (50mg/day restores normal levels in elderly persons.)

In the heirachy of evidence-based medicine, these two DHEA studies would be ranked rather low on the scale of validity for use in medical decision-making.  However, the two studies do show how some potential new treatments trypically are assessed early in the course of drug development.  Also, citing these studies gives me an opportunity to show why we need to be cautious when it comes to evaluating such early reports.